Fibroblast growth factor-8 inhibits oxidative stress-induced apoptosis in H9c2 cells.
Fibroblast growth factors (FGFs) comprise a large family of signaling molecules that involve cell patterning, mobilization, differentiation, and proliferation. Various FGFs, including FGF-1, FGF-2, and FGF-5, have been shown to play a role in cytoprotection during adverse cardiac events; however, whether FGF-8 is a cytoprotective remains unclear. The current study was designed to evaluate the effect of FGF-8 treatment on oxidative stress-induced apoptosis in H9c2 cells. Cells were divided into three groups: control, H2O2(400 µm H2O2), and H2O2+ FGF-8 (4 ng/ml FGF-8). Our results suggest apoptosis was significantly (p < 0.05) enhanced in the H2O2group relative to control. Moreover, a significant (p < 0.05) decline in apoptosis was observed in the H2O2+ FGF-8 group compared to H2O2-treated cells as evidenced by TUNEL staining, a cell death detection ELISA, and cell viability. Levels of downstream apoptotic mediators, caspase-3 and caspase-9, were significantly (p < 0.05) upregulated following H2O2treatment but were abrogated following FGF-8 application. Expression levels of Forkhead box protein O1 (FoxO-1), MnSOD, catalase, pAKT, and p-mTOR were significantly (p < 0.05) reduced in the H2O2group (p < 0.05). Notably, these levels were significantly (p < 0.05) reversed following FGF-8 treatment. Our data, for the first time, suggest FGF-8 is an anti-apoptotic mediator in oxidative-stressed H9c2 cells. Furthermore, our data demonstrate that apoptotic inhibition by FGF-8 is consequent to FoxO-1 oxidative detoxification as well as augmentation to the PI3K/AKT cell survival pathway.
Division of Metabolic and Cardiovascular Sciences, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, 32816, USA.
Reetu D
RD
Singla
Division of Metabolic and Cardiovascular Sciences, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, 32816, USA.
Jing
J
Wang
Division of Metabolic and Cardiovascular Sciences, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, 32816, USA. dsingla@ucf.edu.|Division of Metabolic and Cardiovascular Sciences, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, 4000 Central Florida Blvd, Room 224, Orlando, FL, 32816, USA. dsingla@ucf.edu.
Dinender K
DK
Singla
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D051524:Fibroblast Growth Factor 8 / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D018384:Oxidative Stress / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D000071161:Forkhead Box Protein O1
D051524:Fibroblast Growth Factor 8; D006861:Hydrogen Peroxide; D009419:Nerve Tissue Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C496458:Fgf8 protein, rat; C074639:Foxo1 protein, rat; D000071161:Forkhead Box Protein O1
AKT; Apoptosis; FGF-8; FoxO-1; H9c2 cardiomyoblasts