Emerging roles of secreted phospholipase A(2) enzymes: an update

Abstract

Phospholipase A(2) (PLA(2)) enzymes catalyze the hydrolysis of the sn-2 position of glycerophospholipids to produce free fatty acids and lysophospholipids. More than one third of the mammalian PLA(2) enzymes belong to the secreted PLA(2) (sPLA(2)) family, which consists of low molecular mass, Ca(2+)-requiring enzymes with a His-Asp catalytic dyad. Individual sPLA(2) enzymes exhibit unique tissue and cellular localizations and specific enzymatic properties, suggesting their distinct biological roles. The past decade has met a new era of the sPLA(2) research field toward deciphering their in vivo functions by developing several specific tools and methods. These include i) the production of transgenic and knockout mouse lines for several sPLA(2)s, ii) the development of specific analytical tools including the production of large amounts of recombinant sPLA(2) proteins, and iii) applying mass spectrometry lipidomics to unveil their specific enzymatic properties occurring in vivo. It is now obvious that individual sPLA(2)s are involved in diverse biological events through lipid mediator-dependent and -independent processes, act redundantly or non-redundantly in the context of physiology and pathophysiology, and may represent potential drug targets or novel bioactive molecules in certain situations. In this review, we will highlight the newest understanding of the biological roles of sPLA(2)s in the past few years.