(Hypertension. 1999;33:1348-1352.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
p53-Mediated Upregulation of BAX Gene Transcription Is Not Involved in Bax-
Protein Overexpression in the Left Ventricle of Spontaneously Hypertensive Rats
From the Vascular Pathophysiology Unit, School of Medicine, University of Navarra, Pamplona (M.A.F., G.Z., S.R., E.D., F.J.B., A.F., J.D.), and Department of Medicine, School of Medicine, University of Zaragoza, Zaragoza (J.D.), Spain.
Correspondence and reprint requests to Dr Javier Díez, Unidad de Fisiopatología Vascular, Facultad de Medicina, C/Irunlarrea s/n, 31080 Pamplona, Spain.
Abstract—An association of
increased apoptosis with overexpression of the
proapoptotic protein Bax-
has been reported in the left
ventricle of adult spontaneously hypertensive rats (SHR). Both
alterations were corrected in SHR that received long-term treatment
with the AT1 antagonist losartan. To
gain insight into the regulation of cardiac Bax- protein in genetic
hypertension, we investigated the expression of the protein p53 (a
BAX gene transcription factor) and BAX mRNA in the left
ventricle of 30-week-old Wistar-Kyoto rats (WKY), SHR, and SHR treated
with losartan (20 mg · kg-1 ·
d-1) during 14 weeks before death. The expression of p53
and Bax proteins was assessed by Western blot analysis. The
expression of BAX mRNA was assessed by Northern blot analysis.
The density of apoptotic cells was assessed by direct
immunoperoxidase detection of biotin-labeled deoxyuridine
nucleotides. Compared with WKY, untreated SHR exhibited
increased apoptosis (P<0.05), increased Bax-
protein (P<0.05), and similar levels of p53 protein and
BAX mRNA. Losartan given long term was associated with the
normalization of apoptosis and Bax- protein expression. The
expression of BAX mRNA was decreased (P<0.05) in
treated SHR compared with untreated SHR. No changes in the expression
of p53 protein were observed in losartan-treated SHR. These
results suggest that overexpression of the Bax- protein seen in the
left ventricle of adult SHR with increased apoptosis is not
related to a p53-mediated upregulation of BAX gene
transcription. Our data also suggest that normalization of Bax-
protein observed in SHR after long-term blockade of
angiotensin II type 1 receptors may be due to the
inhibition of BAX gene transcription.
Key Words: apoptosis • BAX gene • protein, Bax- • ventricular function, left • p53 • rats, inbred SHR
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