ENHANCED HYDROLYSIS OF PHOSPHATIDYLCHOLINE BY HUMAN GROUP-II NONPANCREATIC SECRETED PHOSPHOLIPASE A(2) AS A RESULT OF INTERFACIAL ACTIVATION BY SPECIFIC ANIONS - POTENTIAL ROLE OF CHOLESTEROL SULFATE

被引:31
作者
KINKAID, AR [1 ]
WILTON, DC [1 ]
机构
[1] UNIV SOUTHAMPTON, DEPT BIOCHEM, SOUTHAMPTON SO16 7PX, HANTS, ENGLAND
关键词
D O I
10.1042/bj3080507
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
The extracellular concentration of the Group II human nonpancreatic secreted phospholipase A(2) (hnpsPLA(2)) is elevated in a variety of inflammatory disorders. This enzyme is remarkable because it demonstrates almost zero activity with egg phosphatidylcholine (PC) or synthetic dioleoyl-phosphatidylcholine (DOPC) as substrate, but expresses high activity with the anionic phospholipid dioleoyl-phosphatidylglycerol (DOPG), a feature shared with the Group II enzyme from rat liver. The presence of certain membrane-bound anions can enhance hydrolysis of PC by the mammalian secreted PLA(2)s. In this study the ability of various non-polar anions to stimulate DOPC hydrolysis by secreted PLA(2)s has been investigated. The naturally occurring membrane anion, cholesterol sulphate, was particularly effective in stimulating the hydrolysis of both DOPC and also 1-stearoyl-2-arachidonyl phosphatidylcholine by hnpsPLA(2). Activation of DOPC hydrolysis was also achieved with dioleoylphosphatidylserine (DOPS); however, DOPS was less effective than cholesterol sulphate. In contrast, the dianion dioleoylphosphatidic acid, a known activator of pig pancreatic PLA(2), failed to activate the human enzyme. It remains to be established whether cell plasma-membrane hydrolysis by extracellular hnpsPLA(2) can be activated in vivo by the presence of suitable membrane anions such as cholesterol sulphate and thus promote an inflammatory response within the cell.
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页码:507 / 512
页数:6
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