The Natural Polyphenol Epigallocatechin Gallate Protects Intervertebral Disc Cells from Oxidative Stress.
The Natural Polyphenol Epigallocatechin Gallate Protects Intervertebral Disc Cells from Oxidative Stress.
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DOI：
10.1155/2016/7031397
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发表时间：
2016
影响因子：
--
通讯作者：
Wuertz-Kozak K
中科院分区：
文献类型：
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作者：
Krupkova O;Handa J;Hlavna M;Klasen J;Ospelt C;Ferguson SJ;Wuertz-Kozak K
氧化应激相关的表型变化和活细胞数量的减少是椎间盘退变的关键因素。多酚表没食子儿茶素 3-没食子酸酯 (EGCG) 可通过减少炎症、分解代谢和疼痛来干扰椎间盘退变。在这项研究中，我们假设 EGCG 还可以防止氧化应激引起的衰老和/或细胞死亡。用 H2O2 在原代人椎间盘细胞中诱导亚致死和致死氧化应激（总计 n = 36）。在亚致死条件下，测试了 EGCG 对 p53-p21 激活、增殖能力和衰老相关 β-半乳糖苷酶积累的影响。此外，还分析了致命氧化应激中 EGCG 对线粒体去极化和细胞活力的影响。应用抑制剂 LY249002 研究 PI3K/Akt 通路。 EGCG抑制衰老相关的β-半乳糖苷酶的积累，但不影响增殖能力的丧失，表明EGCG没有完全中和外源自由基。此外，EGCG 通过激活促存活 PI3K/Akt 和保护线粒体，增加了 IVD 细胞在致命氧化应激下的存活率。我们证明，EGCG 不仅可以抑制炎症，还可以增强氧化应激下椎间盘细胞的存活率，这使其成为开发针对椎间盘退变的新型疗法的合适候选者。
Oxidative stress-related phenotypic changes and a decline in the number of viable cells are crucial contributors to intervertebral disc degeneration. The polyphenol epigallocatechin 3-gallate (EGCG) can interfere with painful disc degeneration by reducing inflammation, catabolism, and pain. In this study, we hypothesized that EGCG furthermore protects against senescence and/or cell death, induced by oxidative stress. Sublethal and lethal oxidative stress were induced in primary human intervertebral disc cells with H2O2 (total n = 36). Under sublethal conditions, the effects of EGCG on p53-p21 activation, proliferative capacity, and accumulation of senescence-associated β-galactosidase were tested. Further, the effects of EGCG on mitochondria depolarization and cell viability were analyzed in lethal oxidative stress. The inhibitor LY249002 was applied to investigate the PI3K/Akt pathway. EGCG inhibited accumulation of senescence-associated β-galactosidase but did not affect the loss of proliferative capacity, suggesting that EGCG did not fully neutralize exogenous radicals. Furthermore, EGCG increased the survival of IVD cells in lethal oxidative stress via activation of prosurvival PI3K/Akt and protection of mitochondria. We demonstrated that EGCG not only inhibits inflammation but also can enhance the survival of disc cells in oxidative stress, which makes it a suitable candidate for the development of novel therapies targeting disc degeneration.