检索结果-南通市图书馆

Context-dependent role of sirtuin 2 in inflammation

Neural Regeneration Research 2025年第3期20卷 682-694页

作者： NoemíSola-Sevilla Maider Garmendia-Berges MCarmen Mera-Delgado Elena Puerta Department of Pharmaceutical Sciences Division of PharmacologySchool of Pharmacy and NutritionUniversity of NavarraPamplonaSpain Navarra Institute for Health Research(IdiSNA) PamplonaSpain

sirtuin 2 is a member of the sirtuin family nicotinamide adenine dinucleotide(NAD~+)-dependent deacetylases, known for its regulatory role in different processes, including inflammation. In this context, sirtuin 2 has been involved in the modulation of key inflammatory signaling pathways and transcription factors by deacetylating specific targets, such as nuclear factor κB and nucleotide-binding oligomerization domain-leucine-rich-repeat and pyrin domain-containing protein 3(NLRP3). However, whether sirtuin 2-mediated pathways induce a pro-or an anti-inflammatory response remains controversial. sirtuin 2 has been implicated in promoting inflammation in conditions such as asthma and neurodegenerative diseases, suggesting that its inhibition in these conditions could be a potential therapeutic strategy. Conversely, arthritis and type 2 diabetes mellitus studies suggest that sirtuin 2 is essential at the peripheral level and, thus, its inhibition in these pathologies would not be recommended. Overall, the precise role of sirtuin 2 in inflammation appears to be context-dependent, and further investigation is needed to determine the specific molecular mechanisms and downstream targets through which sirtuin 2 influences inflammatory processes in various tissues and pathological conditions. The present review explores the involvement of sirtuin 2 in the inflammation associated with different pathologies to elucidate whether its pharmacological modulation could serve as an effective strategy for treating this prevalent symptom across various diseases.

关键词： interferon inflammation lipopolysaccharide neuroinflammation NLRP3 nuclear factorκB sirtuin 2

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

SIRT2 as a potential new therapeutic target for Alzheimer's disease

引用

Neural Regeneration Research 2024年第1期19卷 124-131页

作者： Noemi Sola-Sevilla Elena Puerta Department of Pharmacology and Toxicology Faculty of PharmacyUniversity of NavarraNavarra Institute for Health Research(IdiSNA)PamplonaSpain

Alzheimer's disease is the most common cause of dementia globally with an increasing incidence over the years,bringing a heavy burden to individuals and society due to the lack of an effective treatment.In this context,sirtuin 2,the sirtuin with the highest expression in the brain,has emerged as a potential therapeutic target for neurodegenerative diseases.This review summarizes and discusses the complex roles of sirtuin 2 in different molecular mechanisms involved in Alzheimer's disease such as amyloid and tau pathology,microtubule stability,neuroinflammation,myelin formation,autophagy,and oxidative stress.The role of sirtuin 2 in all these processes highlights its potential implication in the etiology and development of Alzheimer's disease.However,its presence in different cell types and its enormous variety of substrates leads to apparently contra dictory conclusions when it comes to understanding its specific functions.Further studies in sirtuin 2 research with selective sirtuin2 modulators targeting specific sirtuin 2 substrates are necessary to clarify its specific functions under different conditions and to validate it as a novel pharmacological target.This will contribute to the development of new treatment strategies,not only for Alzheimer's disease but also for other neurodegenerative diseases.

关键词： Alzheimer's disease amyloid autophagy memory neurodegenerative diseases neuroinflammation sirtuin 2 tau

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Upregulation of α-ENaC induces pancreatic β-cell dysfunction,ER stress,and SIRT2 degradation

引用

Journal of Biomedical Research 2024年第3期38卷 241-255页

作者： Xue Zhang Dan Zhang Lei Huo Xin Zhou Jia Zhang Min Li Dongming Su Peng Sun Fang Chen Xiubin Liang Department of Pathophysiology Nanjing Medical UniversityNanjingJiangsu 211166China Department of Pathology Nanjing Drum Tower Hospitalthe Affiliated Hospital of Nanjing University Medical SchoolNanjingJiangsu 210009China Key Laboratory of Human Functional Genomics of Jiangsu Province Department of Biochemistry and Molecular BiologyNanjing Medical UniversityNanjingJiangsu 211166China Department of Pathology Nanjing Medical UniversityNanjingJiangsu 211166China

