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sirtuin 1 in rat orthotopic liver transplantation:An I GL-1 preservation solution approach

World Journal of Gastroenterology 2015年第6期21卷 1765-1774页

作者： Eirini Pantazi Mohamed Amine Zaouali Mohamed Bejaoui Emma Folch-Puy Hassen Ben Abdennebi Ana Teresa Varela Anabela Pinto Rolo Carlos Marques Palmeira Joan Roselló-Catafau Experimental Hepatic Ischemia Reperfusion Unit Institute of Biomedical Research of Barcelona Faculty of Pharmacy Molecular Biology and Anthropology Applied to Development and Health Department of Life Sciences and Center for Neuroscience and Cell Biology University of Coimbra Department of Biology University of Aveiro

AIM:To investigate the possible involvement of sirtuin1(SIRT1)in rat orthotopic liver transplantation(OLT),when Institute Georges Lopez 1(IGL-1)preservation solution is enriched with trimetazidine(TMZ).METHODS:Male Sprague-Dawley rats were used as donors and *** were stored in IGL-1 preservation solution for 8h at 4℃,and then underwent OLT according to Kamada’s cuff technique without *** another group,livers were stored in IGL-1 preservation solution supplemented with TMZ,at10-6 mol/L,for 8 h at 4℃and then underwent *** were sacrificed 24 h after reperfusion,and liver and plasma samples were *** injury(transaminase levels),mitochondrial damage(glutamate dehydrogenase activity)oxidative stress(malondialdehyde levels),and nicotinamide adenine dinucleotide(NAD+),the cofactor necessary for SIRT1 activity,were determined by biochemical ***1 and its substrates(acFox O1,ac-p53),the precursor of NAD+,nicotinamide phosphoribosyltransferase(NAMPT),as well as the phosphorylation of adenosine monophosphate activated protein kinase(AMPK),p-m TOR,p-p70S6K(direct substrate of m TOR),autophagy parameters(beclin-1,LC3B)and MAP kinases(p-p38 and p-ERK)were determined by Western ***:Liver grafts preserved in IGL-1 solution enriched with TMZ presented reduced liver injury and mitochondrial damage compared with those preservedin IGL-1 solution *** addition,livers preserved in IGL-1+TMZ presented reduced levels of oxidative *** was consistent with enhanced SIRT1 protein expression and elevated SIRT1 activity,as indicated by decreased acetylation of p53 and Fox *** elevated SIRT1 activity in presence of TMZ can be attributed to the enhanced NAMPT protein and NAD+/NADH ***-regulation of SIRT1 was consistent with activation of AMPK and inhibition of phosphorylation of m TOR and its direct substrate(p-p70S6K).As a consequence,autophagy mediators(beclin-1 and LC3B)were ***,MAP kinases w

关键词： sirtuin 1 Ischemia-reperfusion injury Liver transp

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sirtuin 1 alleviates endoplasmic reticulum stress-mediated apoptosis of intestinal epithelial cells in ulcerative colitis

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World Journal of Gastroenterology 2019年第38期25卷 5800-5813页

作者： Meng-Ting Ren Meng-Li Gu Xin-Xin Zhou Mo-Sang Yu Hang-Hai Pan Feng Ji Chen-Yan Ding Department of Gastroenterology The First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou 310003Zhejiang ProvinceChina Department of Gastroenterology Ningbo First HospitalNingbo 315000Zhejiang ProvinceChina Department of Gastroenterology Zhejiang Provincial People's HospitalPeople's Hospital of Hangzhou Medical CollegeHangzhou 310014Zhejiang ProvinceChina Department of Emergency Medicine The First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou 310003Zhejiang ProvinceChina

