(Hypertension. 1996;27:465-475.)
© 1996 American Heart Association, Inc.
Articles |
From the Department of Internal Medicine and Sealy Center for Molecular Science, University of Texas Medical Branch, Galveston.
Correspondence to Allan R. Brasier, 3.142 Medical Research Building, 301 University Blvd, Galveston, TX 77555-1060. E-mail abrasier%intmeds1@mhost.utmb.edu.
| Abstract |
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. These cytokines
change the abundance of two transcription factor families that bind a
single regulatory site in the angiotensinogen promoter, the
acute-phase response element. These proteins include the nuclear
factor-
B complex and the CCAAT/enhancer binding protein family.
Activation of the renin-angiotensin system, through
production of angiotensin II, results in feedback
stimulation of angiotensinogen synthesis (the "positive
feedback loop"). We have discovered that the nuclear factor-
B
transcription factor is regulated by angiotensin II, a
finding that provides a mechanism for the transcriptional component of
angiotensinogen gene synthesis in the positive feedback
loop. These studies underscore the concept that induction of the
angiotensinogen gene by diverse
physiological stimuli is mediated through changes
in the nuclear abundance of sequence-specific transcription
factors. The intracellular convergence of cytokine- and
angiotensin IIinduced signaling pathways on the nuclear
factor-
B transcription factor provides a point for "cross
talk" between angiotensin- and
cytokine-activated second messenger pathways.
Key Words: nuclear factor-
B angiotensinogen nuclear factor-IL6
| Introduction |
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Despite the close correlation between gene expression and protein secretion, the hepatocyte should not be viewed as a passive cell constitutively secreting proteins but rather as an exquisitely hormone-responsive target for the actions of circulating steroid and peptide hormones. In fact, under appropriate physiological stimuli, such as the hepatic APR, networks of inducible plasma protein genes can be activated, and different networks of genes can be silenced to respond to the anticipated physiological needs of the organism.4
Control of AGT biosynthesis is particularly relevant to the activity of the RAS. Generation of Ang I is the rate-limiting step in the formation of the potent pressor Ang II, the major effector peptide of the activated RAS. The only known glycoprotein precursor of Ang I, AGT, circulates at concentrations (0.6 µmol/L) that are rate limiting for its maximum velocity of formation within the intravascular space (the Kd of renin is 1 µmol/L).5 Conditions that alter circulating AGT concentrations therefore influence intravascular RAS activity.6 7 This idea is supported by many independent genetic and physiological studies, in which perturbations in AGT synthesis result in Ang IIdependent changes in blood pressure.6 7 8 9 10 11 12 13 14 15 Perhaps the most compelling evidence for the relationship of AGT gene expression and blood pressure is the effect of AGT gene dose on blood pressure in rodents. Gene targeting (homologous recombination) techniques to disrupt or duplicate AGT locus has allowed the generation of mice having various numbers of functional AGT alleles.10 In these mice, plasma AGT levels increase progressively in mice containing zero to four copies of the AGT locus, and concurrently a blood pressure increase of 8 mm Hg per gene copy is observed. These data provide a strong causal relationship between AGT genotypes and blood pressure.
Numerous physiological mediators have been
described that control the expression of the AGT gene; from these
observations, it becomes clear that AGT gene expression is under
coordinate developmental, tissue-specific, and hormonal control. In
rodents, where its expression has been most thoroughly investigated,
AGT is expressed widely, for example, in the brain, heart, kidney, and
adipose tissue, where its expression and processing may affect local
organ function16 17 18 (reviewed in
Reference 19). Within
these tissues, differentiating events regulate AGT expression. This
mechanism is exemplified by the robust postpartum rise in hepatic AGT
synthesis20 and by the in vitro differentiation of
preadipocytes to mature
adipocytes.21 22 23 Moreover, within
organs normally expressing AGT, AGT transcription is responsive to
diverse hormonal
mediators.16 18 24 25 These
agents
include circulating steroid hormones
(glucocorticoids,24 25 26
estrogens,27 28 and
triiodothyronine29 ); cytokine hormones, such as
interleukin-1 or
TNF-
30 31 32 33 34 35 ;
and acutely, Ang
II.36 37 38 39 40
Intravascular Ang II production,
generated as a consequence of RAS activation, regulates the synthesis
and secretion of components necessary for the first rate-limiting
step in Ang II production (Fig 1
), upregulating
AGT expression and downregulating renin secretion. Glucocorticoid
excess, estrogen administration, and the malignant phase of essential
hypertension are all associated with both elevated AGT levels and Ang
IIdependent hypertension. Understanding how these factors control AGT
synthesis is important to elucidating the pathophysiology of these
hypertensive states. Ultimately, this knowledge may yield new
therapeutic targets for blood pressure control.6 7
|
We review the mechanisms for transcriptional activation of inducible AGT gene expression, focusing on the identification of relevant transcription factors involved. Our central concept is that inducible AGT gene expression is controlled by changes in the nuclear concentration of transcription factors. The induced DNA binding proteins recognize their cis-regulatory element through modular, highly conserved domains. Once bound to DNA control regions within selected promoters, inducible transcription factors regulate the rate of transcript formation by multiple mechanisms, including changing local chromatin structure and recruiting coactivator proteins that result in productive protein-protein interactions with the basal transcription machinery.42 43 We hypothesize that transcriptional control mechanisms of the AGT promoter in hepatocytes are important controllers of RAS activity.
| Mechanisms of AGT Gene Transcription by Glucocorticoids |
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1-antitrypsin.46 49 50
The first 700 base
pairs of the rodent genes are sufficient for tissue-specific and
hormonally regulated
expression.26 32 44 51
Nuclear
run-on assays and gene-transfer studies have shown that
glucocorticoids exert their effects at the transcriptional
level.24 26 Moreover, the fact that their induction
of AGT
gene expression is dose dependent, saturable, and antagonized by the
antiglucocorticoid RU486 indicates that this transcriptional event is
indeed mediated by the
GR3 24 25 26 52
Within the first 700 base pairs of the rodent AGT gene is a
near-palindromic GRE containing the sequence 5'-AGAACATTTTGTTTC-3'
(-584 to -570, Fig 2A
). Transfection studies on
reporter genes containing AGT promoters mutated at specific sequences
indicated that GRE I is essential for glucocorticoid induction (Fig
2B
). Site-directed mutation of GRE I into a sequence that did
not
bind recombinant GR abolished glucocorticoid induction of the reporter
gene. GRE II, a hexameric "half-site" sequence located
between -472 and -477, is insufficient for glucocorticoid
induction in the absence of a functional GRE I. GRE II, however, is
required for maximal glucocorticoid inducibility of the AGT promoter
because its mutation attenuates but does not abolish glucocorticoid
induction in the presence of wild-type GRE I. Both GRE I and GRE II
bind to recombinant GR in in vitro DNA binding assays.
