Pan Yanchao, Zhang Hua, Zheng Yueting, Zhou Juanzuo, Yuan Jing, Yu Yang, Wang Jiangyun
Diagnosis and Treatment of Infectious Diseases Research Laboratory, Shenzhen Third People's Hospital , Shenzhen 518112, China.
Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences , 15 Datun Road, Chaoyang District, Beijing 100101, China.
Biochemistry. 2017 Dec 5;56(48):6325-6328. doi: 10.1021/acs.biochem.7b00859. Epub 2017 Nov 16.
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 HO reduction activity and a decreased cellular HO concentration. Knockdown of SIRT2 or Prx1 by RNA interference abrogates resveratrol's ability to reduce the HO 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 HO reducing activity. Thus, SIRT2 and Prx1 are targets for modulating intracellular redox status in the therapeutic strategies for the treatment of aging-related disorders.
白藜芦醇是一种有前景的化学制剂，可治疗多种与衰老相关的疾病并延长寿命。虽然活性氧无疑在衰老过程中发挥着普遍作用，且白藜芦醇已被证明是一种有效的抗氧化剂，但白藜芦醇对抗氧化应激的作用机制仍不清楚。在此我们表明，白藜芦醇激活SIRT2使Prx1去乙酰化，导致HO还原活性增加和细胞内HO浓度降低。通过RNA干扰敲低SIRT2或Prx1可消除白藜芦醇降低HepG2细胞中HO水平的能力。使用纯化的SIRT2和在第27位含有乙酰赖氨酸的Prx1突变体（Prx1-27AcK），我们表明白藜芦醇增强了SIRT2使Prx1-27AcK去乙酰化的活性，导致HO还原活性显著增加。因此，在治疗与衰老相关疾病的治疗策略中，SIRT2和Prx1是调节细胞内氧化还原状态的靶点。
