Atorvastatin Inhibits Hypoxia-induced Endoplasmic Reticulum Stress In Neural Stem Cells

Objective : Using hypoxia incubator to establish hypoxic model of neural stem cells(NSC),Studying whether atorvastatin(ATV)inhibits hypoxia–induced endoplasmic reticulum stress(ERS)in NSCs,and the effect of ATV on PERK-e IF2 pathway in ERS.Methods: 1.According to different hypoxic time divided into hypoxic 0h group,3h group,6h group,12 h group,24 h group,Lactate dehydrogenase(LDH)kit colorimetric assay NSCs function,the expression of GRP78,PERK,e IF2? determined by western blotting.To observe whether hypoxia can affect the metabolism of NSCs and induced ERS,and chose the time when the ERS expression strongest and cell function injured most significant.2.According to previous results,Experiments are divided into normal group,hypoxic group,normal+ATV group,hypoxic+ATV group,normal+Sal group,hypoxic+Sal group,respectively cultured 12 h,LDH kit colorimetric assay NSCs function,Western-Blot detection of ERS-related proteins GRP78,PERK,e IF2? expression.Observing whether ATV inhibits hypoxia-induced ERS in NSCs,and its possible mechanism.Results: 1.With the extension of hypoxic time,LDH release increase,showed a significant increase at hypoxic 12 h and statistically different(P<0.001);With the extension of hypoxic time,Western-Blot detection of GRP78,PERK,e IF2? expression all increase,showed a significant increase at hypoxic 12 h and statistically different(P<0.001).Confirming that hypoxia can induce ERS and metabolic function in the NSCs.2.Compared with the normal group,hypoxic group LDH release increased(p <0.001),compared with hypoxic group,hypoxic+ATV group,hypoxic+Sal group LDH release decreased(p<0.001),compared with normal group,hypoxic+ATV group and the hypoxic+Sal group have no significant difference in the release of LDH(P>0.05).Compared with the normal group,the expression of ERS-related proteins GRP78,PERK,e IF2? in hypoxic group increased(P<0.001);Compared with the hypoxic group,ERS-related proteins GRP78,PERK,e IF2? in the hypoxic+ATV group expression is reduced(P<0.001);Compared with the hypoxic group,e IF2? expression decreased in hypoxic+Sal Group(P<0.001),but have no significant difference in expression of GRP78,PERK(P>0.05);The expression of ERS-related proteins have no significant difference in normal group,normal +ATV group and normal +Sal group(P>0.05).Conclusions: 1?Hypoxia may induced ERS in NSCs,and influenced the cell metabolism function.2?ATV inhibits hypoxia-induced endoplasmic reticulum stress in neural stem cells,one of the mechanism may achieve through downergulation PERK-e IF2? pathway.