Preliminary Study On Protection Mechanisms Of FGF2 Against ERS Induced-apoptosis In Cerebellar Granule Neurons

Endoplasmic reticulum stress (ERS) is caused by disturbances in the structure and function of the endoplasmic reticulum(ER) with the accumulation of misfolded proteins and alterations in the calcium homeostasis. The ERS response is characterized by changes in specific proteins, causing translational attenuation, expression of ER chaperones and degradation of misfolded proteins.In case of prolonged or aggravated ERS, cellular signals leading to cell death are activated.ERS induced cell apoptosis may be reasons of some neurodegenerative diseases,so studies about this field attract more and more attention. Tunicamycin, which can induce ERS was apploied to many models of cell apoptosis.Basic fibroblast growth factor (FGF2) can regulate cell migration, proliferation and apoptosis.Recent research has demonstrated that FGF2 have anti-apoptotic action in several different cell types, but it aslo have pro-apoptotic action in different developing phases and cell types.In this paper, studies have been conducted to elucidate the effectiveness of FGF2 to tunicamycin-induced ERS triggered cell apoptosis in cerebellar granule neurons (CGN).As a result,we learnd that:(1)When treated CGN with tunicamycin, neuronal apoptosis were increased , while FGF2 reduced Tunicamycin-induced cell apoptosis in CGN;(2) When treated CGN with tunicamycin, ERK1/2 , AKT were inactivated and JNK was activated;(3) When treated CGN with FGF2,an opposite result appears that ERK1/2 , AKT were activated and JNK was inactivated;(4) FGF2 activated AKT and ERK1/2, inactivate JNK in tunicamycin-induced CGN;(5)Followed these, when administer inhibitors of ERK1/2 pathway, JNK pathway ,AKT pathway,finded that the inhibition of ERK1/2 pathway and JNK pathway almost did not change apoptosis but the inhibition of AKT pathway caused the absence of the neuroprotection of FGF2 in tunicamycin-induced CGN.These results indicate that FGF2 protect neuronal cell against tunicamycin induced neuronal apoptosis through PI3K/AKT pathway.In a brief, our study has confirmed that FGF2 activate AKT and ERK1/2, inactivate JNK in tunicamycin-induced CGN,and markedly reduced tunicamycin-induced cell apoptosis in CGN through PI3K/AKT pathway.These results may be usable in the next more studies about the signal mechanism of neuroprotection of FGF2 against tunicamycin-induced apoptosis in CGN, provide insights that may be applicable to studies in apoptosis of other cell type and other inductors's effects , and help us to realize more about the signal transduction mechanism of FGF2's anti-apoptotic action.