Role of calcium-independent phospholipases (iPLA(2)) in phosphatidylcholine metabolism.
The proposed role of calcium-independent phospholipase A(2) (iPLA(2)) in membrane phospholipid homeostasis was tested by examining the perturbation of phosphatidylcholine metabolism by enzyme overexpression. There are alternatively spliced forms of murine iPLA(2) that were widely expressed in mouse tissues: a long form containing exon-9 that is membrane-associated and a short form lacking exon-9 that is distributed between the membrane and cytosolic fractions. Enforced expression of either iPLA(2) isoform led to a significant increase in intracellular free fatty acid, lysophosphatidylcholine, and GPC without a concomitant increase in the incorporation of either exogenous arachidonic acid or choline. The accumulation of lysophosphatidylcholine in iPLA(2)-expressing cells illustrates the limited capacity of cells for reacylation and degradation of lysophospholipids. Since iPLA(2) overexpression did not accelerate either phospholipid remodeling or phosphatidylcholine synthesis, this enzyme does play a determinant (rate-controlling?) role in either of these cellular processes.
Chiu
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Protein Science Division, St. Jude Children's Research Hospital, Memphis, Tennessee 38105-2794, USA.
Jackowski
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D017398:Alternative Splicing; D000818:Animals; D019556:COS Cells; D005091:Exons; D005227:Fatty Acids / Q000378:metabolism; D054522:Group VI Phospholipases A2; D015151:Immunoblotting; D008244:Lysophosphatidylcholines / Q000378:metabolism; D051379:Mice; D010713:Phosphatidylcholines / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism / Q000502:physiology*; D010957:Plasmids / Q000378:metabolism; D020033:Protein Isoforms; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013347:Subcellular Fractions; D014018:Tissue Distribution; D014162:Transfection
D005227:Fatty Acids; D008244:Lysophosphatidylcholines; D010713:Phosphatidylcholines; D020033:Protein Isoforms; D010741:Phospholipases A; D054522:Group VI Phospholipases A2; C516476:Pla2g6 protein, mouse