(Hypertension. 1995;25:415-420.)
© 1995 American Heart Association, Inc.
Articles |
Regulation of Endothelial Constitutive Nitric Oxide Synthase by Protein Kinase C
From the Division of Cardiology, Emory University School of Medicine, and the Atlanta Veterans Administration Medical Center, Atlanta, Georgia.
Correspondence to David G. Harrison, MD, Division of Cardiology, Emory University School of Medicine, PO Drawer LL, Atlanta, GA 30322.
Abstract Protein kinase C (PKC) plays a key role in a variety of signal transduction processes. The promoter region of the endothelial constitutive nitric oxide synthase (ecNOS) gene contains a transcriptional factor AP-1 binding element. In the present study, we sought to determine the effect of PKC inhibition on the expression of ecNOS in cultured bovine aortic endothelial cells (BAEC). The PKC inhibitor staurosporine (10 to 100 nmol/L) increased the expression of ecNOS mRNA, assessed by Northern analysis, in a dose-dependent manner. A newly developed, more specific PKC inhibitor, chelerythrine (1 to 3 µmol/L), also increased the level of ecNOS mRNA. Incubation of BAEC with phorbol 12-myristate 13-acetate (100 nmol/L) for 24 hours, which downregulates PKC, increased ecNOS mRNA expression. The protein content of ecNOS, assessed by Western analysis, was also increased in staurosporine-treated or chelerythrine-treated BAEC. The release of nitrogen oxides from staurosporine-treated or chelerythrine-treated cells both under basal conditions and in response to calcium ionophore A23187 was significantly increased (P<.05). In conclusion, the present study suggests that regulation of ecNOS is mediated by PKC. The increased release of nitric oxide induced by PKC inhibition may play a protective role against atherogenic process.
Key Words: endothelium • nitric oxide • phorbol esters • protein kinase C
This article has been cited by other articles:
 |
|
 |
|
  N. Sud, S. Wedgwood, and S. M. Black Protein kinase C{delta} regulates endothelial nitric oxide synthase expression via Akt activation and nitric oxide generation Am J Physiol Lung Cell Mol Physiol, March 1, 2008; 294(3): L582 - L591. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Miyazaki-Akita, T. Hayashi, Q. F. Ding, H. Shiraishi, T. Nomura, Y. Hattori, and A. Iguchi 17beta-Estradiol Antagonizes the Down-Regulation of Endothelial Nitric-Oxide Synthase and GTP Cyclohydrolase I by High Glucose: Relevance to Postmenopausal Diabetic Cardiovascular Disease J. Pharmacol. Exp. Ther., February 1, 2007; 320(2): 591 - 598. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Rask-Madsen and G. L. King Proatherosclerotic Mechanisms Involving Protein Kinase C in Diabetes and Insulin Resistance Arterioscler Thromb Vasc Biol, March 1, 2005; 25(3): 487 - 496. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Aramoto, J. W. Breslin, P. J. Pappas, R. W. Hobson II, and W. N. Duran Vascular endothelial growth factor stimulates differential signaling pathways in in vivo microcirculation Am J Physiol Heart Circ Physiol, October 1, 2004; 287(4): H1590 - H1598. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Olson, R. Oeckler, X. Li, L. Du, F. Traganos, X. Zhao, and T. Burke-Wolin Angiotensin II stimulates nitric oxide production in pulmonary artery endothelium via the type 2 receptor Am J Physiol Lung Cell Mol Physiol, September 1, 2004; 287(3): L559 - L568. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Tickerhoof, P A. Farrell, and D. H. Korzick Alterations in rat coronary vasoreactivity and vascular protein kinase C isoforms in Type 1 diabetes Am J Physiol Heart Circ Physiol, December 1, 2003; 285(6): H2694 - H2703. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. K. Trauernicht, H. Sun, K. P. Patel, and W. G. Mayhan Enalapril Prevents Impaired Nitric Oxide Synthase-Dependent Dilatation of Cerebral Arterioles in Diabetic Rats Stroke, November 1, 2003; 34(11): 2698 - 2703. