Proteomic study on the protective mechanism of fibroblast growth factor 21 to ischemia-reperfusion injury
Proteomic study on the protective mechanism of fibroblast growth factor 21 to ischemia-reperfusion injury
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成纤维细胞生长因子21对缺血再灌注损伤保护机制的蛋白质组学研究
DOI：
10.1139/cjpp-2012-0441
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发表时间：
2013-11-01
影响因子：
2.1
通讯作者：
Li, Xiao Kun
中科院分区：
文献类型：
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作者：
Cong, Wei-Tao;Ling, Jin;Li, Xiao Kun
成纤维细胞生长因子-21是3T3-L1脂肪细胞中一种新的胰岛素非依赖性葡萄糖转运调节剂，在糖尿病啮齿动物模型中具有降糖和甘油三酯作用。在本研究中，我们发现成纤维细胞生长因子-21能显著减轻缺血再灌注(I/R)对H9c2细胞(大鼠心脏)的损伤。然而，目前还不清楚哪些信号转导途径参与了成纤维细胞生长因子-21的心脏保护作用。因此，本研究旨在探讨成纤维细胞生长因子-21诱导细胞凋亡的可能机制。结果表明，成纤维细胞生长因子21通过降低超氧阴离子水平，通过激活Akt磷酸化抑制糖原合成酶K3β，恢复ATP合成酶丙酮酸激酶同工酶M1和蛋白激酶C的水平，从而预防与I/R损伤相关的氧化应激和细胞凋亡，从而改善能量供应。综上所述，我们得出结论，成纤维细胞生长因子-21主要通过Akt-GSK-3β-caspase-3依赖的途径保护H9c2细胞免受I/R损伤，防止氧化应激，恢复能量供应。
Fibroblast growth factor (FGF)-21 is a novel regulator of insulin-independent glucose transport in 3T3-L1 adipocytes and has glucose and triglyceride lowering effects in rodent models of diabetes. In this study, we found that FGF-21 can significantly attenuate ischemia-reperfusion (I/R) induced damage in H9c2 cells (rat heart). However, it is unclear which signal transduction pathway is involved in the cardioprotective effect of FGF-21. Thus, this study was designed to investigate the potential mechanism induced by FGF-21. The results showed that FGF-21 treatment prevented the oxidative stress and apoptosis associated with I/R damage by reducing the levels of superoxide anions, inhibiting glycogen synthase kinase (GSK) 3 beta by activating Akt phosphorylation, and recovering the levels of ATP synthase pyruvate kinase isozymes M1 and protein kinase C, thereby improving energy supply. In summary, we conclude that FGF-21 protects H9c2 cells against I/R injury mainly through the Akt-GSK-3 beta-caspase-3 dependent pathway, preventing oxidative stress, and recovery of the energy supply.