Differential gene transcriptional regulation of Gi isoforms and Gs protein expression in diabetic rat hearts.
Many cardiac diseases can be associated with alterations in the function and quantity of G proteins. We examined the gene expressions and protein levels of Gi-1alpha, Gi-2alpha, Gi-3alpha and G(s alpha) in ventricular myocardial preparations from rats 4-6 weeks after induction of diabetes with streptozotocin in comparison with those from age-matched control rats. Diabetic rat myocardium exhibited reductions in the protein levels of Gi-2alpha and Gi-3alpha by 22+/-2% and 57+/-2%, respectively. In diabetes, 22% and 53% reductions in myocardial mRNA levels of Gi-2alpha and Gi-3alpha were observed. Although a faint protein signal of Gi-1alpha was detectable, no apparent expression of mRNA for Gi-1alpha was found in either control or diabetic myocardium. The reduced protein and mRNA levels of Gi-2alpha and Gi-3alpha were prevented by insulin therapy. No change was found in the protein and mRNA levels of G(s alpha) in diabetic myocardium. In conclusion, diabetes leads to a differential regulation of protein expressions of G(i alpha) isoforms and G(s alpha) in ventricular myocardium. The reduced expression of Gi-2alpha and Gi-3alpha proteins can be explained, at least in part, by the decreases in the transcriptional levels.
Matsuda
N
N
Department of Anesthesiology and Intensive Care, Hokkaido University School of Medicine, Sapporo, Japan.
Hattori
Y
Y
Gando
S
S
Watanuki
S
S
Kemmotsu
O
O
Kanno
M
M
D000818:Animals; D015152:Blotting, Northern; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000096:biosynthesis / Q000235:genetics*; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000096:biosynthesis / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics*; D006352:Heart Ventricles / Q000378:metabolism; D007536:Isomerism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D017208:Rats, Wistar
D012333:RNA, Messenger; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D019205:GTP-Binding Protein alpha Subunits, Gs