Protection against oxidative stress-induced cell death by intracellular platelet-activating factor-acetylhydrolase II.
Platelet-activating factor-acetylhydrolase (PAF-AH), which removes the acetyl group at the sn-2 position of PAF, is distributed widely in tissues and plasma. Tissue cytosol contains at least two types of PAF-AH, isoforms Ib and II. Isoform Ib is a tertiary G-protein complex-like heterotrimeric enzyme that is involved in brain development such as formation of the brain cortex. Isoform II (PAF-AH(II)), however, is a 40-kDa monomer and has an amino acid sequence that exhibits a 41% identity with that of plasma PAF-AH. Although PAF-AH(II) preferentialy hydrolyzes oxidized phospholipids as well as PAF in vitro, the function of this enzyme has not, as yet, been elucidated. Here, we report that PAF-AH(II) functions as an anti-oxidant phospholipase. PAF-AH(II) was found to be an N-myristoylated enzyme that has never been reported among lipases and phospholipases. In MDBK cells treated with oxidants, PAF-AH(II) translocated from cytosol to membranes within 20 min, whereas in cells treated with anti-oxidants, it translocated, conversely, from membranes to cytosol. Overexpression of PAF-AH(II) in Chinese hamster ovary-K1 cells suppressed oxidative stress-induced cell death, which occurs by apoptosis. These findings suggest that intracellular PAF-AH(II) translocates between cytosol and membranes in response to a redox state of the cell and protects the cell against oxidative stress most probably by hydrolyzing oxidized phospholipids.
Matsuzawa
A
A
Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113, Japan.
Hattori
K
K
Aoki
J
J
Arai
H
H
Inoue
K
K
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000595:Amino Acid Sequence; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001692:Biological Transport; D016466:CHO Cells; D002417:Cattle; D016923:Cell Death; D002462:Cell Membrane / Q000378:metabolism; D006224:Cricetinae; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D019814:Myristic Acid / Q000378:metabolism; D018384:Oxidative Stress; D010740:Phospholipases / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism
D000975:Antioxidants; D010743:Phospholipids; D019814:Myristic Acid; D010740:Phospholipases; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase