Regulation and inhibition of phospholipase A2

被引:505
作者
Balsinde, J [1 ]
Balboa, MA
Insel, PA
Dennis, EA
机构
[1] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA
[2] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA
关键词
arachidonic acid; eicosanoid; lipid second messenger; inflammation; chemical inhibition; antisense inhibition;
D O I
10.1146/annurev.pharmtox.39.1.175
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
In recent years, there has been great interest in the study of phospholipid metabolism in intact cell systems. Such an interest arises mainly from the discovery that cellular membrane phospholipids serve not only in structural roles, but are also reservoirs of preformed second messenger molecules with key roles in cellular signaling. These second messenger molecules are generated by agonist-induced activation and secretion of intracellular and extracellular phospholipases, respectively, i.e, enzymes that cleave ester bonds within phospholipids. Prominent members of the large collection of signal-activated phospholipases are the phospholipase A(2)s. These enzymes hydrolyze the sn-2 ester bond of phospholipids, releasing a free fatty acid and a lysophospholipid, both of which may alter cell function. In addition to its role in cellular signaling, phospholipase At has recently been recognized to be involved in a wide number of pathophysiological situations, ranging from systemic and acute inflammatory conditions to cancer. A growing number of pharmacologic inhibitors will help define the role of particular phospholipase A(2)s in signaling cascades.
引用
收藏
页码:175 / 189
页数:15
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