Differential expression of Gs in a murine model of homocysteinemic heart failure.
High plasma homocysteine levels are a known risk factor in heart failure and sudden cardiac death. The G proteins, G(s) (stimulatory) and G(i) (inhibitory), are involved in calcium regulation; overexpression has pathological consequences. The aims of this study were to examine the differential expression of G(s) G protein and G(i) 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-beta-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 G(s) G protein was downregulated in cardiac tissue of heterozygous CBS KO mice to 46% that of control hearts. However, the intracellular G(i) 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 G(s) and G(i) 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.
Department of Physiology and Biophysics, University of Louisville School of Medicine, Louisville, Kentucky 40202, USA.
Thomas P
TP
Vacek
Utpal
U
Sen
Neetu
N
Tyagi
Jonathan C
JC
Vacek
Munish
M
Kumar
William M
WM
Hughes
John C
JC
Passmore
Suresh C
SC
Tyagi
D000818:Animals; D020013:Calcium Signaling; D002461:Cell Line, Transformed; D003541:Cystathionine beta-Synthase / Q000172:deficiency / Q000235:genetics; D004195:Disease Models, Animal; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism*; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism*; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism*; D020138:Hyperhomocysteinemia / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism*
D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D019205:GTP-Binding Protein alpha Subunits, Gs; D003541:Cystathionine beta-Synthase