Multimeric GRE I or GRE II confers glucocorticoid induction
onto an inert reporter gene. On the basis of these data, we proposed a
model in which GREs in the AGT promoter are hierarchical (GRE I is a
dominant activity) and synergistic (both GREs stimulate greater than
either GRE alone). This mechanism of regulation is shared with other
liver genes, such as tyrosine aminotransferase, in which multiple GREs
function to activate tyrosine aminotransferase transcription
synergistically.54
|
A mechanism for GR induction of the AGT promoter is schematically
presented in Fig 2C
. The GR is a ligand-inducible
transcription factor maintained in an 8S-heteromeric complex within the
cytoplasm through interactions with heat-shock proteins -70,
90, and 56 (reviewed in References 53 and 55). Glucocorticoids, after
entering the cell, bind to the receptor with nanomolar affinity. Upon
binding to ligand, the 8S heteromeric GR complex disassociates into a
4S form that enters the nucleus. The transformed 4S receptor is now
competent for binding to high-affinity binding sites within the
genome. Once bound, GRs modulate gene expression through changes in
chromatin structure (eg, disruption of nucleosome spacing) and
recruitment of downstream
factors.53 56 57 Whether GR
interaction with the AGT promoter alters the chromatin structure or
facilitates the binding of downstream activators is unknown
presently and will require more detailed study.
| Mechanisms of AGT Gene Activation by Inflammation |
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and interleukin-1 are likely to be the key activators of
hepatic AGT expression, although in some in vitro conditions,
interleukin-6 can activate AGT expression.60
Surprisingly, another model of inflammation, initiated by
turpentine,35 does not uniformly induce AGT gene
expression, indicating differences in the cytokine response to
different nonspecific inducers of inflammation.
Study of AGT during the APR has provided important insights into
transcriptional control elements and DNA binding proteins that control
expression of the rat AGT gene (reviewed in References 30 and 61). One
crucial DNA control element of the AGT promoter, located between
-557 and -531 in the rat gene (5' to the transcriptional
start site) is absolutely required for cytokine induction of
AGT promoter activity. This cytokine-inducible region,
containing the dyad-symmetric sequence 5'-GTTGGGATTTCCCAAC-3', was
termed the APRE. Site-directed mutations of the rat AGT promoter
within this element completely block cytokine inducibility in
stable hepatocyte transfectants and transiently transfected
promoters.31 62 Moreover, the APRE is a
TNF-
inducible enhancer that confers TNF-
induction onto an
inert minimal promoter, indicating that it functions as a bona fide
cytokine-inducible enhancer.31 62
Enter NF-
B
The APRE functions as a cytokine-inducible
enhancer
because it is a binding site for the potent NF-
B transcription
factor complex. NF-
B is a multiprotein complex encoded by different
genes, with each product sharing a homologous 250amino acid
N-terminal DNA binding domain. These members include Rel A (p65), Rel
B, NF-
B1 (NF-
B p50), and NF-
B2 (NF-
B p49) (reviewed in
Reference 63). Rel A is a powerful transactivating NF-
B family
member by virtue of its unique COOH-terminal transactivating
domain.64 65 By contrast, NF-
B1 is an inert DNA
binding
protein representing an N-terminal proteolytic product
of a 105-kD precursor as a consequence of processing from the
ubiquitin-proteasome pathway.66 67 Rel A/NF-
B1
heterodimers have slightly different DNA binding preferences than
either protein alone, and in the appropriate cell line they are
inactivated by association with inhibitory
cytoplasmic proteins.
In resting hepatocytes, NF-
B is sequestered
in the
cytoplasm through reversible interactions with a family of
inhibitory proteins termed
I
B.68 69 70 One
I
B protein identified in rat liver is the homologue of human MAD3
(I
B
).71 I
B
binds to NF-
B1/Rel A through
repetitive, conserved domains homologous to erythrocyte ankyrin. In so
doing, I
B prevents DNA binding activity of Rel A and masks its
nuclear localization signal.72 Cytokines, such as
TNF-
, activate NF-
B by disrupting its association with
the I
B inhibitor through a coupled
phosphorylation-I
B degradation
step,67 73 74 75 allowing the
NF-
B complex to enter the
nucleus, bind to inducible promoters, and stimulate their
transcription.
Mutations of the APRE that disrupt NF-
B binding
also prevent
cytokine induction of the AGT promoter.31 62 That
the inert NF-
B1 DNA binding subunit binds to the AGT APRE in
unstimulated hepatocyte nuclei has been shown by
cross-competition using NF
B1 binding site
oligonucleotides for in vitro DNA binding assays (Fig
3
)26 32 and inclusion of NF-
B1
subunitspecific antibodies in gel mobility "supershifting"
assays (Fig 4
).62 All of these studies
demonstrate that the DNA binding activity of NF-
B1 is present in
the nuclei of unstimulated cells where APRE transcription is
low.62 After TNF-
treatment, however, the amount of
NF-
B1 bound by the APRE increases, but the transcriptionally potent
Rel A, previously undetectable, becomes a major APRE binding protein
(Figs 3
and 4
). The induction of APRE
transcription occurs in parallel
with the appearance of the NF-
B1/Rel A nucleoprotein
complex.62 Taken together, these data can be interpreted
as indicating that Rel A is the relevant APRE
transactivator in response to TNF-
treatment.
|
|
Analysis of
transiently expressed mutants of the Rel A
transactivator (expressed as a fusion protein with the
yeast GAL4 DNA binding domain) in HepG2 hepatocytes has
allowed the identification of a domain necessary for TNF-
induction
(summarized in Fig 5A
). Deletion of amino acids 1-254
blocks TNF-
induction of GAL4/Rel A 255-551 but does not inhibit its
function as a transactivator.62 These
observations indicate the requirement of amino acids 1-254 for
cytokine induction. This domain is involved in DNA binding,
interaction with I
B, nuclear localization, and dimerization and also
contains protein kinase A and PKC phosphoacceptor
sites.65 76 77 In the GAL4/Rel A chimera,
the GAL4 DNA
binding domain supplies DNA binding, nuclear localization, and
dimerization activity for the fusion protein. Thus, we believe that the
most likely mechanism for loss of TNF-
induction is that amino acids
1-254 are necessary for interaction with I
B. The deletion of the Rel
homology domain prevents sequestration of Rel A in the cytoplasm,
allowing Rel A to enter the nucleus and stimulate reporter gene
activity independently of the TNF-
hormone.
|
Recruitment of Rel A,
the NF-
B subunit with potent
transactivation properties, into the APRE/NF-
B1 complex is thus
vital to the trans-activation process. Determination of the molecular
mechanisms by which Rel A activates the AGT promoter will
require additional study. NF-
B1/Rel A stimulates the transcription
of the human immunodeficiency virus promoter in a fashion dependent on
the addition of cofactor fractions as well as the basal transcription
factors.78 Whether AGT gene activation by NF-
B1/Rel A
requires similar cofactors will require further study. In addition,
after DNA binding, Rel A bends DNA; this property may indicate that one
mechanism that Rel A uses to activate AGT gene expression is
through "looping," where the APRE could be brought into close
contact with the basal transcription machinery.
