Curcumin induces heme oxygenase-1 in normal human skin fibroblasts through redox signaling: Relevance for anti-aging intervention
Curcumin induces heme oxygenase-1 in normal human skin fibroblasts through redox signaling: Relevance for anti-aging intervention
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DOI：
10.1002/mnfr.201000221
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发表时间：
2011-03-01
影响因子：
5.2
通讯作者：
Rattan, Suresh I. S.
中科院分区：
文献类型：
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作者：
Lima, Cristovao F.;Pereira-Wilson, Cristina;Rattan, Suresh I. S.
适用范围：姜黄素是香料姜黄的一种成分，作为温和压力的诱导物，测试其潜在的激素抗衰老作用。方法和结果：用低剂量姜黄素处理的早期传代年轻人皮肤成纤维细胞（低于20 μ M）表现出时间和浓度依赖性的血红素加氧酶-1（HO-1）诱导，随后谷胱甘肽-S-转移酶活性、GSH水平和GSH/GSSG比值代偿性增加。这些作用之前诱导氧化应激（活性氧和DNA损伤水平增加）和细胞GSH氧化还原状态受损。姜黄素还诱导核因子-红细胞-2相关因子2在细胞核中的积累。抗氧化剂N-乙酰半胱氨酸的使用阻止了姜黄素对HO-1的诱导。药理学抑制磷脂酰肌醇3-激酶，而不是其他激酶，显着防止姜黄素诱导的HO-1水平，这是证实了由姜黄素诱导的磷酸化Akt水平。晚代衰老细胞已经具有较高的HO-1水平，并且姜黄素对HO-1的进一步诱导受到相当大的损害。姜黄素在人体细胞中诱导的应激反应导致保护性激素效应，以进一步氧化challenge.Conclusion：姜黄素诱导细胞的应激反应，在正常人皮肤成纤维细胞通过磷脂酰肌醇3-激酶/Akt途径和氧化还原信号，支持姜黄素诱导的激素刺激细胞的抗氧化防御系统可以是一个有用的抗衰老干预的方法。
Scope: Curcumin, a component of the spice turmeric, was tested for its potential hormetic anti-aging effects as an inducer of mild stress.Methods and results: Early passage young human skin fibroblasts treated with low doses of curcumin (below 20 mu M) showed a time-and concentration-dependent induction of heme oxygenase-1 (HO-1), followed by compensatory increase in glutathione-S-transferase activity, GSH levels and GSH/GSSG ratio. These effects were preceded by induction of oxidative stress (increased levels of reactive oxygen species and DNA damage) and impairment of cells' GSH redox state. Curcumin also induced nuclear factor-erythroid-2-related factor 2 accumulation in the nuclei. The use of the antioxidant N-acetyl cysteine prevented the induction of HO-1 by curcumin. Pharmacological inhibition of phosphatidylinositol 3-kinase, but not other kinases, significantly prevented curcumin-induced HO-1 levels, which was corroborated by the induction of phospho-Akt levels by curcumin. Late passage senescent cells already had higher HO-1 levels, and further induction of HO-1 by curcumin was considerably impaired. The induction of stress responses by curcumin in human cells led to protective hormetic effects to further oxidant challenge.Conclusion: Curcumin induces cellular stress responses in normal human skin fibroblasts through phosphatidylinositol 3-kinase/Akt pathway and redox signaling, supporting the view that curcumin-induced hormetic stimulation of cellular antioxidant defenses can be a useful approach toward anti-aging intervention.