更新于：2024-11-01

SIRT5

更新于：2024-11-01

基本信息

别名

NAD-dependent protein deacylase sirtuin-5, mitochondrial、Regulatory protein SIR2 homolog 5、SIR2-like protein 5

+ [5]

简介

NAD-dependent lysine demalonylase, desuccinylase and deglutarylase that specifically removes malonyl, succinyl and glutaryl groups on target proteins (PubMed:21908771, PubMed:22076378, PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to the regulation of blood ammonia levels during prolonged fasting: acts by mediating desuccinylation and deglutarylation of CPS1, thereby increasing CPS1 activity in response to elevated NAD levels during fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating its desuccinylation, leading to reduced reactive oxygen species (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation (PubMed:29180469). Modulates ketogenesis through the desuccinylation and activation of HMGCS2 (By similarity). Has weak NAD-dependent protein deacetylase activity; however this activity may not be physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) and a number of other proteins in vitro such as UOX.

关联

项与 SIRT5 相关的药物

Nicotinamide riboside/Pterostilbene

靶点

NAD+ x SIRT5

作用机制

NAD+调节剂 [+1]

在研机构

Elysium Health, Inc.初创企业

原研机构

Elysium Health, Inc.初创企业

在研适应症

主动脉瘤 [+1]

非在研适应症

肌萎缩侧索硬化 [+1]

最高研发阶段临床2期

首次获批国家/地区-

首次获批日期1800-01-20

Compound 58(Xihua University)

Compound 58(西华大学)

靶点

SIRT5

作用机制

SIRT5抑制剂

在研机构

西华大学

原研机构

西华大学

在研适应症

急性肾损伤

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

XHU-58

靶点

SIRT5

作用机制

SIRT5抑制剂

在研机构

西华大学

原研机构

西华大学

在研适应症

急性肾损伤

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

项与 SIRT5 相关的临床试验

CTRI/2024/01/061558 / Not yet recruiting临床4期IIT

A Comparative Study to Assess the Effectiveness of Homoeopathic Medicines Selected on Basis of Totality of Symptoms vis-à-vis Body Language in The Treatment of Chronic Respiratory Diseases - NIL

开始日期2024-01-27

申办/合作机构-

NCT06196398 / RecruitingN/AIIT

Effects of Medical Treatment of Intracranial Atherosclerotic Diseases Based on Magnetic Resonance Fractional Flow Reserve

This multicenter prospective cohort study aims to compare the difference in the effects of medical treatment within 1 year between the two groups of ICAS patients divided hemodynamically by Magnetic Resonance Fractional Flow Reserve. PC MRA will be applied for FFR measurement. The primary outcome is the composite of ischemic stroke or death related to the qualifying artery territory for 1 year.

开始日期2023-01-01

申办/合作机构

首都医科大学宣武医院

NCT04841499 / CompletedN/AIIT

Effects of a Seven-day BASIS™ Supplementation on Menopausal Syndromes and Measurements of the Urinary Vitamin B3 and Estradiol Levels in Pre-, Peri- and Post-menopause

The purpose of this study is to determine whether a short supplementation (7days) with BASIS™ increases the natural production of estradiol, measured in urinary waste. The overall objective is to determine whether through increased estradiol levels, the undesirable menopausal effects, assessed via questionnaires, are mitigated by a short-term supplementation with BASIS™

开始日期2021-04-05

申办/合作机构

University of South Alabama

[+1]

100 项与 SIRT5 相关的临床结果

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100 项与 SIRT5 相关的转化医学

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0 项与 SIRT5 相关的专利（医药）

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537

项与 SIRT5 相关的文献（医药）

2024-12-31·Clinical and Experimental Hypertension

SIRT5-mediated PRKAA2 succinylation ameliorates apoptosis of human placental trophoblasts in hypertensive disorder complicating pregnancy

Article

作者: Liu, Guangman ; Zheng, Lili ; Yang, Mo ; Qi, Yuyan ; Ren, Feifei ; Li, Jia ; Li, Aijie