C/EBP Exchange During the APR
Analysis of APRE binding
proteins isolated from rat
hepatocytes led to the identification of a family of
heat-stable DNA binding proteins that also contact the APRE in a
sequence-specific fashion (summarized in Fig 5B
). These
proteins,
members of the C/EBP family, interact with guanosine residues distinct
from and overlapping with those bound by the NF-
B
complex.32 C/EBP
is constitutively expressed in
hepatocytes. By contrast, another C/EBP family member,
NF-IL6, is itself an acute-phaseinducible protein in
hepatocytes in which its abundance increases in response to
inflammation.80 NF-IL6 is the human homologue of
rat liverenriched transcriptional activator
protein,85 interleukin-6 DNA binding
protein,86
1 acid glycoprotein
enhancer binding protein,87 mouse C/EBPß,88
and C/EBP-related protein 2.89 Within the
NH2-terminus are stretches of alanine and proline residues
that function in cell typespecific promoter
activation.90 Moreover, NFIL6 is a protein whose
activity can be modulated by protein kinase A,82
mitogen-activated kinase,83 and
calcium-calmodulindependent kinase84
and related phosphatases by
phosphorylation/dephosphorylation
in the appropriate cell type.
At the COOH terminus of the protein lies its DNA binding domain, through which NF-IL6 recognizes the APRE by an 81-residue basic region/leucine zipper motif. We described the use of controlled tryptic protease digestion of recombinant NF-IL6/APRE complex to identify the core DNA binding domain.79 Within the basic region/leucine zipper DNA binding domain lies a stretch of six amino acids whose deletion markedly destabilizes the DNA complex, termed the complex stabilizing subdomain.79
The precise role of the C/EBPs in
regulating AGT expression has
remained elusive, particularly because of the lack of suitable in vitro
models for their study. In vitro DNA binding assays demonstrate that
the NF-
B1/Rel A protein and C/EBPs bind to the APRE in a mutually
exclusive manner.32 61 In unstimulated
hepatocytes, in which the C/EBPs are less potent
transactivators than Rel A, C/EBP members function as
competitive inhibitors of Rel A activity by virtue of
displacing the more potent transactivator.
Nevertheless, this observation is of uncertain relevance to the
biological situation of the hepatic APR because potential signals that
modify NF-IL6 activity may not be present. Several clues indicate
the potential importance of the C/EBPs for AGT expression. First, the
C/EBPs are expressed in high abundance in both hepatocytes
and adipocytes. On a weight basis, both of these tissues produce the
highest levels of AGT mRNA. Second, that C/EBP
, the most potent APRE
transactivator of the C/EBP family, is first expressed
in rodent liver immediately postpartum91 at a time when
AGT synthesis can first be detected20 perhaps suggests its
role in constitutive AGT gene expression during development. Moreover,
in hepatocytes and adipocytes, cytokine stimulation
produces a fall in the constitutive C/EBP
and a slower increase in
NF-IL6 protein.23 92 During this exchange of C/EBPs,
a
"window" may be opened for the NF-
B transcription factor to
access the APRE during the APR.
In summary, circulating cytokines
secreted from
activated macrophages are effectors of the highly
conserved APR in vertebrates. The cytokines interleukin-1 and
TNF-
bind to specific hepatocyte receptors, activating
second messenger signaling cascades that ultimately control the nuclear
expression of the two transcription factor families that bind to the
APRE. Rel A/NF-
B1 is a transcription factor complex that, like the
GR, is a preformed complex in the cytoplasm associated with
inhibitory proteins (I
B). Rel A/NF-
B1 is released
from the inhibitor in response to cytokine
signaling events, allowing Rel A/NF-
B1 to translocate into the
nucleus and stimulate transcription. A schematic model for the
mechanism of AGT gene expression during the APR is presented in
Fig 5C
.
| Transcriptional Mechanism of the RAS Positive Feedback Loop |
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The identification of the cis-regulatory element(s) and
corresponding trans-acting factor(s) mediating the positive
feedback loop on AGT gene synthesis has remained elusive. One
difficulty in studying Ang IIdependent enhancers has been the loss of
normally expressed AT1 receptor expression after isolation
of primary hepatocytes and the lack of AT1
expression in transformed hepatocyte
cultures.96 The molecular cloning of AT1 has
led to the development of an important reagent to address the mechanism
of the RAS positive feedback loop.97 Transient
high-level expression of AT1 results in
high-affinity Ang II binding activity that is functionally coupled
to intracellular calcium transients.97 Using transcription
assays in AT1-complemented human hepatocytes,
we have shown that the AGT multihormonal response element, spanning
nucleotides -615 to -470, is an Ang
IIinducible enhancer.96 Transcription driven by the
multihormone-inducible enhancer occurs over a
physiological dose-responsive range producing a
statistically significant threefold induction that peaks at a
concentration of 10 nmol/L Ang II (identical to the
Kd of AT1).97 Mutations
of the multihormone-inducible enhancer that blocks NF-
B binding
also abolished Ang II induction of the transfected AGT
transgenes.96 The APRE is an Ang IIinducible enhancer
because it confers Ang II inducibility onto an inert promoter driving
the luciferase reporter (Fig 6
and Reference 96). The
Ang IIinducible APRE activity was first detectable at 0.01 nmol/L Ang
II, with the maximal 13-fold induction seen in response to 10 nmol/L
Ang II. Higher doses of up to 100 nmol/L gave less activity than the
maximum 13-fold, perhaps because of the well-described phenomenon
of agonist-induced receptor downregulation.99
Importantly, the fact that the Ang IIdependent transcriptional
activation was seen only in cells cotransfected with the
AT1 expression vector indicates that AT1 is
absolutely required for this effect.96 As with the
site-directed mutations within the native AGT
multihormone-inducible enhancer, Ang II stimulation of the APRE
depends on NF-
B binding because no transcriptional induction by Ang
II was seen in either APRE M6 (a mutant that binds C/EBP only) or APRE
M2 (a mutant that binds neither NF-
B nor C/EBP) driving the
luciferase reporter gene in response to Ang II.
|
Continuously perfused primary hepatocytes have been used to
demonstrate that Ang II induces AGT mRNA and protein.40
With the gel mobility shift assay, a fourfold increase of APRE binding
activity by Ang II was observed in a dose-dependent fashion. First
detectable at 0.5 nmol/L Ang II, APRE binding activity peaks at a
physiological concentration of 5 nmol/L Ang II.
Continuous infusion of 50 nmol/L Ang II produced no greater
stimulation, so the effect of Ang II is saturable. This
concentration range is indistinguishable from that required for
transcriptional activity in transient HepG2 transfectants. Moreover,
the increase in APRE DNA binding activity was rapid and observed as
early as 1 hour after stimulation. Competition analysis showed
that Ang IIactivated APRE binding is sequence specific for
the NF-
B protein family. The Rel A transcriptional
activator was identified in this complex with
subunit-specific antibodies in the gel mobility "supershift"
assay.
