Table of Contents
ISRN Endocrinology
Volume 2012 (2012), Article ID 736860, 12 pages
http://dx.doi.org/10.5402/2012/736860
Research Article

Downregulation in GATA4 and Downstream Structural and Contractile Genes in the db/db Mouse Heart

1Laboratory of Diabetes and Exercise Metabolism, Department of Physiology, Midwestern University, 19555 North 59th Avenue, Glendale, AZ, 85308, USA
2Laboratory of Cardiovascular Biochemistry, Centre Hospitalier de L’Université de Montréal-Hôtel-Dieu, 3850 St-Urbaiw Street, Montreal, QC, Canada H2W 1T8

Received 13 December 2011; Accepted 2 January 2012

Academic Editors: C. Fürnsinn, V. Saengsirisuwan, and Y. Tajiri

Copyright © 2012 Tom L. Broderick et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Reduced expression of GATA4, a transcriptional factor for structural and cardioprotective genes, has been proposed as a factor contributing to the development of cardiomyopathy. We investigated whether the reduction of cardiac GATA4 expression reported in diabetes alters the expression of downstream genes, namely, atrial natriuretic peptide (ANP), B-type natriuretic, peptide (BNP), and α- and β-myosin heavy chain (MHC). db/db mice, a model of type 2 diabetes, with lean littermates serving as controls, were studied. db/db mice exhibited obesity, hyperglycemia, and reduced protein expression of cardiac GLUT4 and IRAP (insulin-regulated aminopeptidase), the structural protein cosecreted with GLUT4. Hearts from db/db mice had reduced protein expression of GATA4 (~35%) with accompanying reductions in mRNA expression of ANP (~40%), BNP (~85%), and α-MHC mRNA (~50%) whereas expression of β-MHC mRNA was increased by ~60%. Low GATA4 was not explained by an increased ligase or atrogin1 expression. CHIP protein content was modestly downregulated (27%) in db/db mice whereas mRNA and protein expression of the CHIP cochaperone HSP70 was significantly decreased in db/db hearts. Our results indicate that low GATA4 in db/db mouse heart is accompanied by reduced expression of GATA4-regulated cardioprotective and structural genes, which may explain the development of cardiomyopathy in diabetes.