Recent progress in phospholipase A2 research: From cells to animals to humans

Mammalian genomes encode genes for more than 30 phospholipase A(2)s (PLA(2)s) or related enzymes, which are subdivided into several classes including low-molecular-weight secreted PLA(2)s (sPLA(2)s), Ca2+-dependent cytosolic PLA(2)s (cPLA(2)s), Ca2+-independent PLA(2)s (iPLA(2)s), platelet-activating factor acetylhydrolases (PAF-AHs), lysosomal PLA(2)s, and a recently identified adipose-specific PLA. Of these, the intracellular cPLA(2) and iPLA(2) families and the extracellular sPLA(2) family are recognized as the "big three". From a general viewpoint, cPLA(2)alpha (the prototypic cPLA(2)) plays a major role in the initiation of arachidonic acid metabolism, the iPLA(2) family contributes to membrane homeostasis and energy metabolism, and the sPLA(2) family affects various biological events by modulating the extracellular phospholipid milieus. The cPIA(2) family evolved along with eicosanoid receptors when vertebrates first appeared, whereas the diverse branching of the iPLA(2) and sPLA(2) families during earlier eukaryote development suggests that they play fundamental roles in life-related processes. During the past decade, data concerning the unexplored roles of various PLA(2) enzymes in pathophysiology have emerged on the basis of studies using knockout and transgenic mice, the use of specific inhibitors, and information obtained from analysis of human diseases caused by mutations in PLA(2) genes. This review focuses on current understanding of the emerging biological functions of PLA(2)s and related enzymes. (C) 2010 Elsevier Ltd. All rights reserved.