MASS-SPECTROMETRIC IDENTIFICATION AND QUANTITATION OF ARACHIDONATE-CONTAINING PHOSPHOLIPIDS IN PANCREATIC-ISLETS - PROMINENCE OF PLASMENYLETHANOLAMINE MOLECULAR-SPECIES

被引:76
作者
RAMANADHAM, S
BOHRER, A
MUELLER, M
JETT, P
GROSS, RW
TURK, J
机构
[1] WASHINGTON UNIV,SCH MED,DEPT PATHOL,ST LOUIS,MO 63110
[2] WASHINGTON UNIV,SCH MED,DEPT MED,DIV BIOORGAN CHEM & MOLEC PHARMACOL,ST LOUIS,MO 63110
[3] WASHINGTON UNIV,SCH MED,DEPT CHEM,ST LOUIS,MO 63110
[4] WASHINGTON UNIV,SCH MED,DEPT MOLEC BIOL & PHARMACOL,ST LOUIS,MO 63110
关键词
D O I
10.1021/bi00071a009
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
D-Glucose induces insulin secretion from beta-cells of pancreatic islets by processes involving glycolytic metabolism and generation of ATP. Glucose also induces hydrolysis of beta-cell membrane phospholipids and accumulation of nonesterified arachidonate, which facilitates Ca2+ entry and the rise in beta-cell Ca2+ concentration that is a critical signal in the induction of insulin secretion. Glucose-induced hydrolysis of arachidonate from beta-cell phospholipids is mediated in part by an ATP-stimulated, Ca2+-indePendent (ASCI)-phospholipase A2 (PLA2), which, in vitro, prefers plasmalogen over diacylphospholipid substrates, but it is not known whether islets contain plasmalogens. We have identified and quantitated the major species of arachidonate-containing phospholipids in pancreatic islets by high-performance liquid chromatographic and mass spectrometric analyses. Arachidonate has been found to constitute 30% of the total islet glycerolipid fatty acyl mass. Ethanolamine phospholipids contain 30% of total islet arachidonate, and 44% of that amount resides in three plasmenylethanolamine molecular species with residues of palmitic, oleic, or stearic aldehydes in the sn-I position. These endogenous islet plasmenylethanolamine species are hydrolyzed more rapidly than phosphatidylethanolamine species by islet ASCI-PLA2 in vitro and are also hydrolyzed in intact islets stimulated with secretagogues. ASCI-PLA2-catalyzed hydrolysis of islet plasmenylethanolamine species in vitro is inhibited by a selective haloenol lactone suicide substrate (HELSS) which is sterically similar to plasmalogens, and HELSS also inhibits all temporal phases of both eicosanoid release and insulin secretion from secretagogue-stimulated pancreatic islets. Islet beta-cell ASCI-PLA2-catalyzed hydrolysis of arachdionate from endogenous plasmenylethanolamine substrates may be an intermediary biochemical event in the induction of insulin secretion.
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页码:5339 / 5351
页数:13
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