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Differential expression of Gs in a murine model of homocysteinemic heart failure

Authors Vacek T, Sen U, Tyagi N, Vacek J, Kumar M, Hughes W, Passmore J, Tyagi S

Published 4 December 2008 Volume 2009:5 Pages 79—84

DOI https://doi.org/10.2147/VHRM.S4121

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Peer reviewer comments 4


Thomas P Vacek,  Utpal Sen, Neetu Tyagi, Jonathan C Vacek, Munish Kumar, et al

Department of Physiology and Biophysics, University of Louisville School of Medicine, Louisville, Kentucky – 40202, USA

Abstract: High plasma homocysteine levels are a known risk factor in heart failure and sudden cardiac death. The G proteins, Gs (stimulatory) and Gi (inhibitory), are involved in calcium regulation; overexpression has pathological consequences. The aims of this study were to examine the differential expression of Gs G protein and Gi in the hearts of hyperhomocysteinemic (Hhcy) mice, and to determine if homocysteine (Hcy) acts as an agonist in cell culture to mediate the change in G protein isoforms. To create Hhcy, heterozygous cystathionine-β-synthase (CBS) knockout (KO) mice were used. Mice were sacrificed, hearts were excised, cardiac tissue homogenates were prepared, and Western blots were performed. The results suggested that Gs G protein was downregulated in cardiac tissue of heterozygous CBS KO mice to 46% that of control hearts. However, the intracellular Gi G protein content remained the same in heterozygous CBS KO mice. Transformed cardiomyocyte HL-1 cells were treated with varying concentrations of homocysteine. The results suggested no detectable differential Gs and Gi expression. This suggested that Hcy did not act as an agonist in vitro to alter G protein content, but that Hcy produced some other in vivo effects to incur these results.

Keywords: homocysteine, G proteins, heart failure, GPCR, HL-1

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