BACKGROUND sirtuin 1(SIRT1)is a nicotinamide adenine dinucleotide(NAD+)-dependent protein deacetylase that is involved in various diseases,including cancers,metabolic diseases,and inflammation-associated ***,the role of SIRT1 in ulcerative colitis(UC)is still *** To investigate the role of SIRT1 in intestinal epithelial cells(IECs)in UC and further explore the underlying *** We developed a coculture model using macrophages and Caco-2 *** treatment with the SIRT1 activator SRT1720 or inhibitor nicotinamide(NAM),the expression of occludin and zona occludens 1(ZO-1)was assessed by Western blot *** V-APC/7-AAD assays were performed to evaluate Caco-2 *** sodium sulfate(DSS)-induced colitis mice were exposed to SRT1720 or NAM for 7 ***-mediated dUTP nick-end labeling(TUNEL)assays were conducted to assess apoptosis in colon *** expression levels of glucose-regulated protein 78(GRP78),CCAAT/enhancerbinding protein homologous protein(CHOP),caspase-12,caspase-9,and caspase-3 in Caco-2 cells and the colon tissues of treated mice were examined by quantitative real-time PCR and Western *** SRT1720 treatment increased the protein levels of occludin and ZO-1 and inhibited Caco-2 apoptosis,whereas NAM administration caused the opposite ***-induced colitis mice treated with SRT1720 had a lower disease activity index(P<0.01),histological score(P<0.001),inflammatory cytokine levels(P<0.01),and apoptotic cell rate(P<0.01),while exposure to NAM caused the opposite ***,SIRT1 activation reduced the expression levels of GRP78,CHOP,cleaved caspase-12,cleaved caspase-9,and cleaved caspase-3 in Caco-2 cells and the colon tissues of treated *** SIRT1 activation reduces apoptosis of IECs via the suppression of endoplasmic reticulum stress-mediated apoptosis-associated molecules CHOP and ***1 activation may be a potential therapeutic strategy for UC.

关键词： sirtuin 1 Endoplasmic reticulum stress Apoptosis Ulcerative colitis Intestinal barrier

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sirtuin Functions in the Brain:From Physiological to Pathological Aspects

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Journal of Shanghai Jiaotong university(Science) 2014年第6期19卷 651-662页

作者：邵家骧张婷婷刘腾远全亦周李凡刘杰杨霄谢谦夏伟梁 State Key Laboratory of Oncogenes and Related Genes Renji-Med X Clinical Stem Cell Research CenterRenji HospitalShanghai Jiaotong University School of Medicine School of Biomedical Engineering Shanghai Jiaotong University Med-X Research Institute Shanghai Jiaotong University

sirtuins are a family of nicotinamide adenine dinucleotide(NAD+) dependent deacetylases involved in multiple biological functions including metabolism, inflammation, stress resistance and aging. In mammals,there are seven members(Sirt1—Sirt7), with diversities in their subcellular localizations and enzymatic ***, we review the functions of sirtuins, with a focus on their roles in normal brain physiology such as neural development regulation, body homeostasis maintenance, and memory formation. We also discuss the role of sirtuins in a variety of brain diseases including stroke, Alzheimer's, Parkinson's, and motor neuron *** of the emerging functions of sirtuins in brain physiology and pathology, drugs targeting sirtuins may offer potential therapeutic values for brain disorders.

关键词： sirtuin neural development hypothalamic function stroke neurodegeneration

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Quercetin prevents spinal motor neuron degeneration induced by chronic excitotoxic stimulus by a sirtuin 1-dependent mechanism

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Translational Neurodegeneration 2017年第1期6卷 310-323页

作者： Rafael Lazo-Gomez Ricardo Tapia División de Neurociencias Instituto de Fisiología CelularUniversidad Nacional Autónoma de MéxicoCircuito exterior s/nCiudad UniversitariaCoyoacán04510 Ciudad de MéxicoMexico

