Influence Of Caveolin-1 On The Autophagy Induced By Glucose Deprivation In PC12 Cells

Glucose deprivation(GD)is a common phenomenon of cellular damage,which is associated with ischemic and anoxic-injury.More and more researcher focus on the molecular mechanism of cellular injury induced by GD.GD is one of the major consequences of ischemia that subsequently induces neuronal cell death.Certainly,Autophagy is a common physiological process of self-renewing cells,and it will be activated when cells affected by glucose deprivation,but excessive autophagy may induce its apoptosis and death.Caveolin-1 is a scaffolding/regulatory protein localized in plasmalemmal caveolae that modulates signaling proteins in diverse mammalian cells,including endothelial cells and adipocytes.We have found that caveolin-1 involved in the apoptosis and GD-induced injury in nerve cells,but the mechanism remains unclear.Recent findings have showed that caveolin-1 also involved in the formation of autophagosome and the expression of many autophagy-related proteins.Thus,we speculate that the protection of caveolin-1 in GD-induced injury may be associated with autophagy in nerve cells.Here,PC12 cells and PC12-Cav-1-KD cells were used in this study.Cell vitality and related protein were respectively tested by flow cytometry and laser confocal.The function of autophagy induced by glucose deprivation in cells was analyzed by MTT,plasmid transfection,Western blot methods.Finally,the role of AKT/m TOR signaling pathways activated by autophagy and the relationship with caveolin-1 in glucose deprivation were detected by Western blot.The aim in this study is to provide powerful experimental basis for clinical ischemia therapy and therapeutic targets.Results:(1)Caveolin-1 and glucose transporter 4(Glut-4)were upregulated by glucose deprivation stress.Cell viability and mitochondrial membrane potential were decreased(p< 0.01),while intracellular calcium ion concentration was increased(p< 0.01)after glucose deprivation in these two cells;Knockdown of Caveolin-1 promoted these changes(p < 0.05).(2)Glucose deprivation after joining autophagy inhibitor 3-MA,cell vitality was reduced(p < 0.01),the expression of Caspase-3 and acid hydrolysis enzyme activity were increased in PC12 cells,but there was no significant change in PC12-Cav-1-KD cells.Glucose deprivation induced autophagy was suppressed using si RNA technology or M-?-CD.While rescue the ecpression of Caveolin-1 could activate autophagy.(3)Akt/m TOR signal pathway was activated by glucose deprivation PC12 cells(p<0.01),but it was significantly educed in PC12-Cav-1-KD cells.After using LY294002 inhibition of PI3 K pathway,we found that Akt/m TOR signaling was by glucose deprivation,and autophagy was inhibited at the same time.Conclusions: Cavolin-1 involved in autophagy induced by glucose deprivation through activating PI3K/Akt/m TOR signaling pathway in PC12 cells.