[Secretory phospholipase A2 and its role in oxidative stress and inflammation].

Phospholipase A2 (EC 3.1.1.4, PLA2) belongs to the group of enzymes that catalyze the hydrolysis of the ester bond at position sn-2 of glycerophospholipids and hence generate free fatty acids including arachidonic acid. Under physiological conditions, PLA2 regulates the turnover of free fatty acids in membrane phospholipids, assuring membrane stability, fluidity and permeability, and thereby participates in regulation of transport processes through the cell membrane. Excessive release of free fatty acids by cytosolic and secretory PLA2 elevates the activity of cyclooxygenase 2 and the synthesis of prostaglandins, which can result in an enhance formation of free radicals and proinflammatory cytokines. Free arachidonic acid and its metabolites can reduce the level of the important endogenous antioxidant gluthatione. These changes can induce inflammatory processes and exert a neurotoxic effect in the brain. Increases in the activities of both cytosolic and secretory PLA2 isoforms were observed in various neurodegenerative diseases. The rise in the activity of the secretory PLA2 is usually much delayed compared to that in the cytosolic enzyme activity, but most likely it is the form that plays an important role in neurodegenerative diseases by enhancing oxidative stress and initiating inflammation.