Cellular Function of Calcium-Independent Phospholipase A2

Abstract

The catalytic activity of calcium-independent phospholipase A 2 (iPLA 2 ), which is classified as a group VI PLA 2 , is regulated by protein kinase C, calmodulin, and others such as reactive oxygen species. Numerous findings have shown that iPLA 2 is involved in stimulus-induced arachidonic acid release and lysophospholipid generation, although the participation is dependent upon the cell type and stimulus. The catalytic action of iPLA 2 is known to be responsible for phospholipid remodeling as a housekeeping function. However, it has been widely accepted that arachidonic acid and lysophospholipid generated by iPLA 2 act as a signaling molecule in cellular functions. Those include eicosanoid production, glucose-induced insulin secretion, Fas-induced apoptosis, cellular proliferation, membrane traffic in fusion, contribution to myocardial ischemia, and others. In this review, the functional role of iPLA 2 in cellular responses upon stimulation is the focus.

Fatty Acid Signaling in the β-Cell and Insulin Secretion

“…AA release depends on ␤-cell metabolism of glucose (76), and it has been shown that exogenous AA is capable of causing a rise in cytosolic Ca 2ϩ (77). Importantly, AA is substrate for the synthesis of eicosanoid signaling molecules (78). Lysophosphatidic acids, produced in addition to AA by the action of phospholipase A isoforms on membrane phospholipids, also have signaling actions (78).…”

“…Importantly, AA is substrate for the synthesis of eicosanoid signaling molecules (78). Lysophosphatidic acids, produced in addition to AA by the action of phospholipase A isoforms on membrane phospholipids, also have signaling actions (78). Although it was thought that glucose-stimulated AA release is from hydrolysis of membrane phospholipids (75)(76)(77)(78)(79), another possibility is that it is from hydrolysis of TG within the TG/FFA cycling pathway.…”

“…Lysophosphatidic acids, produced in addition to AA by the action of phospholipase A isoforms on membrane phospholipids, also have signaling actions (78). Although it was thought that glucose-stimulated AA release is from hydrolysis of membrane phospholipids (75)(76)(77)(78)(79), another possibility is that it is from hydrolysis of TG within the TG/FFA cycling pathway. It is noteworthy that in many cell types (80), and in INS832/13 cells (M.S.R.M., M.P., unpublished data), externally added AA is incorporated into both TG and phospholipids.…”

Integration of cytokine biology and lipid metabolism in stroke

“…cPLA 2 preferentially cleaves ArAc at the sn-2 position of PC and forms lyso-PC, whereas sPLA 2 s show no fatty acid preference and act on a broader range of phospholipids (45,46). iPLA 2 s also are not selective for ArAc and are considered to be involved primarily in membrane remodeling (47,48). Full activation of cPLA 2 requires binding of Ca 2+ for translocation from cytosol to the phospholipid membrane and phosphorylation of specific serine residues (49).…”

Melanoma-Induced Endothelial Cell Growth Involves Phospholipase A2 and COX2 Upregulation

“…Among the PLA 2 s is an 85 kDa cPLA 2 that requires Ca 2+ for catalysis, and a calcium independent PLA 2 , iPLA 2 β, for which several potential functions have been proposed, including a housekeeping role in phospholipid remodeling and a signaling role in cell growth, apoptosis, secretion, inflammation, and oxidant-induced cell injury (Chakraborti, 2003). A number of observations that iPLA 2 has a functional role in cellular signaling in addition to its roles in AA release and phospholipid remodeling have been reported (Akiba & Sato, 2004). iPLA 2 mediates the phosphorylation of transcription factors through a PKAdependent pathway (Martinson et al, 2003).…”