PI3K/Akt/FoxO3a signaling mediates cardioprotection of FGF-2 against hydrogen peroxide-induced apoptosis in H9c2 cells

Abstract

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 H2O2 and 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 H2O2 decreased the phosphorylation of Akt and FoxO3a, and induced nuclear localization of FoxO3a and apoptosis of H9c2 cells. These effects of H2O2 were 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.

FGF-2 Transcriptionally Down-Regulates the Expression of BNIP3L via PI3K/Akt/FoxO3a Signaling and Inhibits Necrosis and Mitochondrial Dysfunction Induced by High Concentrations of Hydrogen Peroxide in H9c2 Cells

“…Several studies suggest that the protective effects of FGF-2 are mediated by PKC and MAPK activation [27]. Moreover, the PI3K/AKT pathway, which is independent of the PKC, PKA, and MAPK signaling pathways [28,29], is activated by FGF-2 and prevents ROS-induced apoptosis in H9c2 cells through the Forkhead box O3 (FoxO3a) transcription factor [30]. The FoxO3a transcription factor is one of the most important downstream targets of PI3K/Akt signaling and a crucial regulator of apoptosis [18,[31][32][33].…”

Sprouty2 is involved in the control of osteoblast proliferation and differentiation through the FGF and BMP signaling pathways

“…On the other hand, it has been known that Phosphoinositide 3‐kinase (PI3K)‐Akt pathway is also associated with FGF signal and Sprouty2 in cell proliferation and survival (Ornitz and Itoh, ; Zhang et al, ; Liu et al, ). Therefore, to examine the influence of Sprouty2 on PI3K‐Akt pathway in MC3T3‐E1 cells, we investigated the phosphorylation of Akt in the same way as for ERK1/2 phosphorylation.…”

“…Statistically significant differences were determined by the Mann-Whitney U-test ( * P < 0.05). (Ornitz and Itoh, 2015;Zhang et al, 2015;Liu et al, 2016). Therefore, to examine the influence of Sprouty2 on PI3K-Akt pathway in MC3T3-E1 cells, we investigated the phosphorylation of Akt in the same way as for ERK1/2 phosphorylation.…”

Dihydromyricetin protects HUVECs of oxidative damage induced by sodium nitroprusside through activating PI3K/Akt/FoxO3a signalling pathway

“…Here, we focus on the PI3k/Akt/FoxO3a pathway, which plays crucial role in promoting survival and function of cardiomyocyte. The previous studies have shown that hydrogen peroxide induces cardiomyocyte apoptosis by inhibiting the PI3K/Akt pathway . The PI3K/Akt pathway has shown related to the human atherosclerosis .…”

“…The previous studies have shown that hydrogen peroxide induces cardiomyocyte apoptosis by inhibiting the PI3K/Akt pathway. 33 The PI3K/Akt pathway has shown related to the human atherosclerosis. 34 FoxO3a is an important downstream target of the PI3K/Akt pathway, which was mainly regulated by Akt.…”