PURPOSEHypertensive disorder complicating pregnancy (HDCP) is a serious clinical disorder syndrome during pregnancy. This study aims at finding novel targets for HDCP therapy.METHODSHDCP-related mRNAs were firstly screened out and subjected to gene enrichment analysis. We chose protein kinase AMP-activated catalytic subunit alpha 2 (PRKAA2) as the research object. Thirty-nine HDCP patients at 32 to 40 weeks of gestation were selected as the HDCP group, and 39 normal controls who received cesarean section delivery at 37-42 weeks of pregnancy were enrolled in this study. Chorionic villi samples were collected within 30 min of delivery. The apoptosis of isolated placental trophoblasts was monitored to investigate the regulatory role of PRKAA2.RESULTSPRKAA2 expression was further proven to be enhanced in the placental tissues of HDCP patients compared with that of normal puerpera. Subsequently, the results of flow cytometry analysis and western blot indicated that PRKAA2 overexpression accelerated primary placental cell apoptosis, while its knockdown attenuated cell apoptosis. Mechanistically, we determined that the level of PRKAA2 succinylation was elevated in the placental tissue of HDCP patients. Through in vitro succinylation assay and mutagenesis, we confirmed that sirtuin 5 (SIRT5) interacts with PRKAA2 at K69 and K260 to induce PRKAA2 desuccinylation. SIRT5 regulated primary HDCP cell apoptosis through PRKAA2. Finally, the animal study revealed that PRKAA2 elevates the systolic blood pressure of HDCP rat model.CONCLUSIONOur findings indicated that SIRT5-mediated PRKAA2 succinylation modulates placental cell apoptosis in HDCP, suggesting that PRKAA2 is a potential therapeutic target for HDCP treatment.

2024-12-31·Redox Report

Angelica keiskei water extract Mitigates Age-Associated Physiological Decline in Mice

Article

作者: Su, Min ; Li, Mengnan ; Kang, Ning ; Hou, Yunlong ; Liu, Huan ; Hou, Bin ; Wang, Lu ; Li, Xiaoyan ; Sun, Mingzhe ; Jia, Zhenhua ; Wang, Chao ; Guo, Zhifang ; Wei, Gang ; Wang, Tongxing

OBJECTIVEAngelica keiskei is a medicinal and edible plant that has been reported to possess potent antioxidant properties in several in vitro models, but its effectiveness on naturally aging organisms is still lacking. This study explores the antioxidant and health-promoting effects of Angelica keiskei in naturally aging mice.METHODSWe treated 48-week-old mice with Angelica keiskei water extract (AKWE) 30 days, and measured indicators related to aging and antioxidants. In addition, we conducted network pharmacology analysis, component-target molecular docking, real-time PCR, and MTS assays to investigate relevant factors.RESULTSThe results indicated that administration of AKWE to mice led to decrease blood glucose levels, improve muscle fiber structure, muscle strength, gait stability, and increase levels of glutathione and superoxide dismutase in serum. Additionally, it decreased pigmentation of the heart tissues. Angelica keiskei combats oxidative stress by regulating multiple redox signaling pathways, and its ingredients Coumarin and Flavonoids have the potential to bind to SIRT3 and SIRT5.CONCLUSIONSOur findings indicated the potential of Angelica keiskei as a safe and effective dietary supplement to combat aging and revealed the broad prospects of medicinal and edible plants for addressing aging and age-related chronic diseases.

2024-11-01·Cellular Signalling

Transcriptional activation of SIRT5 by FOXA1 reprograms glycolysis to facilitate the malignant progression of diffuse large B-cell lymphoma

