Resveratrol is a promising chemical agent that treats multiple aging-related diseases and improves life span. While reactive oxygen species undoubtedly play ubiquitous roles in the aging process and resveratrol has been shown to be an effective antioxidant, the mechanism through which resveratrol acts against oxidative stress remains unknown. Here we show that resveratrol activates SIRT2 to deacetylate Prx1, leading to an increased H₂O₂ reduction activity and a decreased cellular H₂O₂ concentration. Knockdown of SIRT2 or Prx1 by RNA interference abrogates resveratrol’s ability to reduce the H₂O₂ level in HepG2 cells. Using purified SIRT2 and a Prx1 mutant harboring acetyllysine at position 27 (Prx1–27AcK), we show that resveratrol enhances SIRT2’s activity to deacetylate Prx1–27AcK, resulting in a significantly increased H₂O₂ reducing activity. Thus, SIRT2 and Prx1 are targets for modulating intracellular redox status in the therapeutic strategies for the treatment of aging-related disorders.

中文翻译：

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白藜芦醇通过激活SIRT2使Prx1脱乙酰基而发挥抗氧化作用

白藜芦醇是一种有前途的化学药物，可治疗多种与衰老有关的疾病并延长寿命。尽管活性氧无疑在衰老过程中起普遍作用，并且白藜芦醇已被证明是一种有效的抗氧化剂，但白藜芦醇通过其抗氧化应激的机理仍然未知。在这里，我们显示白藜芦醇激活SIRT2以使Prx1脱乙酰，从而导致增加的H ₂ O ₂还原活性和降低的细胞H ₂ O ₂浓度。RNA干扰抑制SIRT2或Prx1消除白藜芦醇减少H ₂ O ₂的能力HepG2细胞中的水平。使用纯化的SIRT2和在位置27（Prx1–27AcK）上带有乙酰赖氨酸的Prx1突变体，我们显示白藜芦醇可增强SIRT2的去乙酰化Prx1–27AcK的活性，从而显着增加H ₂ O _2的还原活性。因此，SIRT2和Prx1是调节衰老相关疾病的治疗策略中细胞内氧化还原状态的靶标。