Decreased RhoA expression in myocardium of diabetic rats.
Diabetic cardiomyopathy is 1 of the major causes of death in diabetic patients, but the pathogenesis is unclear. There is evidence that RhoA, a small GTPase, might be involved in cardiac function. This study, therefore, analyzed RhoA expression and activation in hearts of diabetic rats. Male Sprague-Dawley rats were divided into control and diabetic groups of 18 each. Diabetes was induced by intravenous injection of streptozotocin (55 mg/kg). Rats were studied 3 weeks after induction of diabetes. Heart rate, which was measured 24 h/day, decreased by 93 +/- 7 beats/min in diabetic rats. There was a 62% decrease (p < 0.01) in RhoA mRNA expression in heart tissues (left ventricle) of diabetic rats (38.5 +/- 6.7 x 106 molecules/microg total RNA) compared with controls (101 +/- 10.3 x 106 molecules/microg total RNA). Western blot showed a 33% decrease in total RhoA protein expression in heart tissues of diabetic rats compared with controls (p < 0.05). A reduced RhoA translocation in heart tissues of diabetic rats was determined by a 64% decrease in membrane-bound RhoA (p < 0.01 vs. control group), indicating that the activation of RhoA is markedly reduced in diabetic myocardium. Our data suggest that down-regulated RhoA may be involved in cardiomyopathy in diabetic rats.
Tang
Jiping
J
Department of Physiology, University of Mississippi Medical Center, Jackson, MS 39216, USA. jipingtang@yahoo.com
Fitzgerald
Sharyn M
SM
Boughtman
Brandi N
BN
Cole
Samuel W
SW
Brands
Michael W
MW
Zhang
John H
JH
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism*; D015536:Down-Regulation; D005786:Gene Expression Regulation; D006321:Heart / Q000033:anatomy & histology; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin / Q000494:pharmacology; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D013311:Streptozocin; D020742:rhoA GTP-Binding Protein