Article

作者: Jin, Shenhe ; Lu, Peng ; Zhang, Jin ; Chen, Xiaochang ; Zhang, Ye

项与 SIRT5 相关的新闻（医药）

2024-09-11

·奇点网

《细胞·代谢》：关节炎为什么时好时坏？南方医科大学团队发现，饮食可以通过特定肠菌调节类风湿关节炎炎症节律丨科学大发现

*仅供医学专业人士阅读参考类风湿关节炎（RA）是一种常见的慢性自免病，全身性的炎症和关节损伤是它最主要的特征。类风湿关节炎的昼夜节律非常明显，患者普遍存在早晨症状最严重，并在一天内逐渐减轻的现象。我们知道，这样的症状可能受到昼夜节律、激素水平变化、免疫系统激活等多种因素的影响，了解其中的影响因素，能够帮助患者在药物治疗之外，尽可能多地通过改变生活方式来改善生活质量。节律会受到多种环境因素调节，例如光照、运动、摄入食物等等。今日，南方医科大学团队在《细胞·代谢》杂志发表论文，研究者们发现，饮食会通过肠菌调控类风湿关节炎炎症。具体来说，狄氏副拟杆菌（Parabacteroides distasonis ）会通过其代谢产物黄豆黄素（glycitein，GLY）抑制SIRT5-NK-κB炎症轴。简单来说，在特定肠菌的帮助下，吃饭也能抗炎。看来，在类风湿关节炎的治疗中，吃饭应该是非常重要的一环。论文题图研究者首先对类风湿关节炎患者的炎症节律进行了分析。他们招募了41名患者，30名健康对照，测量了每个个体在一天中00:00、06:00、12:00、18:00四个时间点的血清白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的水平。类风湿关节炎患者的两种细胞因子水平表现出了明显的节律模式，在夜间升高，06:00达到峰值，随后下降。对患者的关节液样本分析显示，与晚上18:00-20:00收集的样本相比，早上06:00-08:00收集的样本中，中性粒细胞比例更高、单核细胞上CD86表达增加，说明促炎巨噬细胞分化。在胶原诱导的骨关节炎（CIA）模式小鼠中，研究者也观察到了类似的炎症节律：炎症因子和炎性免疫细胞在休息阶段增加、在活跃阶段减少。 RA患者中存在炎症节律（上）在CIA小鼠中观察到了明显的炎症节律（下）有趣的是，当研究者改变了小鼠的光照时间，人为让它们昼夜颠倒，小鼠的炎症节律并未变化；但改变小鼠的进食时间，小鼠的炎症节律便随之发生了改变。看来，在影响炎症节律上，吃饭时间比昼夜影响更大。小鼠炎症节律因进食时间而变提到吃，立刻就会想到肠道微生物。果然，炎症节律中也有肠菌的参与，当研究者用抗生素消除小鼠的肠菌，进食就不再改变炎症节律了。抗生素可以消除进食带来的炎症节律变化究竟是什么菌在作怪？研究者分析了CIA小鼠和类风湿关节炎患者的粪便微生物组波动，发现副拟杆菌、拟杆菌和乳杆菌三个菌属受影响最大，其中狄氏副拟杆菌表现出了明显的受进食影响的节律变化，看来就是它了。原来，狄氏副拟杆菌中的β-葡萄糖苷酶（β-GC）可以代谢食物中的异黄酮生成黄豆黄素（GLY），GLY对关节有抗炎、抗氧化、调节免疫、镇痛和关节保护作用。具体来说，GLY可以上调SIRT家族表达、降低NF-κB亚基磷酸化水平，通过抑制SIRT5-NF-κB通路发挥抗炎作用。遗憾的是，这项研究成果并未能够给类风湿关节炎患者提供明确的饮食建议，研究中涉及的代谢物未经安全性研究也不建议大家盲目地去补充。不过一些其他的可靠研究已经给出了有效的抗炎食物单品，例如富含omega-3脂肪酸的鱼类和亚麻籽、富含抗氧化物质的水果和蔬菜、含有多酚的各种豆制品绿茶和浆果，对于类风湿关节炎患者来说都是不错的食物，可以多吃。相反，大量的红肉和添加糖会促进炎症环境，可能加重类风湿关节炎的症状，就不建议吃太多了。奇点糕近期推出了《2024ASCO年会深度盘点》课程，为大家系统盘点了2024ASCO年会上实体瘤领域的重磅进展，让您在100分钟内迅速深入把握前沿。长按识别下图中的二维码即可购买，购买后您可以在「奇点网小程序」收听，或下载奇点网「医学奇点」苹果客户端收听。如果遇到任何技术问题大家可以戳我们下图中的客服小伙伴来解决~~ 参考资料： [1]https://www.cell.com/cell-metabolism/abstract/S1550-4131(24)00334-6 本文作者丨代丝雨

临床研究ASCO会议临床结果

2024-05-30

·精准药物

药物筛选中心（暨南大学）对外提供新药筛选服务

咨询合作药物筛选中心（暨南大学），隶属于暨南大学药学院公共科研平台。中心拥有Echo550微量液体超声转移工作站等先进的自动化药物筛选仪器，前期支撑的多个激酶抑制剂已经产业转化及发表JMC等高水平论文。目前，筛选中心建有激酶、蛋白酶、HDAC、COX、GPCR、报告基因、病毒、细菌等筛选模型，能够开展肿瘤、神经系统疾病、心脑血管病、糖尿病、病毒和细菌感染性疾病等领域相关靶标、细胞、机制的筛选和研究，每天能够完成数万次的新药筛选反应。已建立的药物筛选模型1）蛋白水平：激酶：Abl, ABL(M351T), ABL(H396P), ABL(Y253F), ABL1 (E255K), ABL1 (G250E), ABL(Q252H), AKT1, AKT2, AKT3, ALK, ALK5, AuroraA, AuroraB, AXL, BRAF, BRAF(V599E), BTK, DDR1, DDR2, EGFR, EGFR (T790M), EGFR(L858R), EGFR(L861Q), EGFR(T790ML858R), EGFR(D746-750), EGFR(D746-750/T790M), Flt3, FLT3(D835Y), FGFR1, FGFR2, FGFR3, FGFR4, Her2, Her4, KIT, MET, IGF-1R, FGFR1, JAK1, JAK2, JAK3, MAPK10, MAPK14, mTOR, TrkA, TrkB, TrkC,TYK2, KDR, SRC, PDGFRa, PDGFRA(D842V), PDGFRb, RET, ZAK。蛋白酶：MMP-1, MMP-2, MMP-3, MMP-9, MMP-13, MMP-14, ADAM5, ADAM10, ADAMTS13, TACE/ADAM17, Furin, Cathepsin E, Cathepsin D, BACE-1, DDP4, DDP8, DDP9, HIV protease-1, PMVII，PMVIV。HDACs：HDAC1, HDAC2, HDAC3, HDAC4, HDAC5, HDAC6, HDAC7, HDAC8, HDAC9, HDAC10, HDAC11, Sirt1, Sirt2, Sirt3, Sirt4, Sirt5, Sirt6。2）肿瘤细胞活性：近500种肿瘤细胞系；基于Ba/F3的耐药模型3）抗病毒/菌药物筛选：EV71和HSV病毒活性筛选模型；金黄色葡萄球菌、大肠杆菌和沙门氏杆菌等4）体内药效：移植瘤模型对外服务1）体外活性筛选（单剂量抑制率；多剂量IC50）；2）体内药效；3）机制研究；4）药代动力学研究；5）化合物工艺优化、大量订制。咨询合作

