Nicotinamide riboside relieves the severity of experimental necrotizing enterocolitis by regulating endothelial function via eNOS deacetylation

作者全名："Zhang, Xiao; Tian, Bing; Deng, Qin; Cao, Jian; Ding, Xionghui; Liu, Qingshuang; Zhang, Yunfei; Ye, Cuilian; Deng, Chun; Qiu, Lin; Guo, Chunbao"

作者地址："[Zhang, Xiao; Deng, Qin; Cao, Jian; Liu, Qingshuang; Guo, Chunbao] Chongqing Med Univ, Dept Gen & Neonatal Surg, Childrens Hosp, Chongqing, Peoples R China; [Zhang, Xiao; Ding, Xionghui; Zhang, Yunfei; Qiu, Lin; Guo, Chunbao] Chongqing Med Univ, Dept Burn, Childrens Hosp, Chongqing, Peoples R China; [Tian, Bing; Deng, Chun] Chongqing Med Univ, Yongchuan Hosp, Dept Pediat, Chongqing 400054, Peoples R China; [Deng, Qin; Qiu, Lin] Chongqing Med Univ, Yongchuan Hosp, Dept Clin Nutr, Chongqing 400054, Peoples R China; [Ye, Cuilian; Qiu, Lin] Chongqing Univ Technol, Sch Pharm & Bioengn, Chongqing 400054, Peoples R China; [Zhang, Xiao; Tian, Bing; Deng, Qin; Cao, Jian; Ding, Xionghui; Liu, Qingshuang; Zhang, Yunfei; Deng, Chun; Qiu, Lin; Guo, Chunbao] Natl Clin Res Ctr Child Hlth & Disorders, Chongqing, Peoples R China; [Zhang, Xiao; Tian, Bing; Deng, Qin; Cao, Jian; Ding, Xionghui; Liu, Qingshuang; Zhang, Yunfei; Deng, Chun; Qiu, Lin; Guo, Chunbao] Minist Educ, Key Lab Childrens Dev & Disorders, Chongqing, Peoples R China; [Zhang, Xiao; Tian, Bing; Deng, Qin; Cao, Jian; Ding, Xionghui; Liu, Qingshuang; Zhang, Yunfei; Deng, Chun] Natl Int Sci & Technol Cooperat Base Dev & Crit Di, Chongqing, Peoples R China; [Zhang, Xiao; Tian, Bing; Deng, Qin; Cao, Jian; Ding, Xionghui; Liu, Qingshuang; Zhang, Yunfei; Deng, Chun; Guo, Chunbao] Key Lab Pediat Chongqing, Chongqing 400014, Peoples R China; [Guo, Chunbao] Chongqing Med Univ, Dept Gen & Neonatal Surg, Childrens Hosp, 136 Zhongshan 2nd Rd, Chongqing 400014, Peoples R China"

通信作者："Qiu, L; Guo, CB (通讯作者)，Chongqing Med Univ, Dept Burn, Childrens Hosp, Chongqing, Peoples R China.; Qiu, L; Guo, CB (通讯作者)，Minist Educ, Key Lab Childrens Dev & Disorders, Chongqing, Peoples R China.; Guo, CB (通讯作者)，Chongqing Med Univ, Dept Gen & Neonatal Surg, Childrens Hosp, 136 Zhongshan 2nd Rd, Chongqing 400014, Peoples R China."

来源：FREE RADICAL BIOLOGY AND MEDICINE

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000795121600002

JCR分区：Q1

影响因子：7.4

年份：2022

卷号：184

期号：　

开始页：218

结束页：229

文献类型：Article

关键词：Necrotizing enterocolitis; Oxidative stress; SIRT1; Nicotinamide riboside; Endothelial nitric oxide synthase; Intestinal microcirculation

摘要："Background: Nicotinamide adenine dinucleotide (NAD+) is involved in regulating oxidative stress. Although NAD+ is associated with various health issues, its role in the intestinal microcirculation in necrotizing enterocolitis (NEC) remains to be confirmed. In the current study, we explored whether nicotinamide riboside (NR), a natural NAD + precursor, ameliorates the severity of NEC through endothelial nitric oxide synthase(eNOS) signaling.Methods: A mouse experimental NEC model was induced by formula gavage and hypoxia in full-term mouse pups. Intestinal endothelial cells (MIMECs) were isolated and subjected to stress using tumor necrosis factor (TNF)-alpha. NR was administered to assess the intestinal microcirculation and lipid peroxidation levels and to explore the involved signaling pathways.Results: NAD + levels were reduced after induction of NEC stress, which was associated with intestinal injury. NR administration promoted NAD + levels, attenuated oxidative stress and relieved the symptoms of experimental NEC, which were relevant to increased intestinal microcirculatory perfusion through the sirtuin (SIRT) 1 pathway in experimental NEC mice. However, this improvement was not found in eNOS-knockout mice. Consistently, MIMECs exposed to TNF alpha showed decreased SIRT1 activity associated with increased eNOS acetylation, which could bring about endothelial dysfunction due to limited nitric oxide production. NR administration increased the NAD + content and repressed the production of reactive oxygen species (ROS) in MIMECs under TNF alpha stress. NR also promoted SIRT1 activity and accordingly suppressed the eNOS acetylation levels under TNF alpha stress.Conclusion: The current data indicate that NR administration improves the survival of experimental NEC mice via SIRT1-associated eNOS acetylation/deacetylation modulation, which is implicated in endothelial dysfunction. Although NR is commonly found in the human diet, it may also be a promising strategy for NEC treatment because of its pathogenic association with NEC."

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