Secreted phospholipase A 2 revisited

Abstract

Phospholipase A2 (PLA2) catalyses the hydrolysis of the sn-2 position of glycerophospholipids to yield fatty acids and lysophospholipids. So far, more than 30 enzymes that possess PLA2 or related activity have been identified in mammals. About one third of these enzymes belong to the secreted PLA2 (sPLA2) family, which comprises low molecular weight, Ca 2+ requiring, secreted enzymes with a His/Asp catalytic dyad. Individual sPLA2s display distinct localizations and enzymatic properties, suggesting their specialized biological roles. However, in contrast to intracellular PLA2s, whose roles in signal transduction and membrane homoeostasis have been well documented, the biological roles of sPLA2s in vivo have remained obscure until recently. Over the past decade, information fuelled by studies employing knockout and transgenic mice as well as specific inhibitors, in combination with lipidomics, has clarified when and where the different sPLA2 isoforms are expressed, which isoforms are involved in what types of pathophysiology, and how they exhibit their specific functions. In this review, we highlight recent advances in PLA2 research, focusing mainly on the physiological functions of sPLA2s and their modes of action on 'extracellular' phospholipid targets versus lipid mediator production. © The Authors 2011. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.