临床1期

2024-03-18

·生物谷

哈尔滨医科大学发现SIRT5治疗可能是一种有希望的可以减轻糖尿病性心肌病的靶点

本研究揭示了sirt5介导的GSTP1赖氨酸脱酰化在DCM小鼠氧化应激和焦亡中起保护作用的新机制。具体来说，SIRT5在心脏保护中的关键作用似乎至关重要。糖尿病性心肌病(Diabetic cardiomyopathy, DCM)是糖尿病引起的可导致心力衰竭的病理生理状况。DCM最初表现为心肌纤维化、重构功能不全、舒张功能不全，后来表现为收缩功能不全，最终表现为临床心力衰竭。焦亡是一种程序性细胞死亡，由细菌、病原体或其内毒素激活，在包括DCM在内的心血管疾病的发病机制中起着重要作用。在本研究中研究者假设DCM中刺激的氧化应激诱导NLRP3的激活和随后的焦亡，从而控制心肌细胞的死亡和成纤维细胞的激活。图片来源：https://pubmed.ncbi.nlm.nih.gov/38169591/ 近日，来自哈尔滨医科大学的研究者们在Int. J. Biol. Sci.杂志上发表了题为“SIRT5-related lysine demalonylation of GSTP1 contributes to cardiomyocyte pyroptosis suppression in diabetic cardiomyopathy”的文章，该研究表明SPI1通过转录激活SIRT5介导GSTP1 mal - lyss修饰和蛋白稳定性，从而改善dcm相关的心肌损伤。 SIRT5 (Sirtuin 5, SIRT5)定位于线粒体，由于SIRT5的缺失促进了线粒体蛋白的全局琥珀酰化和丙二酸化，因此已被确定为线粒体中的蛋白质去琥珀酰化酶和去丙烯酰化酶。研究者研究了SIRT5在糖尿病性心肌病(DCM)中的作用，并确定了该过程中赖氨酸脱酰化的机制。研究者用DCM诱导野生型和SIRT5基因敲除小鼠，提取原代心肌细胞和心脏成纤维细胞进行高糖(HG)处理。SIRT5缺乏加重了DCM小鼠的心肌损伤，加重了hg诱导的心肌细胞氧化应激和线粒体功能障碍，加剧了心肌细胞衰老、焦亡和DNA损伤。 dcm诱导的SIRT5缺失降低了谷胱甘肽s -转移酶P (GSTP1)蛋白的稳定性，表现为GSTP1的赖氨酸丙二酰化(Mal-Lys)修饰显著增加。SIRT5过表达可减轻dcm相关心肌损伤，而GSTP1下调可逆转这一作用。DCM中SIRT5转录减少是由于SPI1的下调。SPI1促进SIRT5的转录，从而改善dcm相关的心肌损伤。然而，SIRT5缺失导致SPI1的保护作用显著逆转。 SPI1通过促进SIRT5的转录和介导GSTP1的赖氨酸脱酰化，抑制氧化应激诱导的NLRP3活化和随后的细胞焦亡，并减弱焦亡诱导的心脏成纤维细胞活化和ECM合成的示意图图片来源：https://pubmed.ncbi.nlm.nih.gov/38169591/ 综上所述，本研究揭示了sirt5介导的GSTP1赖氨酸脱酰化在DCM小鼠氧化应激和焦亡中起保护作用的新机制。具体来说，SIRT5在心脏保护中的关键作用似乎至关重要。此外，本研究结果证实SIRT5的下调是由SPI1缺失引起的。本研究报道的基础知识提供了一种策略，即SIRT5治疗可能是一种有希望的药物干预，可以减轻DCM中的氧化应激和焦亡。（生物谷 Bioon.com）参考文献 Can Wei et al. SIRT5-related lysine demalonylation of GSTP1 contributes to cardiomyocyte pyroptosis suppression in diabetic cardiomyopathy. Int J Biol Sci. 2024 Jan 1;20(2):585-605. doi: 10.7150/ijbs.83306.