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飞燕草素-3-O-半乳糖苷通过上调血红素加氧酶-1 和热休克蛋白 70 保护小鼠肝细胞免受 (-)-表没食子儿茶素-3-没食子酸酯诱导的细胞毒性。

Delphinidin-3-O-galactoside protects mouse hepatocytes from (-)-epigallocatechin-3-gallate-induced cytotoxicity via up-regulation of heme oxygenase-1 and heat shock protein 70.

机构信息

Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.

出版信息

Nutr Res. 2012 May;32(5):357-64. doi: 10.1016/j.nutres.2012.04.001. Epub 2012 May 4.

DOI:10.1016/j.nutres.2012.04.001
PMID:22652375
Abstract

Delphinidin-3-O-galactoside (D3G) is a water-soluble anthocyanin with antioxidant activity. (-)-Epigallocatechin-3-gallate (EGCG) is also known as a powerful antioxidant but concomitantly possesses a prooxidative property. We hypothesized that D3G is capable of protecting the EGCG-induced cytotoxicity and endoplasmic reticulum (ER) stress via inducing self-protective proteins and antioxidant enzymes. (-)-Epigallocatechin-3-gallate (200-500 μM) dose dependently decreased the viability of hepa1c1c-7 mouse hepatocytes, whereas D3G (50-500 μM) did not change it. Pretreatment with D3G significantly suppressed EGCG-induced cytotoxicity in a time-dependent manner (0, 6, and 24 hours). (-)-Epigallocatechin-3-gallate drastically decreased heme oxygenase-1 and heat shock protein 70 messenger RNA (mRNA) levels, whereas, pretreatment with D3G markedly attenuated their down-regulations. Delphinidin-3-O-galactoside remarkably decreased EGCG-induced ER stress responses such as C/EBP-homologus protein mRNA expression and X-box-binding protein-1 mRNA splicing. Taken together, our data suggest that D3G is capable of masking the EGCG-induced cytotoxicity and ER stress, presumably through up-regulation of antioxidant enzymes and heat shock proteins.

摘要

矢车菊素-3-O-半乳糖苷(D3G)是一种具有抗氧化活性的水溶性花色苷。(-)-表没食子儿茶素-3-没食子酸酯(EGCG)也被认为是一种强大的抗氧化剂,但同时具有促氧化特性。我们假设 D3G 能够通过诱导自我保护蛋白和抗氧化酶来保护 EGCG 诱导的细胞毒性和内质网(ER)应激。(-)-表没食子儿茶素-3-没食子酸酯(200-500 μM)剂量依赖性地降低了 hepa1c1c-7 小鼠肝细胞的活力,而 D3G(50-500 μM)则没有改变。D3G 预处理以时间依赖性方式显著抑制 EGCG 诱导的细胞毒性(0、6 和 24 小时)。(-)-表没食子儿茶素-3-没食子酸酯明显降低血红素加氧酶-1 和热休克蛋白 70 信使 RNA(mRNA)水平,而 D3G 预处理则明显减弱了它们的下调。D3G 显著降低 EGCG 诱导的 ER 应激反应,如 C/EBP 同源蛋白 mRNA 表达和 X 框结合蛋白-1 mRNA 剪接。总之,我们的数据表明,D3G 能够掩盖 EGCG 诱导的细胞毒性和 ER 应激,可能是通过上调抗氧化酶和热休克蛋白。

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