Apigenin decreases hemin-mediated heme oxygenase-1 induction.
Hemin is a strong inducer of heme oxygenase-1 (HO-1) expression in vitro and in vivo. Whereas moderate overexpression of HO-1 is protective against oxidative stress, uncontrolled levels of HO-1 can be detrimental. Therefore, we evaluated the effects of apigenin (APG), a flavonoid involved in a number of phosphorylation pathways and also known to inhibit inducible genes, such as iNOS and COX-2, on HO-1 expression. Incubation of mouse embryonic fibroblasts with APG (5--40 microM) decreased hemin-induced HO-1 protein and mRNA expression. APG also reduced the induction of HO-1 promoter activity, as assessed by bioluminescence imaging, in NIH3T3 cells transfected with the 15-kb HO-1 promoter fused with the reporter gene luciferase (HO-1-luc). Furthermore, through the use of specific inhibitors, APG's effect was found to be unrelated to its PKC, CK 2, PI 3 K, p38, or ERK inhibitory activities. Quercetin (10--40 microM), also a flavonoid, also inhibited hemin-induced HO-1 expression. Additionally, in vivo studies using HO-1-luc transgenic mice showed that APG (50 mg/kg) decreased hemin-induced HO activity and HO-1 protein expression in the liver. These results suggest that hemin-induced HO-1 expression can be attenuated by flavonoids, such as APG.
Abate
Aida
A
Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Yang
Guang
G
Wong
Ronald J
RJ
Schroder
Henning
H
Stevenson
David K
DK
Dennery
Phyllis A
PA
D000199:Actins / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000737:chemistry; D047310:Apigenin / Q000378:metabolism / Q000502:physiology*; D015152:Blotting, Northern; D002470:Cell Survival; D003513:Cycloheximide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D005419:Flavonoids / Q000737:chemistry; D005609:Free Radicals; D017930:Genes, Reporter; D006427:Hemin / Q000737:chemistry*; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D041681:NIH 3T3 Cells; D018384:Oxidative Stress; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
D000199:Actins; D000975:Antioxidants; D004791:Enzyme Inhibitors; D005419:Flavonoids; D005609:Free Radicals; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D006427:Hemin; D047310:Apigenin; D003513:Cycloheximide; D008156:Luciferases