Ang II and TNF-
Induced Signals Are Convergent on
NF-
B Rel
A
The finding that Ang II and TNF-
activate Rel A
indicates that in some cells (such as hepatocytes),
postreceptor cytokine and cardioactive peptide signaling
pathways are convergent (Fig 7
). In a wide variety
of cell types, TNF-
activates NF-
B through two
mechanisms: (1) a phosphatidylcholine-specific phospholipase
Ccoupled activation of an acidic sphingomyelinase with formation
of ceramide as a second messenger, and (2) 1,2-diacylglycerol formation
resulting from PKC
activation.98 99 100 101
Either of these
pathways appears to be sufficient to induce the proteolysis of I
B
through a coupled phosphorylation/degradation
pathway.
|
In contrast, on binding to the hepatocyte type 1 receptor,
Ang II stimulates the formation of 1,2-diacylglycerol with consequent
PKC activation, mobilization of intracellular calcium, and inhibition
of hormone-stimulated adenylate cyclase
activity.97 99 102 103 Of
these, PKC appears to be an
important molecule for Ang II to induce early gene (c-fos)
synthesis. Chronic exposure to phorbol agonist (to downregulate PKC)
completely inhibits c-fos induction in
cardiomyocytes104 and partly antagonizes
c-fos induction in glomerulosa cells105 or
vascular smooth muscle cells.106 Although the relevant
signaling events activated by Ang II that control NF-
B
activity remain speculative, the demonstration that certain PKC
isoforms are physically associated with the I
B molecule (kinases
that can phosphorylate and inactivate this
inhibitor in vitro107 ) makes PKC a likely
candidate for coupling the activated AT1 receptor
to modulating NF-
B activity.
We note the recently reported observations in vascular smooth muscle cells that AT1 receptor is functionally coupled to a distinct cytoplasmic-inducible transcription factor family (the Jak/STAT pathway).108 Although this pathway has not been implicated in AGT regulation, these observations provide additional pathways for cytokine and Ang II intracellular "cross talk" linked through the activated Ang II receptor.
Ang II and TNF-
Activate Rel A Through Pharmacologically
Distinct Intracellular Signaling Pathways
Although the rapid induction
of Rel A DNA binding and
transcriptional activity by Ang II is similar to the kinetics of Rel A
activation by TNF-
reported in our earlier studies,62
we consistently observed that Ang II was a less-potent APRE
stimulus than TNF-
, perhaps indicating that these agents were acting
through different intracellular messengers. We therefore used transient
transfection assays to determine whether Ang II and TNF-
were
activating APRE transcription via similar or distinct intracellular
signals. Both Ang II and TNF-
induction of APRE-luciferase reporter
activity are critically dependent on the activity of the
phosphatidylcholine-specific phospholipase C because the specific
phosphatidylcholine-specific phospholipase C inhibitor
tricyclodecan-9-yl xanthogenate (D609) completely blocks reporter
induction by either hormone (data not shown).100 104
In
contrast, the induction by Ang II of luciferase reporter activity was
completely blocked by the protein kinase inhibitor
staurosporine (50 nmol/L), and TNF-
induction was
unaffected at the same inhibitor concentrations (Fig 6B
).
In addition, chronic agonist downregulation of PKC activity also
completely blocked the effect of Ang II but only partially affected the
activity of TNF-
on APRE-luciferase reporter activity (Fig
6C
).
Taken together, these data indicate the existence of
pharmacologically distinct second messenger pathways by which Ang II
and TNF-
activate APRE transcription.
| Summary |
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and interleukin-1) and the vasoactive Ang II peptide produce AGT
transcription through a distinct cytoplasmically inducible
transcription factor composed of the NF-
B subunit NF-
B1/Rel A.
NF-
B1, the inert DNA binding subunit, is found in nuclei from
unstimulated cells. Recruitment of the potent transcriptionally active
Rel A subunit is necessary for AGT promoter induction. This process
occurs through a signal-induced
phosphorylation/I
B degradation step, resulting in
nuclear translocation of the Rel A DNA binding activity. Finally, our
present data indicate that the cytokine TNF-
and the
vasopressor Ang II converge on Rel A activator but do so
through a pharmacologically distinct pathway (Fig 7| Selected Abbreviations and Acronyms |
|---|
|
| Acknowledgments |
|---|
| References |
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2. Cassio D, Weiss MC, Ott M-O, Sala-Trepat JM, Fries J, Erdos T. Expression of the albumin gene in rat hepatoma cells and their dedifferentiated variants. Cell. 1981;27:351-358. [Medline] [Order article via Infotrieve]
3. Coezy E, Bouhnik J, Clauser E, Pinet F, Philippe M, Menard J, Corvol P. Effects of glucocorticoids and antiglucocorticoids on angiotensinogen production by hepatoma cells in culture. In Vitro. 1984;20:528-534. [Medline] [Order article via Infotrieve]
4.
Birch H, Schreiber G. Transcriptional
regulation of plasma protein synthesis during
inflammation. J Biol Chem. 1986;261:8077-8080.
5. Reid IA, Morris BJ, Ganong WG. The renin-angiotensin system. Annu Rev Physiol. 1978;40:377-410. [Medline] [Order article via Infotrieve]
6.
Peach MJ. Renin-angiotensin
system: biochemistry and mechanisms of action. Physiol
Rev. 1977;57:313-370.
7.
Krakoff LR. Measurement of plasma-renin
substrate by radioimmunoassay of angiotensin, I:
concentration in syndromes associated with steroid excess.
J Clin Endocrinol Metab. 1973;37:110-117.
8.
Walker WG, Whelton PK, Saito H, Russel RP, Hermann
J. Relation between blood pressure and renin, renin substrate,
Ang II, aldosterone and urinary sodium and potassium in 574
ambulatory subjects. Hypertension. 1979;1:287-291.
9. Jeunemaitre X, Soubrier F, Kotelevtsev YV, Lifton RP, Williams CS, Charru A, Hunt SC, Hopkins PN, Williams RR, Lalouel JM, Corvol P. Molecular basis of human hypertension: role of angiotensinogen. Cell. 1992;71:169-180. [Medline] [Order article via Infotrieve]
10.
Kim HS, Krege JH, Kluckman KD, Hagaman JR, Hodgin JB,
Best CF, Jennette JC, Coffman TM, Maeda N, Smithies O. Genetic
control of blood pressure and the angiotensinogen
locus. Proc Natl Acad Sci U S A. 1995;92:2735-2739.
11. Campbell DJ, Rong P, Kladis A, Rees B, Ganten D, Skinner SL. Angiotensin and bradykinin peptides in the TGR (mRen-2) 27 rat. J Hypertens. 1995;25:1014-1020.
12.
Tanimoto K, Sugiyama F, Goto Y, Ishida J, Takimoto E,
Yagami K, Fukamizu A, Murakami K.
Angiotensinogen-deficient mice with
hypotension. J Biol Chem. 1994;269:31334-31337.
13. Kimura S, Mullins JJ, Bunnemann B, Metzger R, Hilgenfeldt U, Zimmermann F, Jacob H, Fuxe K, Ganten D, Kaling M. High blood pressure in transgenic mice carrying the rat angiotensinogen gene. EMBO J. 1992;11:821-827. [Medline] [Order article via Infotrieve]
14.
