Mechanism of heme oxygenase-1 gene induction by quercetin in rat aortic smooth muscle cells.
We previously reported that adenovirus-mediated gene transfer of heme oxygenase-1 (HO-1) inhibits the development of atherosclerosis in apolipoprotein E-deficient mice. This finding implies that HO-1 induction is beneficial for protecting blood vessels. We also found that quercetin, a common polyphenolic compound in foods of plant origin, induces HO-1 expression in RAW264.7 cells. This study was aimed at examining the potency of quercetin as a HO-1 inducer and its regulation in rat aortic smooth muscle cells (RASMCs). We showed that quercetin-induced HO-1 production was in time- and dose-dependent fashions, and that this regulation occurred at both transcription and translation levels. Quercetin increased p38 mitogen-activated protein kinase (p38MAPK), but inhibited extracellular signal-regulated kinase in RASMCs. The level of quercetin-induced HO-1 expression was attenuated by SB202190 (a p38MAPK inhibitor). Taken together from the data in this study, we suggest that quercetin induced HO-1 expression, at least in part, through p38MAPK.
Lin
Hui-Chen
HC
Department of Ophthalmology, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei Medical University, Taiwan.
Cheng
Tzu-Hurng
TH
Chen
Yen-Chou
YC
Juan
Shu-Hui
SH
D000818:Animals; D015152:Blotting, Northern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000502:physiology; D006168:Guinea Pigs; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D051547:Heme Oxygenase-1; D007093:Imidazoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D014176:Protein Biosynthesis / Q000187:drug effects / Q000235:genetics; D011725:Pyridines / Q000494:pharmacology; D011794:Quercetin / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics; D015533:Transcriptional Activation; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
D007093:Imidazoles; D011725:Pyridines; D012333:RNA, Messenger; D003609:Dactinomycin; D003513:Cycloheximide; D011794:Quercetin; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D048051:p38 Mitogen-Activated Protein Kinases; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole