Apigenin decreases hemin-mediated heme oxygenase-1 induction

Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Free Radical Biology and Medicine (Impact Factor: 5.74). 10/2005; 39(6):711-8. DOI: 10.1016/j.freeradbiomed.2005.01.020
Source: PubMed


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.

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    • "In astrocytes, increasing HO1 expression by adenoviral gene transfer before heme exposure attenuates oxidative stress and cell death (Chen and Regan, 2005). In fibroblasts, a moderate overexpression of HO1 is protective, whereas uncontrolled (beyond threshold) HO1 levels can be detrimental (Abate et al, 2005). "
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