III Phospholipase A₂
　　PLA₂ (EC3.1.1.4.) belongs to a family of enzymes that catalyze the cleavage of fatty acids from the sn-2 position of glycerophospholipids to produce free fatty acids and lysophospholipids.  PLA₂s participate in a wide variety of physiological processes, including phospholipid digestion, remodeling of cell membranes and host defense. They also take part in pathophysiological processes by producing precursors of various types of biologically active lipid mediators (Figure 3), such as prostaglandins (PGs), leukotrienes (LTs), thromboxanes (TXs) and platelet-acivating factor (PAF). In the mammalian system, more than 19 different isoforms of PLA₂ have been identified, and different PLA₂s have been shown to participate in physiological events related to cell injury, inflammation, and apoptosis. According to their biochemical features such as cellular localization, requirement of Ca²⁺, substrate specificity and the primary structure, these PLA₂s are classified into several families, including low molecular weight secretory PLA₂ (sPLA₂), Ca²⁺-sensitive arachidonoyl-specific 85-kDa cytosolic PLA₂ (cPLA₂), Ca²⁺-independent PLA₂ (iPLA₂), and PAF-acetylhydrolase. In the mammalian CNS, five sPLA₂ (IIA, IIC, IIF, V and XII), cPLA₂ (IV) and iPLA₂ (VI) have been detected (Table 2).
　　sPLA₂-IIA possesses an intramolecular disulfide bond between Cys50 and Cys137, as well as an amino acid C-terminal extension, and sPLA₂-IIA does not have a propeptide. sPLA₂-IIA is found in many cells and tissues and its expression is modulated by various inflammatory cytokines, such as interleukin 1ß (IL-1β) and tumor necrosis factor-α (TNF-α) in astrocytes (Figure 2). These inflammatory cytokines are increased by cerebral ischemia, leading to the expression of sPLA₂-IIA in the ischemic brain. The cortical sPLA₂ activity is significantly elevated in response to focal cerebral ischemia. sPLA₂-IIA is induced in the cortex, in which the ischemic core and the penumbra coexist. The sPLA₂ inhibitor reduces the elevated PLA₂ activity completely and the infarct volume significantly in the cortex. The inhibitor ameliorated occlusion-induced inflammation and neurodegeneration in the penumbra, suggesting that sPLA₂ might play an important role in apoptosis in the penumbra. As shown in Figure 3, sPLA₂-IIA potentiates Ca²⁺ influx through L-VSCC and glutamate receptors, and induces neuronal cell death via apoptosis. Although sPLA₂-IB has not yet been detected in the brain, high-affinity binding sites of sPLA₂-IB exist on the plasma membrane of cortical neurons. sPLA₂-IB also induces the excess influx of Ca²⁺ into neurons via L-VSCC, and subsequently neuronal cell death via apoptosis. It is unclear whether the high-affinity binding sites of sPLA₂-IB are sPLA₂ receptor or not (Figure 3).