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-C. Schneider, D. El Kebir, C. Chereau, S. Lanone, X.-L. Huang, A. S. De Buys Roessingh, J.-C. Mercier, J. Dall'Ava-Santucci, and A. T. Dinh-Xuan Involvement of Ca2+/calmodulin-dependent protein kinase II in endothelial NO production and endothelium-dependent relaxation Am J Physiol Heart Circ Physiol, June 1, 2003; 284(6): H2311 - H2319. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-C. Schneider, D. El Kebir, C. Chereau, J.-C. Mercier, J. Dall'Ava-Santucci, and A. T. Dinh-Xuan Involvement of Na+/Ca2+ exchanger in endothelial NO production and endothelium-dependent relaxation Am J Physiol Heart Circ Physiol, August 1, 2002; 283(2): H837 - H844. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. G. Bohlen and G. P. Nase Obesity lowers hyperglycemic threshold for impaired in vivo endothelial nitric oxide function Am J Physiol Heart Circ Physiol, July 1, 2002; 283(1): H391 - H397. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Spyridopoulos, C. Luedemann, D. Chen, M. Kearney, D. Chen, T. Murohara, N. Principe, J. M. Isner, and D. W. Losordo Divergence of Angiogenic and Vascular Permeability Signaling by VEGF: Inhibition of Protein Kinase C Suppresses VEGF-Induced Angiogenesis, but Promotes VEGF-Induced, NO-Dependent Vascular Permeability Arterioscler Thromb Vasc Biol, June 1, 2002; 22(6): 901 - 906. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Freedman, C. Parker III, L. Li, J. A. Perlman, B. Frei, V. Ivanov, L. R. Deak, M. D. Iafrati, and J. D. Folts Select Flavonoids and Whole Juice From Purple Grapes Inhibit Platelet Function and Enhance Nitric Oxide Release Circulation, June 12, 2001; 103(23): 2792 - 2798. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Bove, P. Neumann, N. Gertzberg, and A. Johnson Role of ecNOS-derived NO in mediating TNF-induced endothelial barrier dysfunction Am J Physiol Lung Cell Mol Physiol, May 1, 2001; 280(5): L914 - L922. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Beckman, A. B. Goldfine, M. B. Gordon, and M. A. Creager Ascorbate Restores Endothelium-Dependent Vasodilation Impaired by Acute Hyperglycemia in Humans Circulation, March 27, 2001; 103(12): 1618 - 1623. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Govers and T. J. Rabelink Cellular regulation of endothelial nitric oxide synthase Am J Physiol Renal Physiol, February 1, 2001; 280(2): F193 - F206. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Meier and G. L King Protein kinase C activation and its pharmacological inhibition in vascular disease Vascular Medicine, August 1, 2000; 5(3): 173 - 185. [Abstract] [PDF]
|
|
|
|
 |
|
 R. A. P. Skyrme-Jones, R. C. O'Brien, K. L. Berry, and I. T. Meredith Vitamin E supplementation improves endothelial function in type I diabetes mellitus: a randomized, placebo-controlled study J. Am. Coll. Cardiol., July 1, 2000; 36(1): 94 - 102. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B.-W. Hochleitner, E.-O. Hochleitner, P. Obrist, T. Eberl, A. Amberger, Q. Xu, R. Margreiter, and G. Wick Fluid Shear Stress Induces Heat Shock Protein 60 Expression in Endothelial Cells In Vitro and In Vivo Arterioscler Thromb Vasc Biol, March 1, 2000; 20(3): 617 - 623. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Li and U. Förstermann Structure-Activity Relationship of Staurosporine Analogs in Regulating Expression of Endothelial Nitric-Oxide Synthase Gene Mol. Pharmacol., March 1, 2000; 57(3): 427 - 435. [Abstract] [Full Text]
|
|
|
|
|
|
K. Kuboki, Z. Y. Jiang, N. Takahara, S. W. Ha, M. Igarashi, T. Yamauchi, E. P. Feener, T. P. Herbert, C. J. Rhodes, and G. L. King Regulation of Endothelial Constitutive Nitric Oxide Synthase Gene Expression in Endothelial Cells and In Vivo : A Specific Vascular Action of Insulin Circulation, February 15, 2000; 101(6): 676 - 681. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. D Rakhit, R. J Edwards, and M. S Marber Nitric oxide, nitrates and ischaemic preconditioning Cardiovasc Res, August 15, 1999; 43(3): 621 - 627. [Full Text] [PDF]