Background:Excitotoxicity is a mechanism of foremost importance in the selective motor neuron degeneration characteristic of motor neuron *** therapeutic strategies are an unmet need for these ***,such as quercetin and resveratrol,are plant-derived compounds that activate sirtuins(SIRTs)and have shown promising results in some models of neuronal death,although their effects have been scarcely tested in models of motor neuron ***:In this work we investigated the effects of quercetin and resveratrol in an in vivo model of excitotoxic motor neuron death induced by the chronic infusion ofα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid(AMPA)into the rat spinal cord *** and resveratrol were co-infused with AMPA and motor behavior and muscle strength were assessed daily for up to ten ***,animals were fixed and lumbar spinal cord tissue was analyzed by histological and immunocytological ***:We found that the chronic infusion of AMPA[1 mM]caused a progressive motor neuron degeneration,accompanied by astrogliosis and microgliosis,and motor deficits and paralysis of the rear *** infusion ameliorated AMPA-induced paralysis,rescued motor neurons,and prevented both astrogliosis and microgliosis,and these protective effects were prevented by EX527,a very selective SIRT1 *** contrast,neither resveratrol nor EX527 alone improved motor behavior deficits or reduced motor neuron degeneration,albeit both reduced ***:These results suggest that quercetin exerts its beneficial effects through a SIRT1-mediated mechanism,and thus SIRT1 plays an important role in excitotoxic neurodegeneration and therefore its pharmacological modulation might provide opportunities for therapy in motor neuron disorders.

关键词： Motor neuron disorder Quercetin Resveratrol sirtuin Excitotoxicity

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sirtuin及其食源性激活剂对衰老相关疾病的调控作用研究进展

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中国食品学报 2023年第4期23卷 390-412页

作者：张涵尹淑涛扈洪波赵冲中国农业大学食品科学与营养工程学院北京100083

sirtuin是NAD+依赖性去乙酰化酶,可以从组蛋白和其它底物蛋白赖氨酸的ε-氨基中脱去乙酰基和其它酰基。研究表明,sirtuin是热量限制调控疾病的重要靶点,可以作为一种信号转导分子,参与调控代谢综合征、癌症、心血管疾病和神经退行性疾... 详细信息

sirtuin是NAD+依赖性去乙酰化酶,可以从组蛋白和其它底物蛋白赖氨酸的ε-氨基中脱去乙酰基和其它酰基。研究表明,sirtuin是热量限制调控疾病的重要靶点,可以作为一种信号转导分子,参与调控代谢综合征、癌症、心血管疾病和神经退行性疾病等多种衰老相关疾病的发生和发展。近年来,多项研究证据表明,多种化合物通过激活sirtuin,模拟热量限制预防和调控疾病。为更好地了解sirtuin在这些疾病中的作用机制,进而从食物中筛选出以sirtuin为靶点的有效活性成分,本文聚焦sirtuin调控的特定靶点和信号通路的最新研究进展,概述食源性的sirtuin激活剂在疾病预防及调控中的作用机制。

关键词： sirtuin 赖氨酸去乙酰酶衰老相关疾病食源性激活剂

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sirtuin3减少心肌细胞钙超载时细胞色素C的释放并抑制细胞凋亡

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细胞与分子免疫学杂志 2015年第8期31卷 1031-1035页

作者：叶璐杨双强重庆医科大学附属第一医院胸心外科重庆400016

目的研究sirtuin 3在心肌细胞钙超载时对细胞色素C(Cyt C)释放和caspase-3激活的影响。方法将培养的H9c2心肌细胞随机分为4组,即对照组、sirtuin 3组、离子霉素组(ionomycin组)和离子霉素联合sirtuin 3组(ionomycin联合sirtuin 3组)。采... 详细信息

