The lipid peroxidation end-product 4-HNE induces COX-2 expression through p38MAPK activation in 3T3-L1 adipose cell.
Oxidative stress and low grade chronic inflammation are increased in accumulating fat. Our objective was to test whether 4-hydroxynonenal (4-HNE), an end-product of lipid peroxidation, affects cyclooxygenases in 3T3-L1 adipose cells. 4-HNE increased COX-2 mRNA and protein expression and p38MAP-kinase phosphorylation in a dose-dependent manner. Pretreatment of 3T3-L1 cells by a selective inhibitor of p38MAPK (PD 169316) abolished 4-HNE and glucose oxidase induced COX-2 expression. Our results show that oxidative stress induces COX-2 expression through the production of 4-HNE which activates p38MAPKinase, suggesting that 4-HNE links oxidative stress and chronic inflammation through the activation of cyclooxygenase.
Zarrouki
B
B
Université de Lyon, F-69008 France.
Soares
A F
AF
Guichardant
M
M
Lagarde
M
M
Géloën
A
A
D016475:3T3 Cells; D017667:Adipocytes / Q000187:drug effects / Q000201:enzymology*; D000447:Aldehydes / Q000494:pharmacology*; D000818:Animals; D051546:Cyclooxygenase 2 / Q000235:genetics*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D015237:Dinoprost / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D015227:Lipid Peroxidation; D051379:Mice; D018384:Oxidative Stress; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D000447:Aldehydes; D015853:Cysteine Proteinase Inhibitors; D012333:RNA, Messenger; D015237:Dinoprost; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D048051:p38 Mitogen-Activated Protein Kinases; C027576:4-hydroxy-2-nonenal; D015232:Dinoprostone