Modification of heart sarcolemmal phosphoinositide pathway by lysophosphatidylcholine

• Published in: Biochimica et biophysica acta Vol. 1349; no. 3; pp. 264 - 274
• Main Authors: Liu, Song-Yan, Yu, Chang-Hua, Hays, Jean-Anne, Panagia, Vincenzo, Dhalla, Naranjan S
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 30.11.1997
• Subjects: 1-Phosphatidylinositol 4-Kinase - antagonists & inhibitors; Adenosine Triphosphate - pharmacology; Animals; Calcium - pharmacology; Cardiac sarcolemma; Diabetes; Diabetes Mellitus, Experimental - metabolism; diet-related diseases; Heart - drug effects; human nutrition; Ischemia-reperfusion; Lysophosphatidylcholine; Lysophosphatidylcholines - chemistry; Lysophosphatidylcholines - pharmacology; Male; membranes; myocardial membrane; Myocardial Reperfusion Injury - metabolism; Myocardium - enzymology; Phosphatidylinositol 4,5-Diphosphate - metabolism; Phosphatidylinositol kinase; Phosphatidylinositols - metabolism; Phosphoinositide-phospholipase C; Phosphotransferases (Alcohol Group Acceptor) - antagonists & inhibitors; Plasmalogens - pharmacology; Rats; Rats, Sprague-Dawley; Sarcolemma - drug effects; Sarcolemma - enzymology; Sarcolemma - metabolism; Signal Transduction - drug effects; Signal Transduction - physiology; Structure-Activity Relationship; Type C Phospholipases - metabolism; lyso-PtdEth: lysophosphatidylethanolamine; PtdCho: phosphatidylcholine; DAG: sn-1,2-diacylglycerol; PKC: protein kinase C; Phosphoinositide-phospholipase C; Ins(1,4,5)P 3: inositol-1,4,5-trisphosphate; lyso-PtdOH: lysophosphatidic acid; InsP: inositol-4-phosphate; PtdInsP: phosphatidylinositol-4-phosphate; Lysophosphatidylcholine; Ischemia-reperfusion; lyso-PtdCho: lysophosphatidylcholine; PtdIns: phosphatidylinositol; PLC: phosphoinositide-phospholipase C; PLA 2: phospholipase A 2; PtdIns(4,5)P 2: phosphatidylinositol-4,5-bisphosphate; Phosphatidylinositol kinase; Ins(1,4)P 2: inositol-1,4-bisphosphate; Diabetes; SL: sarcolemma; Cardiac sarcolemma
• ISSN: 0005-2760; 0006-3002; 1879-145X; 1878-2434
• DOI: 10.1016/S0005-2760(97)00142-2

Although lysophosphatidylcholine (lyso-PtdCho) accumulates in the sarcolemmal (SL) membrane and alters its function during myocardial ischemia and diabetic cardiomyopathy, the effects of lyso-PtdCho on SL signalling processes have not yet been investigated. The present study was carried out to examine the actions of lyso-PtdCho on the rat heart SL membrane enzymes involved in the phosphoinositide pathway. Different lyso-PtdCho species (10 to 200 μM) inhibited the activities of both phosphatidylinositol kinase and phosphatidylinositol-4-phosphate kinase in the SL membrane in a concentration-dependent manner. The inhibitory potency of lyso-PtdCho compounds for phosphatidylinositol kinase was lyso-PtdCho plasmalogen >1-oleoyl-lyso-PtdCho >1-stearoyl-lyso-PtdCho >1-palmitoyl-lyso-PtdCho, and that for phosphatidylinositol-4-phosphate kinase was lyso-PtdCho plasmalogen >1-oleoyl-lyso-PtdCho >1-palmitoyl-lyso-PtdCho >1-stearoyl-lyso-PtdCho. The inhibitory effect of lyso-PtdCho on phosphatidylinositol-4-phosphate kinase was greater than that on phosphatidylinositol kinase. Lyso-PtdCho structural analogues, such as phosphatidylcholine, lysophosphatidic acid, lysophosphatidylethanolamine, L-α-glycerophosphate, oleate and phosphorylcholine, did not affect the phosphoinositide kinases, suggesting that the intact structure of lyso-PtdCho was required for the inhibition of the kinases. The detrimental action of lyso-PtdCho on PtdIns kinase was potentiated by acidosis. Unlike Ca 2+, ATP (0.1 and 4 mM) increased lyso-PtdCho-induced deactivation of the kinases. Both enzyme activities were found to be depressed in the ischemic-reperfused or diabetic hearts. None of the tested lyso-PtdCho species altered phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P 2) hydrolysis by SL phospholipase C. These results indicate that accumulation of lyso-PtdCho in the SL membrane under pathological conditions may diminish the availability of the PtdIns(4,5)P 2 substrate for the production of second messengers by receptor-linked phospholipase C.