Pioglitazone Protects Against Renal Ischemia-Reperfusion Injury via the AMP-Activated Protein Kinase-Regulated Autophagy Pathway.
Pioglitazone Protects Against Renal Ischemia-Reperfusion Injury via the AMP-Activated Protein Kinase-Regulated Autophagy Pathway.
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吡格列酮通过 AMP 激活的蛋白激酶调节的自噬途径预防肾缺血再灌注损伤
DOI：
10.3389/fphar.2018.00851
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发表时间：
2018
影响因子：
5.6
通讯作者：
Hu H
中科院分区：
文献类型：
--
作者：
Chen W;Xi X;Zhang S;Zou C;Kuang R;Ye Z;Huang Y;Hu H
肾缺血再灌注损伤(IRI)是导致急性肾功能衰竭的主要原因。我们以前的研究表明，吡格列酮是一种用于治疗2型糖尿病的过氧化物酶体增殖物激活受体-γ激动剂，对肾脏缺血再灌注具有保护作用；然而，其肾脏保护作用的分子机制尚不清楚。在这项研究中，我们研究了AMP激活蛋白激酶(AMPK)调节的自噬在吡格列酮对IRI肾脏保护中的作用。为了研究吡格列酮是否能保护肾脏细胞免受IRI的影响，我们采用了活体肾脏IRI模型。TUNEL法检测大鼠肾脏细胞凋亡率。免疫印迹法检测肾组织中AMPK、自噬相关蛋白和caspase-3/8蛋白的表达。在大鼠IRI模型中，吡格列酮可降低升高的血肌酐和尿素氮，改善肾脏组织学评分，减轻细胞损伤。吡格列酮还可增加IRI大鼠肾脏AMPK的磷酸化，抑制p62和caspase-3/8蛋白的裂解，并激活自噬相关蛋白Lc3 II和Beclin-1。此外，GW9662作为PPAR-γ的选择性抑制剂，可抑制吡格列酮的保护作用。这些结果表明，吡格列酮通过激活AMPK调节的自噬信号通路对肾脏IRI起到保护作用。
Renal ischemia-reperfusion injury (IRI) is a major cause of acute renal failure. Our previous studies have shown that pioglitazone, a peroxisome proliferators-activated receptor (PPAR)-γ agonist used in type 2 diabetes, protects against renal IRI; however, the molecular mechanism underlying the renoprotective effects of pioglitazone is still unclear. In this study, we investigated the role of AMP-activated protein kinase (AMPK)-regulated autophagy in renoprotection by pioglitazone in IRI. To investigate whether pioglitazone protects renal cells from IRI, an in vivo renal IRI model was used. Cell apoptosis in the kidneys was determined by TUNEL staining. Western blotting was used to determine the expression of AMPK, autophagy-related proteins, and caspase-3/8 proteins in the kidneys. In a rat model of IRI, pioglitazone decreased the increased serum creatinine and urea nitrogen, improved renal histological score, and decreased the cell injury. Pioglitazone also increased AMPK phosphorylation, inhibited p62 and cleaved caspase-3/8 proteins, and activated autophagy-related proteins LC3 II and Beclin-1 in the kidneys of IRI rats. Moreover, GW9662, as a selective inhibitor of PPAR-γ, inhibited the protective effects of pioglitazone. These results suggest that pioglitazone exerts its protective effects in renal IRI via activation of an AMPK-regulated autophagy signaling pathway.
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AMP激活的蛋白激酶对ULK1（HATG1）的磷酸化将能量传感连接到线粒体。
DOI：
10.1126/science.1196371
发表时间：
2011-01-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Egan DF;Shackelford DB;Mihaylova MM;Gelino S;Kohnz RA;Mair W;Vasquez DS;Joshi A;Gwinn DM;Taylor R;Asara JM;Fitzpatrick J;Dillin A;Viollet B;Kundu M;Hansen M;Shaw RJ
通讯作者：
Shaw RJ
影响因子：
21.3
作者：
通讯作者：
--
影响因子：
3.7
作者：
Conde E;Alegre L;Blanco-Sánchez I;Sáenz-Morales D;Aguado-Fraile E;Ponte B;Ramos E;Sáiz A;Jiménez C;Ordoñez A;López-Cabrera M;del Peso L;de Landázuri MO;Liaño F;Selgas R;Sanchez-Tomero JA;García-Bermejo ML
通讯作者：
García-Bermejo ML
线粒体功能障碍和肝缺血/再灌注损伤中的自噬。
影响因子：
--
作者：
Go KL;Lee S;Zendejas I;Behrns KE;Kim JS
通讯作者：
Kim JS
影响因子：
0.7
作者：
Malek M;Nematbakhsh M
通讯作者：
Nematbakhsh M