目的研究sirtuin 3在心肌细胞钙超载时对细胞色素C(Cyt C)释放和caspase-3激活的影响。方法将培养的H9c2心肌细胞随机分为4组,即对照组、sirtuin 3组、离子霉素组(ionomycin组)和离子霉素联合sirtuin 3组(ionomycin联合sirtuin 3组)。采用ionomycin诱导法构建心肌细胞钙超载模型,Western blot法检测心肌细胞线粒体及胞质细胞色素C(Cyt C)和caspase-3的水平,分光光度法检测caspase-3的活性,AnnexinⅤ-FITC/PI双染色结合流式细胞术检测H9c2心肌细胞的凋亡比率。结果成功构建钙超载模型。Western blot结果显示Cyt C在线粒体中的水平ionomycin组明显低于对照组,ionomycin联合sirtuin 3组明显高于ionomycin组,Cyt C在胞质中的水平相反;Ionomycin组caspase-3的水平明显高于对照组,ionomycin联合sirtuin 3组caspase-3的水平明显低于ionomycin组。分光光度法结果显示caspase-3的活性ionomycin组明显高于对照组,ionomycin联合sirtuin 3组明显低于ionomycin组。双染色结合流式细胞术结果显示ionomycin组的凋亡比率明显高于对照组,ionomycin联合sirtuin 3组的凋亡比率明显低于ionomycin组。结论心肌细胞钙超载时,sirtuin 3通过减少Cyt C释放和caspase-3的激活,抑制细胞凋亡。

关键词： sirtuin 3 心肌保护 mPTP 钙超载

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去乙酰化酶sirtuin与衰老的研究进展

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生物化学与生物物理进展 2010年第12期37卷 1271-1277页

作者：彭琪陈维春刘新光广东医学院衰老研究所东莞523808 广东医学院检验医学研究所东莞523808 广东医学院生物化学与分子生物学研究所湛江524023

sirtuin蛋白是一组具有NAD+依赖性的组蛋白去乙酰基转移酶,该家族成员具有高度保守的催化结构域,可以通过对多种底物进行去乙酰化作用,从而在机体内参与一系列的生物学活动,包括维持细胞抗胁迫能力和基因组稳定性以及参与能量代谢等.Sir... 详细信息

sirtuin蛋白是一组具有NAD+依赖性的组蛋白去乙酰基转移酶,该家族成员具有高度保守的催化结构域,可以通过对多种底物进行去乙酰化作用,从而在机体内参与一系列的生物学活动,包括维持细胞抗胁迫能力和基因组稳定性以及参与能量代谢等.Sir2参与了酵母的交配型基因、端粒和rDNA重复序列的沉默以及细胞寿命等生理功能.在哺乳动物中,SIRT1是该家族中目前研究最为广泛且较为透彻的成员,而SIRT6的功能研究成为近年来继SIRT1后的又一新热点.综述了sirtuin蛋白的结构及其与衰老关系的研究进展.

关键词： sirtuin 衰老 NAD 去乙酰化酶

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Inhibition of sirtuin 2 exerts neuroprotection in aging rats with increased neonatal iron intake

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Neural Regeneration Research 2014年第21期9卷 1917-1922页

作者： Xijin Wang Meihua Wang Liu Yang Jie Bai Zhiqiang Yan Yuhong Zhang Zhenguo Liu Department of Neurology Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai Laboratory Animal Center Chinese Academy of Sciences Department of Neurology Shanghai Tenth People’s HospitalTongji University

Impaired iron homeostasis may cause damage to dopaminergic neurons and is critically involved in the pathogenesis of Parkinson’s disease. At present, very little is understood about the effect of neonatal iron intake on behavior in aging animals. Therefore, we hypothesized that increased neonatal iron intake would result in signiifcant behavior abnormalities and striatal dopamine depletion during aging, and sirtuin 2 contributes to the age-related neurotoxicity. In the present study, we observed that neonatal iron intake （120 μg/g per day） during postnatal days 10–17 resulted in significant behavior abnormalities and striatal dopamine depletion in aging rats. Furthermore, after AK-7 （a selective sirtuin 2 inhibitor） was injected into the substantia nigra at postnatal 540 days and 570 days （5 μg/side per day）, striatal dopamine depletion was signiifcant-ly diminished and behavior abnormality was improved in aging rats with neonatal iron intake. Experimental ifndings suggest that increased neonatal iron intake may result in Parkinson’s dis-ease-like neurochemical and behavioral deifcits with aging, and inhibition of sirtuin 2 expression may be a neuroprotective measure in Parkinson’s disease.

