Subcellular alterations in cardiac phospholipase D activity in chronic diabetes.
Several studies have suggested that myocardial phospholipase D (PLD) and its hydrolytic product, phosphatidic acid (PtdOH), may regulate Ca2+ movements and contractile performance of the heart. Since abnormal intracellular Ca2+ handling is a major factor of myocardial dysfunction in chronic diabetes, we examined subcellular changes in PLD activity in myocardium from insulin-dependent diabetic rats. Diabetes in rats was induced by a single i.v. injection of streptozotocin (65 mg/kg body wt) and 8 weeks later the ventricular tissue was processed for the isolation of sarcolemma, sarcoplasmic reticulum and mitochondria. Compared to age-matched controls, the sarcolemmal, sarcoplasmic reticular and mitochondrial PLD activities were significantly depressed in the diabetic animals. The depressed sarcolemmal PLD activity was normalized, whereas the sarcoplasmic reticular and mitochondrial enzyme activities were partially reversed upon treating the 6-week diabetic rats with insulin for a period of 2 weeks. These data suggest that the reduction of PLD-derived PtdOH may lead to an impairment in this phospholipid signal transduction pathway and subsequent cardiac dysfunction in chronic diabetes.
Williams
S A
SA
St. Boniface General Hospital Research Centre, Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Tappia
P S
PS
Yu
C H
CH
Binaglia
L
L
Panagia
V
V
Dhalla
N S
NS
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology* / Q000473:pathology; D007425:Intracellular Membranes / Q000201:enzymology; D008297:Male; D008929:Mitochondria, Heart / Q000201:enzymology / Q000648:ultrastructure; D009206:Myocardium / Q000201:enzymology* / Q000648:ultrastructure*; D010739:Phospholipase D / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012508:Sarcolemma / Q000201:enzymology; D012519:Sarcoplasmic Reticulum / Q000201:enzymology; D013347:Subcellular Fractions / Q000201:enzymology*
D010739:Phospholipase D