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19 April 2017 : Laboratory Research  

Insulin Growth Factor 1 Protects Neural Stem Cells Against Apoptosis Induced by Hypoxia Through Akt/Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase (Akt/MAPK/ERK) Pathway in Hypoxia-Ishchemic Encephalopathy

Bing Zhao1BCEF, Zebao Zheng1ADEF*

DOI: 10.12659/MSM.901055

Med Sci Monit 2017; 23:1872-1879

Abstract

BACKGROUND: Insulin growth factor 1 (IGF-1) is reported to modulate cell growth and acts as potential therapy for traumatic brain injury. This study was designed to investigate the effect of IGF-1 on hypoxia-induced apoptosis in neural stem cells (NSCs).

MATERIAL AND METHODS: A hypoxia model was constructed using NSCs separated from the hippocampus of rat. NSCs were divided into four groups: cells under normoxic conditions that acted as controls (C group), cells under hypoxia (H group), cells under hypoxia with IGF-1 (HI group), and cells under hypoxia with IGF-1 as well as picropodophyllin (PPP), which acts as an inhibitor of the IGF-1 receptor (HIP group). The cell viability and apoptosis were respectively measured by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and flow cytometry. Finally, the phosphorylation levels of apoptosis-associated proteins and key kinases in the phosphatidylinositol-3-kinase (PI3K)/AKT and the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathways were detected by Western blot analysis.

RESULTS: In comparison with the H group, the cell viability was increased while the cell apoptosis was reduced by IGF-1 in the HI group. Besides, the expression levels of Bax, cytochrome c, and activated caspase-3 were all improved in the H group, and the remarkable differences were eliminated in the HI group compared with the C group. The expression level of Bcl-2 was the opposite. Additionally, down-regulations of phosphorylated AKT, MAPK, and ERK induced by hypoxia were all improved by IGF-1. All the influences of IGF-1 were weakened by addition of PPP.

CONCLUSIONS: IGF-1 increased cell viability while decreasing apoptosis in hypoxic NSCs through the PI3K/AKT and MAPK/ERK pathways.

Keywords: Insulin-Like Growth Factor Binding Protein 1, MAP kinases, neural stem cells, Phosphatidylinositol 3-Kinases

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750