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Differential expression of Gs and Gi in mice with homocysteinemic heart failure
Author(s) -
Vacek Thomas Paul,
Moshal Karni Singh,
Sen Utpal,
Tyagi Neetu,
Steed Mesia,
Kumar Munish,
Passmore John,
Tyagi Suresh
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1155.19
Subject(s) - medicine , endocrinology , paracrine signalling , receptor , homocysteine , in vivo , intracellular , agonist , heart failure , biology , g protein , chemistry , microbiology and biotechnology
High plasma homocysteine levels are a known risk factor in heart failure and sudden cardiac death. β1‐adrenergic receptor, a G protein coupled receptor (GPCR) containing only Gα s G protein subunit, undergoes down‐regulation in heart failure. The aims of this study were to examine the differential expression of Gα s G protein and Gα i (inhibitory) in the hearts of hyperhomocysteinemic (Hhcy) mice, and to determine if homocysteine acts via a paracrine mechanism in vivo or in isolation as an agonist in cell culture to mediate the change in G protein isoforms. To create Hhcy, mice were treated with Hcy (0.67mg/mL) in water for 12 weeks. Echocardiogram and EKG were performed on each mouse. Mice were sacrificed, hearts were excised, cardiac tissue homogenates were prepared, and western blots were performed to determine content of Gα s and Gαi. The results suggest that Gα s G protein was down regulated in cardiac tissue of Hcy mice to 54% that of control hearts. However, the intracellular Gα i G protein content remained the same in Hhcy mice. Mouse aortic endothelial cells (MAECs) and transformed cardiomyocyte HL‐1 cells were treated with varying concentrations of homocysteine for 24 hours. The results suggest no detectable differential Gα s and Gα i expression. This suggests that homocysteine acts via paracrine mechanism in vivo, mediating changes in intracellular Gα s G protein content related to cardiac dysfunction in Hhcy.