Induction of distinct sets of secretory phospholipase A2 in rodents during inflammation

Physiological Roles of Group X-secreted Phospholipase A2 in Reproduction, Gastrointestinal Phospholipid Digestion, and Neuronal Function

“…However, several studies employing more quantitative methods have shown that sPLA 2 -X is expressed in the testis and gastrointes-tinal tract much more abundantly than in immune organs (23,24). To ascertain the precise tissue distribution of sPLA 2 -X, we performed quantitative RT-PCR using a wide range of mouse tissues.…”

“…In line with its proinflammatory and proatherogenic potential, deficiency of sPLA 2 -X reduces the incidence of angiotensin-II-induced atherosclerosis and aneurysm in apoE Ϫ/Ϫ mice (20). It is notable that under physiological conditions, sPLA 2 -X is expressed in the testis and gastrointestinal tract at much higher levels than in other tissues (23,24). sPLA 2 -X is also uniquely located in peripheral neuronal fibers in several tissues and exerts a neuritogenic action on cultured neuronal cells in vitro (25,26).…”

The emerging role of group VI calcium-independent phospholipase A2 in releasing docosahexaenoic acid from brain phospholipids

“…On a broad level, the mammalian PLA 2 isoforms differ with respect to their tissue and cellular distribution, substrate specificities, and calcium requirements, and interested readers should consult other reviews for more details (36)(37)(38)(39)(40)(41), including PLA 2 nomenclature/classification (41,42). The isoforms identified in the brain to date include groups IVA, IVB, and IVC calcium-dependent cytosolic phospholipase A 2 (cPLA 2 ), groups IIA, IIC, IIE, V, and X calcium-dependent secretory phospholipase A 2 (sPLA 2 ), and groups VIA and VIB calcium-independent phospholipase A 2 (iPLA 2 ) (43)(44)(45)(46)(47)(48)(49). It is worth noting that the mouse strains C57BL/6, 129/Sv, and B10.RIII have a naturally occurring missense mutation in the gene encoding for the group IIA sPLA 2 (45,(50)(51)(52).…”

“…The isoforms identified in the brain to date include groups IVA, IVB, and IVC calcium-dependent cytosolic phospholipase A 2 (cPLA 2 ), groups IIA, IIC, IIE, V, and X calcium-dependent secretory phospholipase A 2 (sPLA 2 ), and groups VIA and VIB calcium-independent phospholipase A 2 (iPLA 2 ) (43)(44)(45)(46)(47)(48)(49). It is worth noting that the mouse strains C57BL/6, 129/Sv, and B10.RIII have a naturally occurring missense mutation in the gene encoding for the group IIA sPLA 2 (45,(50)(51)(52). As new proteins with PLA 2 -like activity are identified (53,54) and specific antibodies and reagents are developed, it is possible that more isoforms will be detected within the brain.…”

The First Potent Inhibitor of Mammalian Group X Secreted Phospholipase A2: Elucidation of Sites for Enhanced Binding

“…7,19,20 To date, very few inhibitors of the group X sPLA 2 have been reported, with the general sPLA 2 inhibitor YM-26734 being the most potent at 0.20 μM against the group X enzyme. 21 To this end, we recently determined the X-ray structure of the indole-based inhibitor Me-Indoxam bound to human group X sPLA 2 (hGX). 18 We now report the development of a potent indole-based inhibitor of hGX that was designed based on this structural information.…”