SIRT3
烟酰胺单核苷酸
氧化应激
平衡
化学
肝损伤
SOD2
下调和上调
生物化学
内分泌学
细胞生物学
乙酰化
NAD+激酶
生物
超氧化物歧化酶
烟酰胺腺嘌呤二核苷酸
锡尔图因
酶
基因
作者
Chengting Luo,Wenxi Ding,Changmei Yang,Wenhao Zhang,Xiaohui Liu,Haiteng Deng
标识
DOI:10.1021/acs.jproteome.2c00167
摘要
Altered adaptive homeostasis contributes to aging and lifespan regulation. In the present study, to characterize the mechanism of aging in mouse liver, we performed quantitative proteomics and found that the most upregulated proteins were related to the oxidation-reduction process. Further analysis revealed that malondialdehyde (MDA) and protein carbonyl (PCO) levels were increased, while nuclear Nrf2 and downstream genes were significantly increased, indicating that oxidative stress induced Nrf2 activation in aged mouse liver. Importantly, nicotinamide mononucleotide (NMN) administration decreased the oxidative stress and the nuclear Nrf2 and Nrf2 downstream gene levels. Indeed, aged mice treated with NMN improved stress resistance against acetaminophen (APAP)-induced liver injury, indicating that NMN restored Nrf2-mediated adaptive homeostasis. Further studies found that NMN increased Sirt3 activities to deacetylate age-associated acetylation at K68 and K122 in Sod2, while its effects on nuclear Nrf2 levels were diminished in Sirt3-deficient mice, suggesting that NMN-enhanced adaptive homeostasis was Sirt3-dependent. Taken together, we demonstrated that Nrf2-regulated adaptive homeostasis was decreased in aged mouse liver and NMN supplementation restored liver redox homeostasis via the Sirt3-Nrf2 axis and protected aged liver from oxidative stress-induced injury.
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