Peroxisome proliferators attenuate free arachidonic acid pool in the kidney through inducing lysophospholipid acyltransferases.
Attenuating effects of peroxisome proliferators on the concentration of free arachidonic acid by inducing 1-acyl-2-lysophospholipid acyltransferases in the kidney were studied. The administration of the three structurally dissimilar peroxisome proliferators, 2-(4-chlorophenoxy)-2-methylpropionic acid (clofibric acid), di(2-ethylhexyl)phthalate, and 2,2'-(decamethylenedithio)diethanol, to rats or mice considerably increased the activities of microsomal 1-acylglycerophosphoethanolamine acyltransferase (LPEAT), 1-acylglycerophosphoinositol acyltransferase (LPIAT), 1-acylglycerophosphoserine acyltransferase (LPSAT), and 1-acylglycerophosphocholine acyltransferase (LPCAT), and the mRNA level of LPCAT3, but not the mRNA level of LPCAT1, LPCAT4, or LPEAT1, in the kidney and the liver. The proportions of arachidonic acid in phospholipids in renal microsomes are rather high for the low proportion of arachidonic acid in free fatty acids in renal microsomes of control rats. The treatment of rats with clofibric acid attenuated the concentration and the proportion of free arachidonic acid to about a half; nevertheless the treatment lowered slightly the proportions of arachidonic acid in phospholipids other than phosphatidylcholine. These results indicate that peroxisome proliferators upregulate the four 1-acyl-2-lysophospholipid acyltransferases of the kidney and, and the induced 1-acyl-2-lysophospholipid acyltransferases seem to play a physiologically crucial contribution in attenuating the pool of free arachidonic acid in the kidney.
Yamazaki
Tohru
T
Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama, Japan.
Hirose
Akihiko
A
Sakamoto
Takeshi
T
Okazaki
Mari
M
Mitsumoto
Atsushi
A
Kudo
Naomi
N
Kawashima
Yoichi
Y
D008243:1-Acylglycerophosphocholine O-Acyltransferase / Q000096:biosynthesis*; D000217:Acyltransferases / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D002995:Clofibric Acid / Q000494:pharmacology; D004051:Diethylhexyl Phthalate / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D005233:Fatty Alcohols / Q000494:pharmacology*; D007668:Kidney / Q000201:enzymology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008861:Microsomes / Q000187:drug effects*; D008954:Models, Biological; D020025:Peroxisome Proliferators / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D005233:Fatty Alcohols; D020025:Peroxisome Proliferators; D012333:RNA, Messenger; C004568:tiadenol; D016718:Arachidonic Acid; D002995:Clofibric Acid; D004051:Diethylhexyl Phthalate; C053809:1-acylglycerophosphoethanolamine acyltransferase; D000217:Acyltransferases; C038660:1-acylglycerophosphorylinositol acyltransferase; C025461:1-acylglycerophosphoserine acyltransferase; D008243:1-Acylglycerophosphocholine O-Acyltransferase