Ohkubo H, Kawakami H, Kakehi Y, Takumi T, Arai H,
Yokota Y, Iwai M, Tanabe Y, Masu M, Hata J, Iwao H. Generation
of transgenic mice with elevated blood pressure by introduction of rat
renin and angiotensinogen genes. Proc Natl
Acad Sci U S A. 1990;87:5153-5157.
15.
Caulfield M, Lavender P, Farrall M, Munroe P, Lawson
M, Turner P, Clark AJ. Linkage of the
angiotensinogen gene to essential hypertension.
N Engl J Med. 1994;330:1629-1633.
16. Campbell DJ, Habener JF. Angiotensinogen gene is expressed and differentially regulated in multiple tissues of the rat. J Clin Invest. 1986;78:31-39.
17.
Cassis LA, Saye J, Peach MJ. Localization and
regulation of rat angiotensinogen messenger RNA.
Hypertension. 1988;11:591-596.
18. Klett C, Hellmann W, Hackenthal E, Ganten D. Modulation of tissue angiotensinogen gene expression by glucocorticoids, estrogens, and androgens in SHR and WKY rats. Clin Exp Hypertens. 1993;15:683-708.
19. Campbell DJ. Circulating and tissue angiotensin systems. J Clin Invest. 1987;79:1-6.
20.
Gomez RA, Cassis L, Lynch KR, Chevalier RL, Wilfong
N, Carey RM, Peach MJ. Fetal expression of the
angiotensinogen gene. Endocrinology. 1988;123:2298-2302.
21.
Tamura K, Umemura S, Iwamoto T, Yamaguchi S,
Kobayashi S, Takeda K, Tokita Y, Takagi N, Murakami K, Fukamizu
A. Molecular mechanism of adipogenic activation of the
angiotensinogen gene.
Hypertension. 1994;23:364-368.
22.
McGehee RE Jr, Ron D, Brasier AR, Habener JF.
Differentiation-specific element: a cis-acting developmental
switch required for the sustained transcriptional expression of the
angiotensinogen gene during hormonal-induced
differentiation of 3T3-L1 fibroblasts to adipocytes. Mol
Endocrinol. 1993;7:551-560.
23. Ron D, Brasier AR, McGehee RE Jr, Habener JF. Tumor necrosis factor-induced reversal of adipocytic phenotype of 3T3-L1 cells is preceded by a loss of nuclear CCAAT/enhancer binding protein (C/EBP). J Clin Invest. 1992;89:223-233.
24.
Brasier AR, Philippe J, Campbell DJ, Habener
JF. Novel expression of the angiotensinogen gene in
a rat pancreatic islet cell line: transcriptional regulation by
glucocorticoids. J Biol Chem. 1986;261:16148-16154.
25.
Kalinyak JE, Perlman AJ. Tissue-specific
regulation of angiotensinogen mRNA accumulation by
dexamethasone. J Biol Chem. 1987;262:460-464.
26.
Brasier AR, Ron D, Tate JE, Habener JF.
Synergistic enhansons located within an acute phase responsive enhancer
modulate glucocorticoid induction of angiotensinogen gene
transcription. Mol Endocrinol. 1990;4:1921-1933.
27. Krattenmacher R, Knauthe R, Parczyk K, Walker A, Hilgenfeldt U, Fritzemeier KH. Estrogen action on hepatic synthesis of angiotensinogen and IGF-I: direct and indirect estrogen effects. J Steroid Biochem. 1994;48:207-214.
28. Gordon MS, Chin WW, Shupnik MA. Regulation of angiotensinogen gene expression by estrogen. J Hypertens. 1992;10:361-366. [Medline] [Order article via Infotrieve]
29.
Hong-Brown LQ, Deschepper CF. Effects of
thyroid hormones on angiotensinogen gene expression in rat
liver, brain, and cultured cells. Endocrinology. 1992;130:1231-1237.
30. Ron D, Brasier AR, Habener JF. Transcriptional regulation of hepatic angiotensinogen gene expression by the acute-phase response. Mol Cell Endocrinol. 1990;74:C97-C104. [Medline] [Order article via Infotrieve]
31.
Ron D, Brasier AR, Wright KA, Tate JE, Habener
JF. An inducible 50-kilodalton NF kappa B-like protein and a
constitutive protein both bind the acute-phase response element of
the angiotensinogen gene. Mol Cell Biol. 1990;10:1023-1032.
32. Brasier AR, Ron D, Tate JE, Habener JF. A family of constitutive C/EBP-like DNA binding proteins attenuate the IL-1 alpha induced, NF kappa B mediated trans-activation of the angiotensinogen gene acute-phase response element. EMBO J. 1990;9:3933-3944. [Medline] [Order article via Infotrieve]
33.
Ron D, Brasier AR, Wright KA, Habener JF. The
permissive role of glucocorticoids on interleukin-1 stimulation of
angiotensinogen gene transcription is mediated by an
interaction between inducible enhancers. Mol Cell
Biol. 1990;10:4389-4395.
34. Kageyama R, Ohkubo H, Nakanishi S. Induction of rat liver angiotensinogen mRNA following acute inflammation. Biochem Biophys Res Commun. 1985;129:826-832. [Medline] [Order article via Infotrieve]
35. Bouhnik J, Savoie F, Corvol P. Differential effects of inflammation models on rat T-kininogen and rat angiotensinogen. Biochem Pharmacol. 1988;37:1099-1102. [Medline] [Order article via Infotrieve]
36.
Kohara K, Brosnihan KB, Ferrario CM, Milsted
A. Peripheral and central angiotensin II
regulates expression of genes of the renin-angiotensin
system. Am J Physiol. 1992;262:E651-E657.
37.
Eggena P, Zhu JH, Clegg K, Barrett JD. Nuclear
angiotensin receptors induce transcription of renin and
angiotensinogen mRNA.
Hypertension. 1993;22:496-501.
38.
Hilgenfeldt U, Schwind S.
Angiotensin II is the mediator of the increase in hepatic
angiotensinogen synthesis after bilateral
nephrectomy. Am J Physiol. 1993;265:E414-E418.
39.
Nakamura A, Iwao H, Fukui K, Kimura S, Tamaki T,
Nakanishi S, Abe Y. Regulation of liver
angiotensinogen and kidney renin mRNA levels by
angiotensin II. Am J Physiol. 1990;258:E1-E6.
40.
Klett C, Nobiling R, Gierschik P, Hackenthal
E. Angiotensin II stimulates the synthesis of
angiotensinogen in hepatocytes by inhibiting
adenylylcyclase activity and stabilizing angiotensinogen
mRNA. J Biol Chem. 1993;268:25095-25107.
41. Shade RE, Davis JO, Johnson JA, Gotshall RW, Spielman WS. Mechanism of action of angiotensin II and antidiuretic hormone on renin secretion. Am J Physiol. 1973;224:926-943.
