FAM3A mediates PPARγ's protection in liver ischemia-reperfusion injury by activating Akt survival pathway and repressing inflammation and oxidative stress.
FAM3A mediates PPARγ's protection in liver ischemia-reperfusion injury by activating Akt survival pathway and repressing inflammation and oxidative stress.
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FAM3A 通过激活 Akt 存活通路、抑制炎症和氧化应激介导 PPAR gamma 对肝脏缺血再灌注损伤的保护作用
DOI：
10.18632/oncotarget.17805
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发表时间：
2017-07-25
期刊：
影响因子：
--
通讯作者：
Yang J
中科院分区：
文献类型：
--
作者：
Chen Z;Wang J;Yang W;Chen J;Meng Y;Geng B;Cui Q;Yang J
FAM 3A是一种新的线粒体蛋白，其生物学功能在很大程度上仍然未知。本研究旨在探讨FAM 3A在肝脏缺血再灌注损伤中的作用及其机制。在IRI后的小鼠肝脏中，FAM 3A表达增加。与WT小鼠相比，FAM 3A缺陷小鼠在肝脏IRI后表现出加重的肝损伤，血清AST、ALT、MPO、MDA和氧化应激水平升高。与IRI后WT小鼠肝脏相比，FAM 3A缺陷小鼠肝脏的ATP含量、Akt活性和抗凋亡蛋白表达降低，而凋亡蛋白表达、炎症和氧化应激增加。罗格列酮预处理可保护野生型小鼠的肝脏IRI，但对FAM 3A缺陷型小鼠无效。在培养的肝细胞中，FAM 3A过表达保护免受氧化应激诱导的细胞死亡，而FAM 3A缺乏则加重了氧化应激诱导的细胞死亡。FAM 3A的上调或过表达以P2受体依赖的方式抑制缺氧/复氧诱导的凋亡基因的激活和肝细胞死亡。FAM 3A缺乏减弱了罗格列酮对培养肝细胞中Akt活化和细胞存活的有益作用。总的来说，FAM 3A通过激活Akt存活途径、抑制炎症和减弱氧化应激来保护肝脏IRI。此外，PPARγ激动剂对肝脏IRI的保护作用依赖于FAM 3A-ATP-Akt通路。
FAM3A is a novel mitochondrial protein, and its biological function remains largely unknown. This study determined the role and mechanism of FAM3A in liver ischemia-reperfusion injury (IRI). In mouse liver after IRI, FAM3A expression was increased. FAM3A-deficient mice exhibited exaggerated liver damage with increased serum levels of AST, ALT, MPO, MDA and oxidative stress when compared with WT mice after liver IRI. FAM3A-deficient mouse livers had a decrease in ATP content, Akt activity and anti-apoptotic protein expression with an increase in apoptotic protein expression, inflammation and oxidative stress when compared WT mouse livers after IRI. Rosiglitazone pretreatment protected against liver IRI in wild type mice but not in FAM3A-deficient mice. In cultured hepatocytes, FAM3A overexpression protected against, whereas FAM3A deficiency exaggerated oxidative stress-induced cell death. FAM3A upregulation or FAM3A overexpression inhibited hypoxia/reoxygenation-induced activation of apoptotic gene and hepatocyte death in P2 receptor-dependent manner. FAM3A deficiency blunted rosiglitazone's beneficial effects on Akt activation and cell survival in cultured hepatocytes. Collectively, FAM3A protects against liver IRI by activating Akt survival pathways, repressing inflammation and attenuating oxidative stress. Moreover, the protective effects of PPARγ agonist(s) on liver IRI are dependent on FAM3A-ATP-Akt pathway.
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影响因子：
2.9
作者：
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