Differential changes in phospholipase D and phosphatidate phosphohydrolase activities in ischemia-reperfusion of rat heart.
Phospholipase D (PLD2) produces phosphatidic acid (PA), which is converted to 1,2 diacylglycerol (DAG) by phosphatidate phosphohydrolase (PAP2). Since PA and DAG regulate Ca(2+) movements, we examined PLD2 and PAP2 in the sarcolemma (SL) and sarcoplasmic reticular (SR) membranes from hearts subjected to ischemia and reperfusion (I-R). Although SL and SR PLD2 activities were unaltered after 30 min ischemia, 5 min reperfusion resulted in a 36% increase in SL PLD2 activity, whereas 30 min reperfusion resulted in a 30% decrease in SL PLD2 activity, as compared to the control value. SR PLD2 activity was decreased (39%) after 5 min reperfusion, but returned to control levels after 30 min reperfusion. Ischemia for 60 min resulted in depressed SL and SR PLD2 activities, characterized with reduced V(max) and increased K(m) values, which were not reversed during reperfusion. Although the SL PAP2 activity was decreased (31%) during ischemia and at 30 min reperfusion (28%), the SR PAP2 activity was unchanged after 30 min ischemia, but was decreased after 5 min reperfusion (25%) and almost completely recovered after 30 min reperfusion. A 60 min period of ischemia followed by reperfusion caused an irreversible depression of SL and SR PAP2 activities. Our results indicate that I-R induced cardiac dysfunction is associated with subcellular changes in PLD2 and PAP2 activities.
Asemu
Girma
G
Institute of Cardiovascular Sciences, St. Boniface Hospital Research Centre, Department of Human Nutritional Sciences, Faculty of Human Ecology, University of Manitoba, Winnipeg, Canada R2H 2A6.
Dent
Melissa R
MR
Singal
Tushi
T
Dhalla
Naranjan S
NS
Tappia
Paramjit S
PS
D000818:Animals; D004075:Diglycerides / Q000378:metabolism; D004195:Disease Models, Animal; D006352:Heart Ventricles / Q000187:drug effects; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000201:enzymology*; D010711:Phosphatidate Phosphatase / Q000378:metabolism* / Q000494:pharmacology; D010712:Phosphatidic Acids / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D015427:Reperfusion Injury / Q000188:drug therapy / Q000201:enzymology*; D012508:Sarcolemma / Q000187:drug effects / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D016276:Ventricular Function
C011439:1,2-diacylglycerol; D004075:Diglycerides; D010712:Phosphatidic Acids; D010711:Phosphatidate Phosphatase; D010739:Phospholipase D