42. Tjian R, Maniatis T. Transcriptional activation: a complex puzzle with few easy pieces. Cell. 1994;77:5-8. [Medline] [Order article via Infotrieve]
43. Wolffe AP. Transcription: in tune with the histones. Cell. 1994;77:13-16. [Medline] [Order article via Infotrieve]
44. Clouston WM, Lyons IG, Richards RI. Tissue-specific and hormonal regulation of angiotensinogen minigenes in transgenic mice. EMBO J. 1989;8:3337-3343. [Medline] [Order article via Infotrieve]
45. Clauser E, Bouhnik J, Jaramillo HN, Auzan C, Corvol P, Menard J. Angiotensinogen production and consumption in the adrenalectomized rat. Endocrinology. 1985;116:247-280.
46.
Tanaka T, Ohkubo H, Nakanishi S. Common
structural organization of the angiotensinogen and the
alpha-1 antitrypsin genes. J Biol Chem. 1984;259:8063-8065.
47.
Ohkubo H, Nakayama K, Tanaka T, Nakanishi S.
Tissue distribution of rat angiotensinogen mRNA and
structural analysis of its
heterogeneity. J Biol
Chem. 1986;261:319-323.
48. Clouston WM, Evans LA, Haralambidis J, Richards RI. Molecular cloning of the mouse angiotensinogen gene. Genomics. 1988;2:240-248. [Medline] [Order article via Infotrieve]
49. Gaillard I, Clauser E, Corvol P. Structure of human angiotensinogen gene. DNA. 1989;8:87-99. [Medline] [Order article via Infotrieve]
50.
Doolittle RF. Angiotensinogen is
related to the antitrypsin-antithrombin-ovalbumin
family. Science. 1983;222:417-419.
51.
Brasier AR, Tate JE, Ron D, Habener JF.
Multiple cis-acting DNA regulatory elements mediate hepatic
angiotensinogen gene expression. Mol
Endocrinol. 1989;3:1022-1034.
52.
Ben-Ari ET, Lynch KR, Garrison JC.
Glucocorticoids induce the accumulation of novel
angiotensinogen gene transcripts. J
Biol Chem. 1989;264:13074-13079.
53. Beato M. Gene regulation by steroid hormones. Cell. 1989;56:335-344. [Medline] [Order article via Infotrieve]
54. Jantzen HM, Strahle U, Gloss B, Stewart F, Schmid W, Boshart M, Miksicek R, Schutz G. Cooperativity of glucocorticoid response elements located far upstream of the tyrosine aminotransferase gene. Cell. 1987;49:29-38. [Medline] [Order article via Infotrieve]
55. Pratt WB. The role of heat shock proteins in regulating the function, folding, and trafficking of the glucocorticoid receptor. J Biol Chem. 1994;268:21445-21458.
56.
Archer TK, Lefebvre P, Wolford RG, Hager GL.
Transcription factor loading on the MMTV promoter: a bimodal mechanism
for promoter activation. Science. 1992;255:1573-1576.
57. Pina B, Bruggemeier U, Beato M. Nucleosome positioning modulates accessibility of regulatory proteins to the mouse mammary tumor virus promoter. Cell. 1990;60:719-731. [Medline] [Order article via Infotrieve]
58. Hoj Nielsen A, Knudsen F. Angiotensinogen is an acute-phase protein in man. Scand J Clin Lab Invest. 1987;47:175-178. [Medline] [Order article via Infotrieve]
59. Okamoto H, Hatta A, Itoh N, Ohashi Y, Arakawa K, Nakanishi S. Acute phase responses of plasma angiotensinogen and T-kininogen in rats. Biochem Pharmacol. 1987;36:3069-3073. [Medline] [Order article via Infotrieve]
60. Takano M, Itoh N, Yayama K, Yamano M, Ohtani R, Okamoto H. Interleukin-6 as a mediator responsible for inflammation-induced increase in plasma angiotensinogen. Biochem Pharmacol. 1993;45:201-206. [Medline] [Order article via Infotrieve]
61. Brasier AR, Li J, Copland A. Transcription factors modulating angiotensinogen gene expression in hepatocytes. Kidney Int. 1994;46:1564-1566. [Medline] [Order article via Infotrieve]
62. Brasier AR, Li J, Wimbish KA. Tumor necrosis factor activates angiotensinogen gene expression by the Rel A transactivator. Hypertension. In press.
63. Baeuerle PA. The inducible transcription activator NF-kappa B: regulation by distinct protein subunits. Biochim Biophys Acta. 1991;1072:63-80. [Medline] [Order article via Infotrieve]
64.
Schmitz ML, Baeuerle PA. The p65 subunit is
responsible for the strong transcription activating potential of
NF-
B. EMBO J. 1991;12:3805-3817.
65.
Ruben SM, Narayanan R, Klement JF, Chen CH, Rosen
CA. Functional characterization of the NF-kappa B p65
transcriptional activator and an alternatively spliced
derivative. Mol Cell Biol. 1992;12:444-454.
66. Blank V, Kourilsky P, Israel A. NF-kappa B and related proteins: Rel/dorsal homologies meet ankyrin-like repeats. Trends Biochem Sci. 1992;17:135-140. [Medline] [Order article via Infotrieve]
67.
Palombella VJ, Rando OJ, Goldberg AL, Maniatis
T. The ubiquitin-proteasome pathway is required for
processing the NF-
B1 precursor protein and the activation of
NF-
B. Cell. 1994;78:773-785. [Medline]
[Order article via Infotrieve]
68.
Urban MB, Baeuerle PA. The 65-kD subunit of
NF-kappa B is a receptor for I kappa B and a modulator of DNA-binding
specificity. Genes Dev. 1990;4:1975-1984.
69.
Baeuerle PA, Baltimore D. A 65-kDa subunit of
active NF-kappaB is required for inhibition of NF-
B by I
B.
Genes Dev. 1989;3:1689-1698.
70.
Beg AA, Baldwin AS Jr. The I kappa B proteins:
multifunctional regulators of Rel/NF-kappa B transcription
factors. Genes Dev. 1993;7:2064-2070.
71.
Tewari M, Dobrzanski P, Mohn KL, Cressman DW, Hsu
J-C, Bravo R, Taub R. Rapid induction in regenerating liver of
RL/IF-1 (an I
B that inhibits NF-
B, RelB-p50, and c-Rel-p50)
and PHF, a novel
B site-binding complex. Mol Cell
Biol. 1992;12:2898-2908.
72.
Hatada EN, Naumann M, Scheidereit C. Common
structural constituents confer I
B activity to NF-
B p105 and
I
B/MAD-3. EMBO J. 1993;12:2781-2788. [Medline]
[Order article via Infotrieve]
73.
Brown K, Gerstberger S, Carlson L, Franzoso G,
Siebenlist U. Control of I
B-alpha proteolysis by
site-specific, signal-induced
phosphorylation. Science. 1995;267:1485-1488.
74. Henkel T, Machleidt T, Alkalay I, Kronke M, Ben-Neriah Y, Baeuerle PA. Rapid proteolysis of I kappa B-alpha is necessary for activation of transcription factor NF-kappa B. Nature. 1993;365:182-185. [Medline] [Order article via Infotrieve]
75.
