CONTROL OF ARACHIDONIC ACID LEVELS BY CERAMIDE 1-PHOSPHATE AND ITS IMPACT IN CELL BIOLOGY

Lipids play major roles in cell biology. Some of them are essential components of cell membranes and energy stores, whereas others function as signaling molecules. In particular, arachidonic acid (AA) and AA-containing lipids have been involved in the regulation of vital cellular functions including cell proliferation, survival, chemotaxis, and neurological development. In addition, AA has been shown to protect against the toxic effects of palmitate, and to modulate insulin signaling and prevent insulin resistance (the latter action involves its conversion to epoxyeicosatrienoic acid). Also, it is well established that AA is the precursor of prostaglandins, some of which play major roles in inflammation. More recently, AA has been established as a reliable marker of cardiovascular disease. From these findings, it is clear that AA function and metabolism are key events for regulation of cell activation, and that it plays critical roles in disease. A major source of AA in cells is membrane glycerophospholipids, many of which bear AA in the second position of their glycerol moiety. AA can be released upon stimulation of phospholipase A₂ (PLA₂) activity by a number of agonists, thereby becoming available for further metabolism to eicosanoids. A recently described activator of the cytosolic form of PLA₂ (cPLA₂), a major PLA₂ for AA production, is ceramide 1-phosphate (C1P). This phosphosphingolipid has pro-inflammatory properties and was previously described as potent mitogen and inhibitor of apoptosis. Therefore, AA and C1P regulate crucial pathophysiological processes.