关键词： nerve regeneration Parkinson’s disease iron homeostasis disruption aging dopamine corpus striatum neurotoxicity sirtuin AK-7 NSFC grants neural regeneration

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sirtuin-1 mediates the obesity induced risk of common degenerative diseases: Alzheimer’s disease, coronary artery disease and type 2 diabetes

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Health 2012年第12期4卷 1448-1456页

作者： Ian James Martins Andrea. C. Wilson Wei Ling Florence Lim Simon. M. Laws Stephanie. J. Fuller Ralph Nigel Martins Centre of Excellence in Alzheimer’s Disease Research and Care School of Medical Sciences Edith Cowan University Perth Australia McCusker Alzheimer’s Research Foundation Hollywood Medical Centre Perth Australia School of Psychiatry and Clinical Neurosciences The University of Western Australia Perth Australia

Obesity, especially at mid-life, is a major risk factor for atherosclerosis, insulin resistance and the metabolic syndrome, which in turn contribute to coronary artery disease (CAD), Type 2 diabetes and Alzheimer’s disease (AD). The rise in overweight and obesity in all societies is prompting intense research into the causes and effects of the condition. Obesity disrupts many body systems including glucose and lipid metabolism, circadian rhythms and liver function. It also causes or increases inflammation and oxidative stress. Within cells, the endoplasmic reticulum (ER) appears to be particularly susceptible to such metabolic disruption. sirtuin 1?(Sirt1) and leptin have received attention recently as they are central regulatory factors for the body’s metabolic pathways which interact at particular levels, for example lipid and Abeta metabolism. This mini-review discusses recent findings concerning obesity, lipid metabolism and the role of sirtuin 1 and how all influence the ER. A greater understanding of obesity and its effects on metabolic control systems of the body are required, to develop pharmacological, dietary and lifestyle changes that will reduce the incidence of CAD, Type 2 diabetes and AD.

关键词： Obesity sirtuin 1 Alzheimer’s Disease Cardiovascular Disease Diabetes

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sirtuin家族调控骨关节炎软骨细胞的作用机制研究进展

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中国骨质疏松杂志 2024年第4期30卷 600-605页

作者：何帮靖周明旺王晓萍张朋威张纪平张亚衡甘肃中医药大学甘肃兰州730000 甘肃省中医院甘肃兰州730050

骨关节炎(osteoarthritis,OA)是常见的慢性退行性疾病,以关节软骨的进行性破坏为主要病理特征。研究证实软骨组织中软骨细胞功能障碍是OA进展的关键因素,包括能量代谢、生物钟、自噬和凋亡的异常激活及衰老软骨细胞的增加等生物过程。... 详细信息

骨关节炎(osteoarthritis,OA)是常见的慢性退行性疾病,以关节软骨的进行性破坏为主要病理特征。研究证实软骨组织中软骨细胞功能障碍是OA进展的关键因素,包括能量代谢、生物钟、自噬和凋亡的异常激活及衰老软骨细胞的增加等生物过程。沉默信息调节因子(sirtuin,SIRT)是依赖于烟酰胺烟嘌呤二核苷酸的去乙酰化酶家族,通过参与并调节软骨细胞功能过程中的蛋白质去乙酰化,从而延缓OA进展。依据文献报道,本文将围绕SIRT家族成员对OA软骨细胞功能的调控作用机制进行概述,旨在对SIRT家族在OA软骨细胞的作用机制有进一步认识和为今后靶向治疗OA提供思路。

关键词：骨关节炎软骨细胞 sirtuin

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