Islet beta cells(β-cells)produce insulin in response to high blood glucose levels,which is essential for preserving glucose homeostasis.Voltage-gated ion channels inβ-cells,including Na+,K+,and Ca2+channels,aid in the release of insulin.The epithelial sodium channel alpha subunit(α-ENaC),a voltage-independent sodium ion channel,is also expressed in human pancreatic endocrine cells.However,there is no reported study on the function of ENaC in theβ-cells.In the current study,we found thatα-ENaC was expressed in human pancreatic glandule and pancreatic isletβ-cells.In the pancreas of db/db mice and high-fat diet-induced mice,and in mouse isletβ-cells(MIN6 cells)treated with palmitate,α-ENaC expression was increased.Whenα-ENaC was overexpressed in MIN6 cells,insulin content and glucose-induced insulin secretion were significantly reduced.On the other hand,palmitate injured isletβ-cells and suppressed insulin synthesis and secretion,but increasedα-ENaC expression in MIN6 cells.However,α-ENaC knockout(Scnn1a−/−)in MIN6 cells attenuatedβ-cell disorder induced by palmitate.Furthermore,α-ENaC regulated the ubiquitylation and degradation of sirtuin 2 inβ-cells.α-ENaC also modulatedβ-cell function in correlation with the inositol-requiring enzyme 1 alpha/X-box binding protein 1(IRE1α/XBP1)and protein kinase RNA-like endoplasmic reticulum kinase/C/EBP homologous protein(PERK/CHOP)endoplasmic reticulum stress pathways.These results suggest thatα-ENaC may play a novel role in insulin synthesis and secretion in theβ-cells,and the upregulation ofα-ENaC promotes isletβ-cell dysfunction.In conclusion,α-ENaC may be a key regulator involved in isletβ-cell damage and a potential therapeutic target for type 2 diabetes mellitus.

关键词： α-ENaC pancreaticβ-cells type 2 diabetes mellitus endoplasmic reticulum stress sirtuin 2

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

新型吲唑类sirtuin 2抑制剂的设计、合成及活性研究

引用

中国药物化学杂志 2021年第5期31卷 337-347页

作者：宋陈苏荟琳晏婕袁陈钱珊杨羚羚西华大学食品与生物工程学院四川成都610039

目的设计合成新型吲唑类SIRT2抑制剂并评价其抑制活性,获得吲唑类SIRT2抑制剂的初步构效关系。方法以非典型组蛋白去乙酰化酶SIRT2作为靶标,在前期研究基础上,通过合理环合的思路设计一系列新型吲唑类SIRT2潜在抑制剂;通过亲核取代、缩... 详细信息

目的设计合成新型吲唑类SIRT2抑制剂并评价其抑制活性,获得吲唑类SIRT2抑制剂的初步构效关系。方法以非典型组蛋白去乙酰化酶SIRT2作为靶标,在前期研究基础上,通过合理环合的思路设计一系列新型吲唑类SIRT2潜在抑制剂;通过亲核取代、缩合、还原胺化等反应合成吲唑类小分子目标化合物;采用课题组自主构建的基于荧光多肽底物(P2263)的筛选方法测试所合成的目标化合物在100μmol·L^(-1)和10μmol·L^(-1)浓度下对SIRT2的抑制率。结果与结论共合成17个目标化合物,均对SIRT2有不同程度的抑制作用,其中5个化合物在100μmol·L^(-1)浓度下抑制率大于50%,且化合物S5的抑制活性最佳,在100μmol·L^(-1)和10μmol·L^(-1)浓度下抑制率分别为70%和36%,与课题组早期报道的2-((4,6-嘧啶-2-基)硫)-N-苯乙酰胺类活性化合物(P4)抑制效果相当。本研究为发现新型特异性SIRT2小分子抑制剂提供了更多思路,且为课题组后续开发更高效的SIRT2抑制剂奠定了一定基础。

关键词：组蛋白去乙酰化酶 sirtuin 2 小分子抑制剂吲唑

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

SIRT2 interacts with DDX24 to promote nasopharyngeal carcinoma growth

引用

BIOCELL 2023年第11期47卷 2445-2452页

作者： HAIYING YUE CHUNHUI WANG HUIJUN ZHU QINGHUA DU JIAN LI XUE OU XIANGDE LI QIULU ZHONG YITING XIE DANJING LUO YIHE LI CHUNXIAO LIANG XUEMEI XU SONGNAN DU WENQI LIU Department of Radiotherapy The Second Affiliated Hospital of Guangxi Medical UniversityNanningChina

Background:Nasopharyngeal carcinoma(NPC)is one of the most prevalent cancers in Southeast Asia.sirtuin 2(SIRT2)is a member of the NAD+-dependent deacetylase family and has been shown to play important roles in numerous biological processes.However,Its function in NPC remains uncertain.The primary aim of this study is to clarify the role of SIRT2 in NPC.Methods:In this research,we examined the effect of SIRT2 silencing on NPC cell proliferation and colony formation using vitro NPC cell lines.Co-immunoprecipitation and mass spectrometry was applied to identify SIRT2-interacting proteins in NPC cells.Results:In comparison to nasopharyngeal epithelial NP69 cells,SIRT2 was up-regulated in multiple NPC cell lines,particularly in CNE2 cells.SIRT2 knockdown abrogated CNE2 cell proliferation and colony formation,whereas SIRT2 overexpression promoted HNE1 cell proliferation and colony formation.The SIRT2-interacting proteins were gathered in gene expression and regulation processes including RNA processing and translation.Among the SIRT2-interacting proteins,there were multiple DEAD-box(DDX)family members.Of note,silencing of DDX24 phenocopied the effect of SIRT2 knockdown on NPC growth.Overexpression of DDX24 restored SIRT2-depleted CNE2 cells to proliferative and colony formation.Conclusions:Our study indicates that SIRT2 can interact with DDX24 to enhance NPC growth.The clinical relevance of SIRT2 and DDX24 in NPC warrants further investigation.

