Apigenin decreases hemin-mediated heme oxygenase-1 induction
Apigenin decreases hemin-mediated heme oxygenase-1 induction
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DOI：
10.1016/j.freeradbiomed.2005.01.020
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发表时间：
2005-09-15
影响因子：
7.4
通讯作者：
Dennery, PA
中科院分区：
文献类型：
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作者：
Abate, A;Yang, G;Dennery, PA
氯化血红素是体外和体内血红素加氧酶-1 (HO-1) 表达的强诱导剂。虽然 HO-1 的适度过度表达可以防止氧化应激，但 HO-1 水平不受控制可能是有害的。因此，我们评估了芹菜素 (APG) 的影响，芹菜素是一种黄酮类化合物，参与多种磷酸化途径，并且还已知可抑制诱导基因（如 NOS 和 COX-2）对 HO-1 表达的影响。将小鼠胚胎成纤维细胞与APG (5-40μl)一起孵育可降低氯高铁血红素诱导的HO-1蛋白和mRNA表达。通过生物发光成像评估，在用与报告基因荧光素酶融合的 15-kb HO-1 启动子 (HO-1-luc) 转染的 NIH3T3 细胞中，APG 还降低了 HO-1 启动子活性的诱导。此外，通过使用特定的抑制剂，发现APG的作用与其PKC、CK2、PI3K、p38或ERK抑制活性无关。槲皮素 (10-40 mu M) 也是一种黄酮类化合物，也能抑制氯高铁血红素诱导的 HO-1 表达。此外，使用 HO-1-luc 转基因小鼠的体内研究表明，APG (50 mg/kg) 降低了氯化血红素诱导的 HO 活性和肝脏中 HO-1 蛋白的表达。这些结果表明，黄酮类化合物（例如 APG）可以减弱氯化血红素诱导的 HO-1 表达。 (c) 2005 Elsevier Inc. 保留所有权利。
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-I 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 NOS and COX-2, on HO-1 expression. Incubation of mouse embryonic fibroblasts with APG (5-40 mu l) 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 mu M), 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 favonoids, such as APG. (c) 2005 Elsevier Inc. All rights reserved.