Human group IVC phospholipase A2 (cPLA2gamma). Roles in the membrane remodeling and activation induced by oxidative stress.
To create the unique properties of a certain cellular membrane, both the composition and the metabolism of membrane phospholipids are key factors. Phospholipase A(2) (PLA(2)), with hydrolytic enzyme activities at the sn-2 position in glycerophospholipids, plays critical roles in maintaining the phospholipid composition as well as producing bioactive lipid mediators. In this study we examined the contribution of a Ca(2+)-independent group IVC PLA(2) isozyme (cPLA(2)gamma), a paralogue of cytosolic PLA(2)alpha (cPLA(2)alpha), to phospholipid remodeling. The enzyme was localized in the endoplasmic reticulum and Golgi apparatus, as seen using green fluorescence fusion proteins. Electrospray ionization mass spectrometric analysis of membrane extracts revealed that overexpression of cPLA(2)gamma increased the proportion of polyunsaturated fatty acids in phosphatidylethanolamine, suggesting that the enzyme modulates the phospholipid composition. We also found that H(2)O(2) and other hydroperoxides induced arachidonic acid release in cPLA(2)gamma-transfected human embryonic kidney 293 cells, possibly through the tyrosine phosphorylation pathway. Thus, we propose that cPLA(2)gamma is constitutively expressed in the endoplasmic reticulum and plays important roles in remodeling and maintaining membrane phospholipids under various conditions, including oxidative stress.
Asai
Kenji
K
Department of Biochemistry and Molecular Biology, Faculty of Medicine, The University of Tokyo, Core Research for Evolutional Science and Technology of the Japan Science and Technology Corporation, Hongo 7-3-1, Bunkyo-ku, Japan.
Hirabayashi
Tetsuya
T
Houjou
Toshiaki
T
Uozumi
Naonori
N
Taguchi
Ryo
R
Shimizu
Takao
T
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D054513:Group IV Phospholipases A2; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D018384:Oxidative Stress; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054467:Phospholipases A2; D021241:Spectrometry, Mass, Electrospray Ionization
D004791:Enzyme Inhibitors; D016718:Arachidonic Acid; D006861:Hydrogen Peroxide; D010741:Phospholipases A; D054513:Group IV Phospholipases A2; D054467:Phospholipases A2