Defective sarcolemmal phospholipase C signaling in diabetic cardiomyopathy.
Phospholipase C (PLC) activity is known to influence cardiac function. This study was undertaken to examine the status of PLC beta3 in the cardiac cell plasma membrane (sarcolemma, SL) in an experimental model of chronic diabetes. SL membrane was isolated from diabetic rat hearts at 8 weeks after a single i.v. injection of streptozotocin (65 mg/kg body weight). The total SL PLC was decreased in diabetes and was associated with a decrease in SL PLC beta3 activity, which immunofluorescence in frozen diabetic left ventricular tissue sections revealed to be due to a decrease in PLC beta3 protein abundance. In contrast, the SL abundance of Gqalpha was significantly increased during diabetes. These changes were associated with a loss of contractile function (+/- dP/dt). A 2-week insulin treatment of 6-week diabetic animals partially normalized all of these parameters. These findings suggest a defect in PLC beta3-mediated signaling processes may contribute to the cardiac dysfunction seen during diabetes.
Tappia
Paramjit S
PS
Institute of Cardiovascular Sciences, St. Boniface Hospital Research Centre, Manitoba, Canada. ptappia@sbrc.ca
Asemu
Girma
G
Aroutiounova
Nina
N
Dhalla
Naranjan S
NS
D000818:Animals; D009202:Cardiomyopathies / Q000201:enzymology* / Q000209:etiology; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology; D003925:Diabetic Angiopathies / Q000201:enzymology*; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000032:analysis / Q000378:metabolism; D006352:Heart Ventricles / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D015544:Inositol 1,4,5-Trisphosphate / Q000032:analysis / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D007527:Isoenzymes / Q000032:analysis / Q000378:metabolism*; D008297:Male; D032383:Myocytes, Cardiac / Q000276:immunology; D054799:Phospholipase C beta; D051381:Rats; D012508:Sarcolemma / Q000201:enzymology* / Q000276:immunology; D010738:Type C Phospholipases / Q000032:analysis / Q000378:metabolism*
D007328:Insulin; D007527:Isoenzymes; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases; D054799:Phospholipase C beta; C518041:Plcb3 protein, rat; D043802:GTP-Binding Protein alpha Subunits, Gq-G11