|
|
|
|
 |
|
 J. F. KEANEY JR., D. I. SIMON, and J. E. FREEDMAN Vitamin E and vascular homeostasis: implications for atherosclerosis FASEB J, June 1, 1999; 13(9): 965 - 975. [Abstract] [Full Text]
|
|
|
|
|
|
H. Ando, T. Kubin, W. Schaper, and J. Schaper Cardiac microvascular endothelial cells express alpha -smooth muscle actin and show low NOS III activity Am J Physiol Heart Circ Physiol, May 1, 1999; 276(5): H1755 - H1768. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Bouloumie, V. B. Schini-Kerth, and R. Busse Vascular endothelial growth factor up-regulates nitric oxide synthase expression in endothelial cells Cardiovasc Res, March 1, 1999; 41(3): 773 - 780. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Su, W. Han, C. Giraldo, Y. De Li, and E. R. Block Effect of Cigarette Smoke Extract on Nitric Oxide Synthase in Pulmonary Artery Endothelial Cells Am. J. Respir. Cell Mol. Biol., November 1, 1998; 19(5): 819 - 825. [Abstract] [Full Text]
|
|
|
|
|
|
U. Förstermann, J.-p. Boissel, and H. Kleinert Expressional control of the `constitutive' isoforms of nitric oxide synthase (NOS I and NOS III) FASEB J, July 1, 1998; 12(10): 773 - 790. [Abstract] [Full Text]
|
|
|
|
 |
|
 A. F. Castro, C. Amorena, A. Muller, G. Ottaviano, M. T. Tellez-Inon, and A. C. Taquini Extracellular ATP and bradykinin increase cGMP in vascular endothelial cells via activation of PKC Am J Physiol Cell Physiol, July 1, 1998; 275(1): C113 - C119. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. E. Sieber, R. J. Traystman, P. R. Brown, L. J. Martin, and F. M. Faraci Protein Kinase C Expression and Activity After Global Incomplete Cerebral Ischemia in Dogs • Editorial Comment Stroke, July 1, 1998; 29(7): 1445 - 1453. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. B. Williams, A. B. Goldfine, F. K. Timimi, H. H. Ting, M.-A. Roddy, D. C. Simonson, and M. A. Creager Acute Hyperglycemia Attenuates Endothelium-Dependent Vasodilation in Humans In Vivo Circulation, May 5, 1998; 97(17): 1695 - 1701. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Li, S. A. Oehrlein, T. Wallerath, I. Ihrig-Biedert, P. Wohlfart, T. Ulshöfer, T. Jessen, T. Herget, U. Förstermann, and H. Kleinert Activation of Protein Kinase Calpha and/or epsilon Enhances Transcription of the Human Endothelial Nitric Oxide Synthase Gene Mol. Pharmacol., April 1, 1998; 53(4): 630 - 637. [Abstract] [Full Text]
|
|
|
|
 |
|
 L. J. Andries, D. L. Brutsaert, and S. U. Sys Nonuniformity of Endothelial Constitutive Nitric Oxide Synthase Distribution in Cardiac Endothelium Circ. Res., February 9, 1998; 82(2): 195 - 203. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Hishikawa, B. S. Oemar, Z. Yang, and T. F. Luscher Pulsatile Stretch Stimulates Superoxide Production and Activates Nuclear Factor-{kappa}B in Human Coronary Smooth Muscle Circ. Res., November 19, 1997; 81(5): 797 - 803. [Abstract] [Full Text]
|
|
|
|
|
|
Q. Huang and Y. Yuan Interaction of PKC and NOS in signal transduction of microvascular hyperpermeability Am J Physiol Heart Circ Physiol, November 1, 1997; 273(5): H2442 - H2451. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Zuo and R. A. Johns Inhalational Anesthetics Up-Regulate Constitutive and Lipopolysaccharide-Induced Inducible Nitric Oxide Synthase Expression and Activity Mol. Pharmacol., October 1, 1997; 52(4): 606 - 612. [Abstract] [Full Text]
|
|
|
|
 |
|
 G. Garcia-Cardena, R. Fan, D. F. Stern, J. Liu, and W. C. Sessa Endothelial Nitric Oxide Synthase Is Regulated by Tyrosine Phosphorylation and Interacts with Caveolin-1 J. Biol. Chem., November 1, 1996; 271(44): 27237 - 27240. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Beckman, A. B. Goldfine, M. B. Gordon, L. A. Garrett, and M. A. Creager Inhibition of Protein Kinase C{beta} Prevents Impaired Endothelium-Dependent Vasodilation Caused by Hyperglycemia in Humans Circ. Res., January 11, 2002; 90(1): 107 - 111. [Abstract] [Full Text] [PDF]
|
|