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 μM) 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, CK2, PI3K, p38, or ERK inhibitory activities. Quercetin (10-40 μM), 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.
|Original language||English (US)|
|Number of pages||8|
|Journal||Free Radical Biology and Medicine|
|State||Published - Sep 15 2005|
Bibliographical noteFunding Information:
This work was supported by the Mary Johnson Research Fund, National Institutes of Health Grant HL58013 (R.J.W., D.K.S.), and in part by the German Federal Department of Education and Research (BMBF Network “Nutrition and Atherosclerosis;” H.S.).
- Free radicals
- Heme oxygenase