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 ofcell membranes and energy stores, whereas others function as signaling molecules. Inparticular, arachidonic acid (AA) and AA-containing lipids have been involved in theregulation of vital cellular functions including cell proliferation, survival, chemotaxis,and neurological development. In addition, AA has been shown to protect against thetoxic effects of palmitate, and to modulate insulin signaling and prevent insulin resistance(the latter action involves its conversion to epoxyeicosatrienoic acid). Also, it is wellestablished that AA is the precursor of prostaglandins, some of which play major roles ininflammation. More recently, AA has been established as a reliable marker ofcardiovascular disease. From these findings, it is clear that AA function and metabolismare 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 whichbear AA in the second position of their glycerol moiety. AA can be released uponstimulation of phospholipase A₂ (PLA₂) activity by a number of agonists, therebybecoming available for further metabolism to eicosanoids. A recently described activatorof the cytosolic form of PLA₂ (cPLA₂), a major PLA₂ for AA production, is ceramide 1-phosphate (C1P). This phosphosphingolipid has pro-inflammatory properties and waspreviously described as potent mitogen and inhibitor of apoptosis. Therefore, AA andC1P regulate crucial pathophysiological processes.