Lin Y-C, Brown K, Siebenlist U. Activation of
NF-
B requires proteolysis of the inhibitor I
B-
:
signal-induced phosphorylation of I
B-
alone
does not release active NF-
B. Proc Natl Acad Sci
U S A. 1995;92:552-556.
76.
Naumann M, Scheidereit C. Activation of
NF-
B in vivo is regulated by multiple
phosphorylations. EMBO J. 1994;13:4597-4607. [Medline]
[Order article via Infotrieve]
77.
Ruben SM, Dillon PJ, Schreck R, Henkel T, Chen CH,
Maher M, Baeuerle PA, Rosen CA. Isolation of a rel-related
human cDNA that potentially encodes the 65-kD subunit of NF-kappa
B. Science. 1991;251:1490-1493.
78.
Kretzschmar M, Meisterernst M, Scheidereit C, Li G,
Roeder RG. Transcriptional regulation of the HIV-1 promoter by
NF-kappa B in vitro. Genes Dev. 1992;6:761-774.
79.
Brasier AR, Kumar A. Identification of a novel
determinant for basic domain-leucine zipper (bZIP) DNA-binding
activity in the acute-phase inducible nuclear
factor-interleukin 6 transcription factor. J
Biol Chem. 1994;269:10341-10351.
80. Akira S, Isshiki H, Sugita T, Tanabe O, Kinoshita S, Nishio Y, Nakajima T, Hirano T, Kishimoto T. A nuclear factor for IL-6 expression (NF-IL6) is a member of a C/EBP family. EMBO J. 1990;9:1897-1906. [Medline] [Order article via Infotrieve]
81.
Nerlov C, Ziff EB. Three levels of functional
interaction determine the activity of CCAAT/enhancer binding
protein-alpha on the serum albumin promoter.
Genes Dev. 1994;8:350-362.
82. Trautwein C, van der Geer P, Karin M, Hunter T, Chojkier M. Protein kinase A and C site-specific phosphorylations of LAP (NF-IL6) modulate its binding affinity to DNA recognition elements. J Clin Invest. 1994;93:2554-2561.
83.
Nakajima T, Kinoshita S, Sasagawa T, Sasaki K, Naruto
M, Kishimoto T, Akira S. Phosphorylation at
threonine-235 by a ras-dependent mitogen-activated
protein kinase cascade is essential for transcription factor
NF-IL6. Proc Natl Acad Sci U S A. 1993;90:2207-2211.
84.
Wegner M, Cao Z, Rosenfeld MG.
Calcium-regulated phosphorylation within the
leucine zipper of C/EBP beta. Science. 1992;256:370-373.
85.
Descombes P, Chojkier M, Lichtsteiner S, Falvey E,
Schibler U. LAP, a novel member of the C/EBP gene family,
encodes a liver-enriched transcriptional activator
protein. Genes Dev. 1990;4:1541-1551.
86. Poli V, Mancini FP, Cortese R. IL-6DBP, a nuclear protein involved in interleukin-6 signal transduction, defines a new family of leucine zipper proteins related to C/EBP. Cell. 1990;63:643-653. [Medline] [Order article via Infotrieve]
87.
Chang CJ, Chen T-T, Lei H-Y, Chen D-S, Lee
S-C. Molecular cloning of a transcription factor, AGP/EBP, that
belongs to members of the C/EBP family. Mol Cell
Biol. 1990;10:6642-6653.
88.
Cao Z, Umek RM, McKnight SL. Regulated
expression of three C/EBP isoforms during adipose conversion of 3T3-L1
cells. Genes Dev. 1991;5:1538-1552.
89.
Williams SC, Cantwell CA, Johnson PF. A family
of C/EBP-related proteins capable of forming covalently linked leucine
zipper dimers in vitro. Genes Dev. 1991;5:1553-1567.
90. Williams SC, Baer M, Dillner AJ, Johnson PF. CRP (C/EBPß) contains a bipartite regulatory domain that controls transcriptional activation, DNA binding and cell specificity. EMBO J. 1995;14:3170-3183. [Medline] [Order article via Infotrieve]
91.
Birkenmeier EH, Gwynn B, Howard S, Jerry J, Gordon
JI, Landschulz WH, McKnight SL. Tissue-specific expression,
developmental regulation, and genetic mapping of the gene encoding
CCAAT/enhancer binding protein. Genes Dev. 1989;3:1146-1156.
92. Isshiki H, Akira S, Sugita T, Nishio Y, Hashimoto S, Pawlowski T, Suematsu S, Kishimoto T. Reciprocal expression of NF-IL6 and C/EBP in hepatocytes: possible involvement of NF-IL6 in acute phase protein gene expression. New Biol. 1991;3:63-70. [Medline] [Order article via Infotrieve]
93. Schutze S, Potthoff K, Machleidt T, Berkovic D, Wiegmann K, Kronke M. TNF activates NF-kappa B by phosphatidylcholine-specific phospholipase C-induced `acidic' sphingomyelin breakdown. Cell. 1992;71:765-776. [Medline] [Order article via Infotrieve]
94. Morishita R, Higaki J, Okunishi H, Tanaka T, Ishii K, Nagano M, Mikami H, Ogihara T, Murakami K, Miyazaki M. Changes in gene expression of the renin-angiotensin system in two kidney, one clip hypertensive rats. J Hypertens. 1991;9:187-192. [Medline] [Order article via Infotrieve]
95. Gahnem F, Camargo MJ, von Lutterotti N, Laragh JH, Sealy JE. Angiotensinogen depletion by high renin levels in hypertensive rats: no evidence for tonic stimulation of angiotensinogen by angiotensin II. J Hypertens. 1995;13:91-96. [Medline] [Order article via Infotrieve]
96.
Li J, Brasier AR. Angiotensinogen
gene activation by Ang II is mediated by the Rel A (NF-
B p65)
transcription factor: one mechanism for the renin
angiotensin system (RAS) positive feedback loop in
hepatocytes. Mol Endocrinol. In press.
97. Murphy TJ, Alexander RW, Griendling KK, Runge MS, Bernstein KE. Isolation of a cDNA encoding the vascular type-1 angiotensin II receptor. Nature. 1991;351:233-236. [Medline] [Order article via Infotrieve]
98.
Meichle A, Schutze S, Hensel G, Bruming D, Kronke
M. Protein kinase C-independent activation of NF-
B by
TNF. J Biol Chem. 1990;265:8339-8343.
99.
Bouscarel B, Blackmore PF, Exton JH.
Characterization of the angiotensin II receptor in primary
cultures of rat hepatocytes. J Biol
Chem. 1988;263:14913-14919.
100. Wiegmann K, Schutze S, Machleidt T, Witte D, Kronke M. Functional dichotomy of neutral and acidic sphingomyelinases in TNF signalling. Cell. 1994;78:1005-1015. [Medline] [Order article via Infotrieve]
101.
