Role of Phospholipase A2 Forms in Arachidonic Acid Mobilization and Eicosanoid Generation

Abstract

This chapter deals with Phospholipase A2 (PLA2), which plays a central role in lipid signaling, and consequently in a variety of inflammatory conditions. PLA2s have been systematically classified according to their nucleotide sequence. It begins with an account of PLA2 groups and their classification, which is being continuously updated. Following this, it presents an explanation of the cellular function of PLA2 in arachidonic acid (AA) release, stating that a myriad of agents that exert effects on cells via receptor-dependent or independent pathways elicits a series of signals that ultimately lead to increased PLA2 activity. During AA release cPLA2α and sPLA2 often act coordinately, the activity of one modifying the activity of the other, or vice versa. Depending on stimulation conditions, cPLA2α may modulate sPLA2 at a gene level or at the level of enzyme activity itself, although the mechanisms involved remain obscure. sPLA2 regulation of cPLA2α has also been found and investigated in detail in some instances. Finally, the study highlights that the group VIA PLA2 enzyme (iPLA2-VIA) is ubiquitously expressed in all types of cells, and has the potential to participate in AA release under some conditions. However, the role of iPLA2-VIA in AA release is controversial, which is mostly due to the fact that most studies implicating iPLA2-VIA have relied on the use of bromoenol lactone (BEL), a compound that manifests high selectivity for iPLA2-VIA in vitro, but whose selectivity in vivo is low.