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The NAD(+)-dependent deacetylase, Bifidobacterium longum Sir2 in response to oxidative stress by deacetylating SigH (sigma(H)) and FOXO3a in Bifidobacterium longum and HEK293T cell respectively

文献类型： 外文期刊

作者： Guo, Qing 1 ; Li, Shiyu 2 ; Xie, Yajie 1 ; Zhang, Qian 1 ; Liu, Mengge 1 ; Xu, Zhenrui 1 ; Sun, Hanxiao 1 ; Yang, Yan 3 ;

作者机构： 1.Jinan Univ, Coll Pharm, Inst Genom Med, Guangzhou 510632, Guangdong, Peoples R China

2.Southern Med Univ, Inst Genet Engn, Guangzhou 510515, Guangdong, Peoples R China

3.Henan Acad Agr Sci, Res Ctr Agr & Sideline Prod Proc, Zhengzhou 450002, Peoples R China

关键词： Bifidobacterium longum;Lactobacillus acidophilus;Sir2;Oxidative stress;sigH;FOXO3a

期刊名称：FREE RADICAL BIOLOGY AND MEDICINE （ 影响因子：7.376； 五年影响因子：7.934 ）

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收录情况： SCI

摘要： Silent information regulator 2 (Sir2) enzymes which catalyze NAD+-dependent protein/histone deacetylation. The mammalian sirtuin family SIRT1, SIRT2, SIRT3 and SIRT6 can regulate oxidative stress. The probiotics (Bifidobacterium longum(B. longum) and Lactobacillus acidophilus(L. acidophilus)) have Sir2 gene family and have antioxidant activity in human body. it remains unknown whether probiotics Sir2 has a direct role in regulating oxidative stress. To this end, we knockout BL-sir2(sir2 B. longum) and LA-sir2(sir2 L. acidophilus) in low oxygen level. The antioxidant activities of two sir2 deficient strains was decreased, while when reintroduction of BL-sir2 and LA-sir2, the antioxidant activities were recoveried. In order to understand the regulation mechanism of probiotics Sir2 oxidation response. Then, we screened 65 acetylated protein, and found that SigH (sigma(H)) was a substrate of BL-Sir2. In addition, the acetylation level of sigma(H) decreased with the increase of BL-Sir2 level in B. longum. Thus, BL-Sir2 deacetylated sigma(H) in response to oxidative stress. Next, we transfected BL-Sir2 into H2O2-induced oxidative damage of 293 T cells, BL-Sir2 increased the activity of manganese superoxide dismutase (MnSOD/SOD2) and catalase (CAT) and reduced reactive oxygen species(ROS). Then, we analyzed the differential gene by RNA sequencing and Gene ontology (GO) and found that BL-Sir2 regulated forkhead transcription factor (FOXO3a) mediated antioxidant genes in overexpressed BL-Sir2 HEK293T cells. Our study is the first to link probiotics Sir2 with oxidative stress and uncover the antioxidant mechanism of BL-Sir2 in B. longum itself and human body.

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