Wiegmann K, Schutze S, Kampen E, Himmler A, Machleidt
T, Kronke M. Human 55 kDa receptor for tumor necrosis factor
coupled to signal transduction cascades. J Biol
Chem. 1992;267:17997-18001.
102.
Griendling KK, Rittenhouse SE, Brock TA, Ekstein LS,
Gimbrone MA Jr, Alexander RW. Sustained diacylglycerol formation
from inositol phospholipids in angiotensin II-stimulated
vascular smooth muscle cells. J Biol Chem. 1986;261:5901-5906.
103.
Lang U, Valloton MB. Angiotensin II
but not potassium induces subcellular redistribution of protein kinase
C in bovine adrenal glomerulosa cells. J Biol
Chem. 1987;262:8047-8050.
104.
Sadoshima J-I, Izumo S. Signal transduction
pathways of angiotensin IIinduced c-fos gene
expression in cardiac myocytes in vitro: roles of
phospholipid-derived second messengers.
Circ Res. 1993;73:424-438.
105.
Clark AJ, Balla T, Jones MR, Catt KJ.
Stimulation of early gene expression by angiotensin II in
bovine adrenal glomerulosa cells: roles of calcium and protein kinase
C. Mol Endocrinol. 1992;6:1889-1898.
106.
Taubman MB, Berk BC, Izumo S, Tsuda T, Alexander RW,
Nadal Ginard B. Angiotensin II induces c-fos
mRNA in aortic smooth muscle: role of Ca2+ mobilization and
protein kinase C activation. J Biol Chem. 1989;264:526-530.
107.
Diaz-Meco MT, Dominguez I, Sanz L, Dent P, Lozano J,
Municio MM, Berrn E, Hay RT, Sturgill TW, Moscat J. epsilonPKC
induces phosphorylation and inactivation of I
B
in
vitro. EMBO J. 1994;13:2842-2848. [Medline]
[Order article via Infotrieve]
108. Marrero MB, Schieffer B, Paxton WG, Heerdt L, Berk BC, Delafontaine P, Bernstein KE. Direct stimulation of Jak/STAT pathway by the angiotensin II AT1 receptor. Nature. 1995;375:247-250.[Medline] [Order article via Infotrieve]
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H. KOBORI, L. M. HARRISON-BERNARD, and L. G. NAVAR Expression of Angiotensinogen mRNA and Protein in Angiotensin II-Dependent Hypertension J. Am. Soc. Nephrol., March 1, 2001; 12(3): 431 - 439. [Abstract] [Full Text] |
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L G. Navar, K. D Mitchell, L. M Harrison-Bernard, H. Kobori, and A. Nishiyama Review: Intrarenal angiotensin II levels in normal and hypertensive states Journal of Renin-Angiotensin-Aldosterone System, March 1, 2001; 2(1_suppl): S176 - S184. [PDF] |
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G. Zalba, G. S. Jose, F. J. Beaumont, M. A. Fortuno, A. Fortuno, and J. Diez Polymorphisms and Promoter Overactivity of the p22phox Gene in Vascular Smooth Muscle Cells From Spontaneously Hypertensive Rats Circ. Res., February 2, 2001; 88(2): 217 - 222. [Abstract] [Full Text] [PDF] |
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H. Schmidt, F. Fazekas, G. M. Kostner, C. M. van Duijn, and R. Schmidt Angiotensinogen Gene Promoter Haplotype and Microangiopathy-Related Cerebral Damage : Results of the Austrian Stroke Prevention Study Stroke, February 1, 2001; 32(2): 405 - 412. [Abstract] [Full Text] [PDF] |
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Y. Ding and C. D. Sigmund Androgen-dependent regulation of human angiotensinogen expression in KAP-hAGT transgenic mice Am J Physiol Renal Physiol, January 1, 2001; 280(1): F54 - F60. [Abstract] [Full Text] [PDF] |
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M. Ruiz-Ortega, O. Lorenzo, M. Ruperez, S. Konig, B. Wittig, and J. Egido Angiotensin II Activates Nuclear Transcription Factor {kappa}B Through AT1 and AT2 in Vascular Smooth Muscle Cells : Molecular Mechanisms Circ. Res., June 23, 2000; 86(12): 1266 - 1272. [Abstract] [Full Text] [PDF] |
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M. Ruiz-Ortega, O. Lorenzo, M. Ruperez, and J. Egido ACE inhibitors and AT1 receptor antagonists--beyond the haemodynamic effect Nephrol. Dial. Transplant., May 1, 2000; 15(5): 561 - 565. [Full Text] [PDF] |
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C. M. Bamberger, T. Else, A.-M. Bamberger, F. Ulrich Beil, and H. M. Schulte Dissociative Glucocorticoid Activity of Medroxyprogesterone Acetate in Normal Human Lymphocytes J. Clin. Endocrinol. Metab., November 1, 1999; 84(11): 4055 - 4061. [Abstract] [Full Text] |
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R. E. Gilbert, L. L. Wu, D. J. Kelly, A. Cox, J. L. Wilkinson-Berka, C. I. Johnston, and M. E. Cooper Pathological Expression of Renin and Angiotensin II in the Renal Tubule after Subtotal Nephrectomy : Implications for the Pathogenesis of Tubulointerstitial Fibrosis Am. J. Pathol., August 1, 1999; 155(2): 429 - 440. [Abstract] [Full Text] [PDF] |
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Y. Han, M. S. Runge, and A. R. Brasier Angiotensin II Induces Interleukin-6 Transcription in Vascular Smooth Muscle Cells Through Pleiotropic Activation of Nuclear Factor-{kappa}B Transcription Factors Circ. Res., April 2, 1999; 84(6): 695 - 703. [Abstract] [Full Text] [PDF] |
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A.-P. Gimenez-Roqueplo, J. Celerier, G. Schmid, P. Corvol, and X. Jeunemaitre Role of Cysteine Residues in Human Angiotensinogen. CYS232 IS REQUIRED FOR ANGIOTENSINOGEN-PRO MAJOR BASIC PROTEIN COMPLEX FORMATION J. Biol. Chem., December 18, 1998; 273(51): 34480 - 34487. [Abstract] [Full Text] [PDF] |
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K. Tamura, S. Umemura, N. Nyui, K. Hibi, T. Ishigami, M. Kihara, Y. Toya, and M. Ishii Activation of angiotensinogen gene in cardiac myocytes by angiotensin II and mechanical stretch Am J Physiol Regulatory Integrative Comp Physiol, July 1, 1998; 275(1): R1 - R9. [Abstract] [Full Text] [PDF] |
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G. Yang and C. D. Sigmund Regulatory Elements Required for Human Angiotensinogen Expression in HepG2 Cells Are Dispensable in Transgenic Mice Hypertension, March 1, 1998; 31(3): 734 - 740. [Abstract] [Full Text] [PDF] |
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E. Sterneck, L. Tessarollo, and P. F. Johnson An essential role for C/EBPbeta in female reproduction Genes & Dev., September 1, 1997; 11(17): 2153 - 2162. [Abstract] [Full Text] [PDF] |
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