PI3K/Akt/FoxO3a signaling mediates cardioprotection of FGF-2 against hydrogen peroxide-induced apoptosis in H9c2 cells
PI3K/Akt/FoxO3a signaling mediates cardioprotection of FGF-2 against hydrogen peroxide-induced apoptosis in H9c2 cells
复制标题
PI3K/Akt/FoxO3a 信号介导 FGF-2 对 H9c2 细胞过氧化氢诱导的细胞凋亡的心脏保护作用
DOI：
10.1007/s11010-016-2658-5
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发表时间：
2016-03-01
影响因子：
4.3
通讯作者：
Jiang, Zhi-Sheng
中科院分区：
文献类型：
--
作者：
Liu, Mi-Hua;Li, Guo-Hua;Jiang, Zhi-Sheng
心血管疾病是一个日益严重的全球公共卫生问题。氧化应激被认为是病理生理的关键调节因子之一，最终导致心血管疾病。然而，FGF-2在心血管疾病中拯救细胞免受氧化应激损伤的机制尚未完全阐明。本研究旨在探讨FGF-2对H2 O2诱导的H9 c2心肌细胞凋亡的保护作用及其可能的信号通路。H2 O2诱导H9 c2心肌细胞凋亡，采用MTT法、Hoechst法和TUNEL法检测细胞凋亡情况。用PI 3 K/Akt抑制剂LY 294002预处理细胞以研究参与FGF-2保护的可能PI 3 K/Akt途径。免疫印迹法检测p-Akt、p-FoxO 3a和Bim的表达。H2 O2刺激H9 c2细胞后，Akt和FoxO 3a的磷酸化水平降低，FoxO 3a定位于细胞核，细胞凋亡。FGF-2预处理可消除H2 O2的这些作用。此外，FGF-2的保护作用被PI 3 K/Akt抑制剂LY 294002所消除。总之，我们的数据表明，FGF-2通过激活PI 3 K/Akt/FoxO 3a通路保护H2 O2诱导的H9 c2心肌细胞凋亡。
Cardiovascular disease is a growing major global public health problem. Oxidative stress is regarded as one of the key regulators of pathological physiology, which eventually leads to cardiovascular disease. However, mechanisms by which FGF-2 rescues cells from oxidative stress damage in cardiovascular disease is not fully elucidated. Herein this study was designed to investigate the protective effects of FGF-2 in H2O2-induced apoptosis of H9c2 cardiomyocytes, as well as the possible signaling pathway involved. Apoptosis of H9c2 cardiomyocytes was induced by H2O2and assessed using methyl thiazolyl tetrazolium assay, Hoechst, and TUNEL staining. Cells were pretreated with PI3K/Akt inhibitor LY294002 to investigate the possible PI3K/Akt pathways involved in the protection of FGF-2. The levels of p-Akt, p-FoxO3a, and Bim were detected by immunoblotting. Stimulation with H2O2decreased the phosphorylation of Akt and FoxO3a, and induced nuclear localization of FoxO3a and apoptosis of H9c2 cells. These effects of H2O2were abrogated by pretreatment with FGF-2. Furthermore, the protective effects of FGF-2 were abolished by PI3K/Akt inhibitor LY294002. In conclusion, our data suggest that FGF-2 protects against H2O2-induced apoptosis of H9c2 cardiomyocytes via activation of the PI3K/Akt/FoxO3a pathway.