PHOSPHATIDYLCHOLINE IS A MAJOR SOURCE OF PHOSPHATIDIC-ACID AND DIACYLGLYCEROL IN ANGIOTENSIN-II-STIMULATED VASCULAR SMOOTH-MUSCLE CELLS

被引:94
作者
LASSEGUE, B
ALEXANDER, RW
CLARK, M
AKERS, M
GRIENDLING, KK
机构
[1] Emory University School of Medicine, Division of Cardiology, Atlanta
关键词
D O I
10.1042/bj2920509
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In cultured vascular smooth-muscle cells. angiotensin II produces a sustained formation of diacylglycerol (DG) and phosphatidic acid (PtdOH). Since the fatty acid composition of these molecules is likely to determine their efficacy as second messengers, it is important to ascertain the phospholipid precursors and the biochemical pathways from which they are produced. Our experiments suggest that phospholipase D (PLD)-mediated phosphatidylcholine (PtdCho) hydrolysis is the major source of both DG and PtdOH during the late signalling phase. First, in cells labelled with [H-3]myristate, which preferentially labels PtdCho, formation of [H-3]PtdOH precedes formation of [H-3]DG. Second, in contrast with phospholipase C (PLC) activation, DG mass accumulation is dependent on extracellular Ca2+. Similarly, DG mass accumulation is not attenuated by protein kinase C activation, which we have previously shown to inhibit the phosphoinositide-specific PLC. Third, the fatty acid composition of late-phase DG and PtdOH more closely resembles that of PtdCho than that of phosphatidylinositol. Finally, in cells labelled for a short time with [H-3]glycerol, the radioactivity incorporated into [H-3]DG and PtdOH was greater than that incorporated into PtdIns, but not into PtdCho. We found no evidence that synthesis de novo or phosphatidylethanolamine breakdown contributes to sustained DG and PtdOH formation. Thus, in angiotensin 11-stimulated cultured vascular smooth-muscle cells, PLD-mediated PtdCho hydrolysis is the major-source of sustained DG and PtdOH, whereas phosphoinositide breakdown is a minor contributor. Furthermore, PtdOH phosphohydrolase, which determines the relative levels of DG and PtdOH, appears to be regulated by protein kinase C. These results have important implications for the role of these second messengers in growth and contraction.
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页码:509 / 517
页数:9
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