CONTROL OF BETA-MYOSIN HEAVY-CHAIN EXPRESSION IN SYSTEMIC HYPERTENSION AND CALORIC RESTRICTION IN THE RAT-HEART

In the rat left ventricle, both pressure overload induced by abdominal aortic constriction (Abcon) and caloric restriction (CR) induce an in crease in the steady-state level of the beta-myosin heavy chain (MHC) protein and mRNA. Both models also induce a concomitant decrease in th e alpha-MHC protein arid mRNA. The goals of this study were to 1) dete rmine if the changes in MHC expression in the models are due to altere d transcription and 2) identify the relative levels of some key factor s interacting with the regulatory regions of these genes. Female Sprag ue-Dawley rats were randomly assigned to the following groups: 1) norm al control (NC), 2) Abcon, and 3) CR. After 5 wk of experimental manip ulations, myocardial nuclei were isolated. These nuclei were used for 1) nuclear run-on assays or 2) nuclear extract, which was prepared and used for gel mobility shift assays (GMSAs). Nuclear run-on assays dem onstrated that the increase in beta-MHC mRNA and protein expression in both Abcon and CR can be at least partially attributed to increased t ranscription. The concomitant decrease in alpha-MHC content can simila rly be attributed to a decrease in transcription of this gene. Further more, GMSAs demonstrate that nuclear extract from each group interact differently with certain elements known to be important for expression in vitro. CR nuclear extracts 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 nuclear extract interactio n with this element is not altered from NC. In addition, Abcon nuclear extract has a 50.8 +/- 20.6% (P < 0.05 vs. NC) increase in interactio n with the beta e(2) element, a potential activator of beta-MHC transc ription, whereas the CR nuclear extract interaction with this element is not altered from NC. Therefore, these data suggest that, whereas th e common adaptive response to both Abcon and CR is to increase beta-MH C transcription, the potential mechanisms employed appear to be inhere ntly different.