Signaling role for lysophosphatidylcholine acyltransferase 3 in receptor-regulated arachidonic acid reacylation reactions in human monocytes.
Cellular availability of free arachidonic acid (AA) is an important step in the production of pro- and anti-inflammatory eicosanoids. Control of free AA levels in cells is carried out by the action of phospholipase A2s and lysophospholipid acyltransferases, which are responsible for the reactions of deacylation and incorporation of AA from and into the sn-2 position of phospholipids, respectively. In this work, we have examined the pathways for AA incorporation into phospholipids in human monocytes stimulated by zymosan. Our data show that stimulated cells exhibit an enhanced incorporation of AA into phospholipids that is not secondary to an increased availability of lysophospholipid acceptors due to phospholipase A2 activation but rather reflects the receptor-regulated nature of the AA reacylation pathway. In vitro activity measurements indicate that the receptor-sensitive step of the AA reacylation pathway is the acyltransferase using lysophosphatidylcholine (lysoPC) as acceptor, and inhibition of the enzyme lysoPC acyltransferase 3 by specific small interfering RNA results in inhibition of the stimulated incorporation of AA into phospholipids. Collectively, these results define lysoPC acyltransferase 3 as a novel-signal-regulated enzyme that is centrally implicated in limiting free AA levels in activated cells.
Pérez-Chacón
Gema
G
Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas, Valladolid, Spain.
Astudillo
Alma M
AM
Ruipérez
Violeta
V
Balboa
María A
MA
Balsinde
Jesús
J
D008243:1-Acylglycerophosphocholine O-Acyltransferase / Q000378:metabolism / Q000502:physiology*; D000215:Acylation; D016718:Arachidonic Acid / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D009000:Monocytes / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D015398:Signal Transduction; D015054:Zymosan / Q000494:pharmacology
D010743:Phospholipids; D016718:Arachidonic Acid; D015054:Zymosan; D008243:1-Acylglycerophosphocholine O-Acyltransferase; C543069:LPCAT3 protein, human