title: Decreased cardiac sarcoplasmic reticulum Ca2+ -ATPase activity contributes to cardiac dysfunction in streptozotocin-induced diabetic rats.
abstract: Diabetic cardiomyopathy is characterized by reduced cardiac contractility due to direct changes in myocardium function independent of vascular disease. This study is to investigate the alterations of cardiac sarcoplasmic reticulum Ca2+ -ATPase activity and cardiac function in streptozotocin-induced diabetic rats. Diabetes mellitus (DM) was induced in male Wistar rats by intraperitoneal injection of streptozotocin. The activity of myocardium sarcoplasmic reticulum Ca2+ -ATPase and the left ventricular hemodynamic parameters were measured in DM rats 4 weeks, 6 weeks and 8 weeks after streptozotocin was administered. Phospholamban mRNA expression was detected by reverse transcription-polymerase chain reaction, and the protein levels of phospholamban and sarcoplasmic reticulum Ca2+ -ATPase were determined by Western blot. Normal rats served as control group. It was found that in DM rats 4 weeks after streptozotocin injection, the cardiac function, myocardium sarcoplasmic reticulum Ca2+ -ATPase activity, phospholamban mRNA and phospholamban protein were not significantly changed compared with those in the control rats. At 6 and 8 weeks after the streptozotocin injection, DM rats showed a significant decrease in sarcoplasmic reticulum Ca2+ -ATPase activity and cardiac function, as indicated by an increase of LVEDP and a marked depression in LVSP and +/- dP/dtmax. At the same time points, increases in phospholamban mRNA and protein levels were observed in DM rats. Sarcoplasmic reticulum Ca2+ -ATPase protein level showed no significant alterations in all DM rats compared with that in control rats. Our work confirms that sarcoplasmic reticulum Ca2+ -ATPase activity is depressed in rats with streptozotocin-induced DM, which is accompanied by elevated phospholamban protein level thus contribute to the pathogenesis of cardiac dysfunction in diabetic rats.
authors.affiliation: Institute of Cardiology, The First Affiliated Hospital, China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Zhao
authors.forename: Shen-Jiang
authors.initials: SJ
authors.lastname: Hu
authors.forename: Jiang
authors.initials: J
authors.lastname: Li
authors.forename: Yun
authors.initials: Y
authors.lastname: Mou
authors.forename: Bao-Ping
authors.initials: BP
authors.lastname: Chen
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xia
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D015870:Gene Expression / Q000235:genetics; D006321:Heart / Q000503:physiopathology; D008297:Male; D009206:Myocardium / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018487:Ventricular Dysfunction, Left / Q000378:metabolism* / Q000503:physiopathology; D000099211:Phospholamban
chemical_list: D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D012333:RNA, Messenger; D000099211:Phospholamban