Integrated Lipidomics in the Secreted Phospholipase A₂ Biology

Abstract: Mammalian genomes encode genes for more than 30 phospholipase A₂s (PLA₂s) or related enzymes, which are subdivided into several subgroups based on their structures, catalytic mechanisms, localizations and evolutionary relationships. More than one third of the PLA₂ enzymes belong to the secreted PLA₂ (sPLA₂) family, which consists of low-molecular-weight, Ca²⁺-requiring extracellular enzymes, with a His-Asp catalytic dyad. Individual sPLA₂ isoforms exhibit unique tissue and cellular localizations and enzymatic properties, suggesting their distinct pathophysiological roles. Recent studies using transgenic and knockout mice for several sPLA₂ isoforms, in combination with lipidomics approaches, have revealed their distinct contributions to various biological events. Herein, we will describe several examples of sPLA₂-mediated phospholipid metabolism in vivo, as revealed by integrated analysis of sPLA₂ transgenic/knockout mice and lipid mass spectrometry. Knowledge obtained from this approach greatly contributes to expanding our understanding of the sPLA₂ biology and pathophysiology.