Motterlini R, Foresti R, Bassi R, Green C J
Vascular Biology Unit, Department of Surgical Research, Northwick Park Institute for Medical Research, Harrow, UK.
Free Radic Biol Med. 2000 Apr 15;28(8):1303-12. doi: 10.1016/s0891-5849(00)00294-x.
Curcumin, a widely used spice and coloring agent in food, has been shown to possess potent antioxidant, antitumor promoting and anti-inflammatory properties in vitro and in vivo. The mechanism(s) of such pleiotropic action by this yellow pigment is unknown; whether induction of distinct antioxidant genes contributes to the beneficial activities mediated by curcumin remains to be investigated. In the present study we examined the effect of curcumin on endothelial heme oxygenase-1 (HO-1 or HSP32), an inducible stress protein that degrades heme to the vasoactive molecule carbon monoxide and the antioxidant biliverdin. Exposure of bovine aortic endothelial cells to curcumin (5-15 microM) resulted in both a concentration- and time-dependent increase in HO-1 mRNA, protein expression and heme oxygenase activity. Hypoxia (18 h) also caused a significant (P < 0.05) increase in heme oxygenase activity which was markedly potentiated by the presence of low concentrations of curcumin (5 microM). Interestingly, prolonged incubation (18 h) with curcumin in normoxic or hypoxic conditions resulted in enhanced cellular resistance to oxidative damage; this cytoprotective effect was considerably attenuated by tin protoporphyrin IX, an inhibitor of heme oxygenase activity. In contrast, exposure of cells to curcumin for a period of time insufficient to up-regulate HO-1 (1.5 h) did not prevent oxidant-mediated injury. These data indicate that curcumin is a potent inducer of HO-1 in vascular endothelial cells and that increased heme oxygenase activity is an important component in curcumin-mediated cytoprotection against oxidative stress.
姜黄素是一种在食品中广泛使用的香料和色素，已被证明在体外和体内均具有强大的抗氧化、抗肿瘤促进和抗炎特性。这种黄色色素产生这种多效作用的机制尚不清楚；姜黄素介导的有益活性是否由诱导不同的抗氧化基因所致仍有待研究。在本研究中，我们检测了姜黄素对内皮细胞血红素加氧酶-1（HO-1或HSP32）的影响，HO-1是一种可诱导的应激蛋白，可将血红素降解为血管活性分子一氧化碳和抗氧化剂胆绿素。将牛主动脉内皮细胞暴露于姜黄素（5-15微摩尔）会导致HO-1信使核糖核酸、蛋白表达和血红素加氧酶活性呈浓度和时间依赖性增加。缺氧（18小时）也会导致血红素加氧酶活性显著（P<0.05）增加，低浓度姜黄素（5微摩尔）的存在可明显增强这种增加。有趣的是，在常氧或缺氧条件下用姜黄素长时间孵育（18小时）会增强细胞对氧化损伤的抵抗力；血红素加氧酶活性抑制剂锡原卟啉IX可显著减弱这种细胞保护作用。相比之下，将细胞暴露于姜黄素一段不足以上调HO-1的时间（1.5小时）并不能预防氧化剂介导的损伤。这些数据表明，姜黄素是血管内皮细胞中HO-1的有效诱导剂，血红素加氧酶活性增加是姜黄素介导的针对氧化应激的细胞保护作用的重要组成部分。
