Control of b myosin heavy chain expression in systemic hypertension
and caloric restriction in the rat heart.
Swoap, Steven J., Fadia Haddad, Paul Bodell, and Kenneth M. Baldwin.
Department of Physiology and Biophysics, University of California,
Irvine, Irvine, CA 92717
APStracts 2:0166C, 1995.
In the rat left ventricle (LV), both pressure overload induced by
abdominal aortic constriction (Abcon) and caloric restriction (CR)
induce an increase in the steady state level of the [beta] myosin
heavy chain (MHC) protein and mRNA. Both models also induce a
concomitant decrease in the [alpha] MHC protein and mRNA. The goals
of this study were : 1) to determine if the changes in MHC expression
in the models are due to altered transcription; and 2) to identify
the relative levels of some key factors interacting with the
regulatory regions of these genes. Female Sprague-Dawley rats were
randomly assigned to the following groups 1) normal control (NC); 2)
Abcon; and 3) CR. After 5 weeks of experimental manipulations,
myocardial nuclei were isolated. These nuclei were used for 1)
nuclear run-on assays, or 2) nuclear extract (NE) was prepared and
used for gel mobility shift assays (GMSA). Nuclear run-on assays
demonstrated that the increase in [beta] MHC mRNA and protein
expression in both Abcon and CR can be at least partially attributed
to increased transcription. The concomitant decrease in [alpha] MHC
content can similarly be attributed to a decrease in transcription of
this gene. Furthermore, GMSAs demonstrate that NE from each group
interact differently with certain elements known to be important for
expression in vitro. CR NE have a 25.6 + 7.2% decrease (P <0.05 vs.
NC) in interaction with a thyroid responsive element, a potential
repressor of [beta] MHC transcription. Abcon NE interaction with this
element is not altered from NC. Additionally, Abcon NE has a 50.8 +
20.6% (P <0.05 vs. NC) increase in interaction with the [beta]e2
element, a potential activator of [beta] MHC transcription, while the
CR NE interaction with this element is not altered from NC.
Therefore, these data suggest that while the common adaptive response
to both Abcon and CR is to increase [beta] MHC transcription, the
potential mechanisms employed appear to be inherently different.
Received 29 August 1994; accepted in final form 7 April 1995.
APS Manuscript Number C525-4.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 25 April 1995.