关键词： Nasopharyngeal carcinoma sirtuin 2 DDX24 Proliferation

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Particulate matter 2.5 triggers airway inflammation and bronchial hyperresponsiveness in mice by activating the SIRT2-p65 pathway

引用

Frontiers of Medicine 2021年第5期15卷 750-766页

作者： Manling Liu Zhaoling Shi Yue Yin Yishi Wang Nan Mu Chen Li Heng Ma Qiong Wang Department of Physiology and Pathophysiology Fourth Military Medical UniversityXi’an 710032China Department of Pediatrics Second Affiliated Hospital of Shaanxi University of Chinese MedicineXianyang 712046China Department of Cardiovascular Medicine Xijing HospitalFourth Military Medical UniversityXi’an 710032China

Exposure to particulate matter 2.5(PM2.5)potentially triggers airway inflammation by activating nuclear factor-κB(NF-κB).sirtuin 2(SIRT2)is a key modulator in inflammation.However,the function and specific mechanisms of SIRT2 in PM2.5-induced airway inflammation are largely understudied.Therefore,this work investigated the mechanisms of SIRT2 in regulating the phosphorylation and acetylation of p65 influenced by PM2.5-induced airway inflammation and bronchial hyperresponsiveness.Results revealed that PM2.5 exposure lowered the expression and activity of SIRT2 in bronchial tissues.Subsequently,SIRT2 impairment promoted the phosphorylation and acetylation of p65 and activated the NF-κB signaling pathway.The activation of p65 triggered airway inflammation,increment of mucus secretion by goblet cells,and acceleration of tracheal stenosis.Meanwhile,p65 phosphorylation and acetylation,airway inflammation,and bronchial hyperresponsiveness were deteriorated in SIRT2 knockout mice exposed to PM2.5.Triptolide(a specific p65 inhibitor)reversed p65 activation and ameliorated PM2.5-induced airway inflammation and bronchial hyperresponsiveness.Our findings provide novel insights into the molecular mechanisms underlying the toxicity of PM2.5 exposure.Triptolide inhibition of p65 phosphorylation and acetylation could be an effective therapeutic approach in averting PM2.5-induced airway inflammation and bronchial hyperresponsiveness.

关键词： particulate matter 2.5 sirtuin 2 p65 airway inflammation bronchial hyperresponsiveness triptolide

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

14-Deoxygarcinol,a polyisoprenylated benzophenone from Garcinia cambogia,ameliorates inflammatory responses in adipose tissue via suppressing NLRP3 inflammasome

引用

中国药理学与毒理学杂志 2021年第10期35卷 759-759页

作者： CHEN Jia-li FENG Zhe-ling CHEN Cheng ZHU Jian-zhong LIN Li-gen State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacaoChina

OBJECTIVE Interleukin(IL)-1β,one of the principal inflammatory cytokines mainly secreted by monocytes and macrophages,is produced by cleavage of the inactive pro-IL^(-1)βprecursor by caspase-1 via the NLRP3 inflammasome complex.The fruits of Garcinia cambogia(Clusiaceae)are widely developed as health products for anti-obese purpose.14-deoxygarcinol(DOG)is a polyisoprenylated benzophenone from the fruits of G.cambogia,which showed potent anti-inflammatory effect in our previous study.The objective of this study was to explore the anti-inflammatory mechanism of DOG and its roles in alleviating adipose tissue inflammation and insulin resistance.METHODS The anti-inflammatory effect of DOG was evaluated on LPS plus nigericin-induced THP-1 macrophages.The expression of NLRP3 inflammasome complex proteins was analyzed by Western blotting,immunofluorescence staining and co-immunoprecipitation.The pro-inflammatory cytokines levels were determined by ELISA kits.RESULTS DOG increased the expression of sirtuin 2(SIRT2)deacetylase and enhanced its deacetylating activity to suppress the NLRP3 inflammasome activation and IL^(-1)βsecretion in THP-1 macrophages.Moreover,DOG attenuated macrophage conditioned medium-induced inflammatory responses in adipocytes and blocked THP-1 macrophages migration towards 3T3-L1 adipocytes.CONCLUSION DOG attenuated the inflammatory crosstalk between macrophages and adipocytes through SIRT2-mediated NLRP3 inflammasome inhibition,which might be used for the treatment of adipose tissue inflammation-related metabolic disorders.

关键词： 14-deoxygarcinol sirtuin 2 interleukin-1β macrophages NLRP3 inflammasome

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：