Differential changes in phospholipase D and phosphatidate phosphohydrolase activities in ischemia–reperfusion of rat heart

• Published in: Archives of biochemistry and biophysics Vol. 436; no. 1; pp. 136 - 144
• Main Authors: Asemu, Girma, Dent, Melissa R., Singal, Tushi, Dhalla, Naranjan S., Tappia, Paramjit S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2005
• Subjects: Animals; Cardiac ischemia–reperfusion; Diacylglycerol; Diglycerides - metabolism; Disease Models, Animal; Heart Ventricles - drug effects; Myocardial Ischemia - drug therapy; Myocardial Ischemia - enzymology; Phosphatidate Phosphatase - metabolism; Phosphatidate Phosphatase - pharmacology; Phosphatidate phosphohydrolase; Phosphatidic acid; Phosphatidic Acids - metabolism; Phospholipase D; Phospholipase D - metabolism; Phospholipase D - pharmacology; Rats; Reperfusion Injury - drug therapy; Reperfusion Injury - enzymology; Sarcolemma; Sarcolemma - drug effects; Sarcolemma - metabolism; Sarcoplasmic reticulum; Sarcoplasmic Reticulum - drug effects; Sarcoplasmic Reticulum - metabolism; Time Factors; Ventricular Function; Sarcolemma; Sarcoplasmic reticulum; Phosphatidate phosphohydrolase; Diacylglycerol; Cardiac ischemia–reperfusion; Phospholipase D; Phosphatidic acid
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/j.abb.2005.02.002

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.