Hydrogen peroxide mediates EGCG-induced antioxidant protection in human keratinocytes

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• 作者：Leonilla Elbling ; Irene Herbacek ; Rosa-Maria Weiss ; Christian Jantschitsch ; Michael Micksche ; Christopher Gerner ; Heinrich Pangratz ; Michael Grusch ; Siegfried Knasmü ; ller ; Walter Berger
• 关键词：Green tea ; Polyphenol ; Hydrogen peroxide ; EGCG ; Protection ; DNA damage ; Free radicals
• 刊名：Free Radical Biology and Medicine
• 出版年：2010
• 出版时间：15 November 2010
• 年：2010
• 卷：49
• 期：9
• 页码：1444-1452
• 全文大小：986 K

文摘

The beneficial health effects of (−)-epigallocatechin-3-gallate (EGCG), the main catechin of green tea, have been attributed to complex interactions with a focus on antioxidative properties. Susceptibility to autoxidation and production of cytotoxic reactive oxygen species (ROS), mostly H₂O₂, have been suggested to occur in vitro but also in vivo. In this study, we address whether autoxidation-derived H₂O₂ may be involved in the cytoprotective effects of EGCG. To that end we investigated keratinocyte-derived HaCat and HL-60 promyelocytic leukemia cells with significantly different sensitivities to H₂O₂ (IC₅₀ 117.3 versus 58.3 μM, respectively) and EGCG (134.1 versus 84.1 μM). HaCat cells significantly resisted cytotoxicity and DNA damage based on enhanced H₂O₂ clearance, improved DNA repair, and reduced intracellular ROS generation. Cumulative versus bolus EGCG and H₂O₂ treatment and H₂O₂ pretreatment before subsequent high-dose EGCG and vice versa significantly reduced DNA damage and cytotoxicity in HaCat cells only. Addition of catalase abolished the protective activities of low-dose H₂O₂ and EGCG. In summary, our data suggest that autoxidative generation of low-dose H₂O₂ is a significant player in the cell-type-specific cytoprotection mediated by EGCG and support the hypothesis that regular green tea consumption can contribute as a pro-oxidant to increased resistance against high-dose oxidative stressors.