Cardioprotective Role of SIRT5 in Response to Acute Ischemia Through a Novel Liver-Cardiac Crosstalk Mechanism.
Cardioprotective Role of SIRT5 in Response to Acute Ischemia Through a Novel Liver-Cardiac Crosstalk Mechanism.
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SIRT5 通过新型肝-心脏串扰机制响应急性缺血的心脏保护作用
DOI：
10.3389/fcell.2021.687559
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发表时间：
2021
影响因子：
5.5
通讯作者：
Wei T
中科院分区：
文献类型：
--
作者：
Zhou B;Xiao M;Hu H;Pei X;Xue Y;Miao G;Wang J;Li W;Du Y;Zhang P;Wei T
蛋白质翻译后修饰在心血管疾病中起重要作用。作者以前的报告表明，琥珀酰化和戊二酰化蛋白在急性心肌梗死（AMI）患者血清中的丰度明显低于健康志愿者，提示蛋白酰化与AMI之间存在潜在的关系。Sirtuin 5（SIRT 5）有助于去除丙二酰、琥珀酰和戊二酰修饰;然而，其对AMI的影响尚不清楚。在本研究中，比较了AMI小鼠模型中SIRT 5的水平。结果显示心肌梗死后肝脏SIRT 5升高。产生肝细胞特异性SIRT 5过表达小鼠（肝SIRT 5 OE）以解决肝SIRT 5在AMI中的可能参与。在肝脏SIRT 5 OE小鼠和野生型（WT）小鼠之间比较了实验性心肌梗死模型中心肌梗死、心肌纤维化和心脏功能的面积。肝脏SIRT 5 OE小鼠显示出比WT小鼠显著更小的心肌梗死和心肌纤维化面积。SIRT 5 OE小鼠AMI后血和肝组织中FGF 21的含量明显高于WT小鼠。质谱分析结果显示，SIRT 5 OE小鼠肝线粒体中调节三羧酸循环、氧化磷酸化和脂肪酸β-氧化途径的蛋白质水平增加。这些发现表明，SIRT 5可能通过肝-心串扰机制在急性缺血反应中表现出心脏保护作用，可能是通过增加FGF 21的分泌和改善能量代谢。
Protein posttranslational modifications play important roles in cardiovascular diseases. The authors’ previous report showed that the abundance of succinylated and glutarylated proteins was significantly lower in the serum of patients with acute myocardial infarction (AMI) than in that of healthy volunteers, suggesting a potential relationship between protein acylation and AMI. Sirtuin 5 (SIRT5) facilitates the removal of malonyl, succinyl, and glutaryl modification; however, its effects on AMI remain unknown. In this study, the levels of SIRT5 in AMI mouse model was compared. Results showed elevated hepatic SIRT5 after myocardial infarction. Hepatocyte-specific SIRT5 overexpressing mice (liver SIRT5 OE) were generated to address the possible involvement of hepatic SIRT5 in AMI. The areas of myocardial infarction, myocardial fibrosis, and cardiac function in a model of experimental myocardial infarction were compared between liver SIRT5 OE mice and wild-type (WT) mice. The liver SIRT5 OE mice showed a significantly smaller area of myocardial infarction and myocardial fibrosis than the WT mice. The fibroblast growth factor 21 (FGF21) in the blood and myocardium of liver SIRT5 OE mice after AMI was markedly elevated compared with that in WT mice. The results of mass spectrometry showed increased levels of proteins regulating tricarboxylic acid cycle, oxidative phosphorylation, and fatty acid β-oxidation pathways in the liver mitochondria of liver SIRT5 OE mice. These findings showed that SIRT5 may exhibit a cardioprotective effect in response to acute ischemia through a liver-cardiac crosstalk mechanism, probably by increasing the secretion of FGF21 and the improvement of energy metabolism.
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SIRT5 使代谢相关蛋白脱酰并减轻 ob/ob 小鼠的肝脂肪变性
影响因子：
11.1
作者：
Du Y;Hu H;Qu S;Wang J;Hua C;Zhang J;Wei P;He X;Hao J;Liu P;Yang F;Li T;Wei T
通讯作者：
Wei T
影响因子：
4.8
作者：
Hershberger, Kathleen A.;Abraham, Dennis M.;Hirschey, Matthew D.
通讯作者：
Hirschey, Matthew D.
影响因子：
4.8
作者：
Hershberger, Kathleen A.;Abraham, Dennis M.;Hirschey, Matthew D.
通讯作者：
Hirschey, Matthew D.
SIRT5 调节线粒体赖氨酸琥珀酰组和代谢网络。
影响因子：
29
作者：
Rardin MJ;He W;Nishida Y;Newman JC;Carrico C;Danielson SR;Guo A;Gut P;Sahu AK;Li B;Uppala R;Fitch M;Riiff T;Zhu L;Zhou J;Mulhern D;Stevens RD;Ilkayeva OR;Newgard CB;Jacobson MP;Hellerstein M;Goetzman ES;Gibson BW;Verdin E
通讯作者：
Verdin E
DOI：
10.1126/science.1179689
发表时间：
2010-02-19
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Zhao S;Xu W;Jiang W;Yu W;Lin Y;Zhang T;Yao J;Zhou L;Zeng Y;Li H;Li Y;Shi J;An W;Hancock SM;He F;Qin L;Chin J;Yang P;Chen X;Lei Q;Xiong Y;Guan KL
通讯作者：
Guan KL