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Regulatory Role of HIF-1α in the SH-SY5Y Cells Excitotoxic Injury
Li Yongjin, Yang Kaiyong, Kan Meijia, Huang He, Zhang Yi, Chen Yuefang, Duan Lirong, Huang Xiaojia*
School of Medicine, Jiangsu University, Zhenjiang 212013, China
Abstract: To investigate the role of HIF-1α in SH-SY5Y cell injury induced by quinolinic acid， SH-SY5Y cells were divided into control group， quinolinic acid low， medium and high dosage groups and HIF-1α inhibitor (2ME2) pretreated group; the cell viability was determined by MTT reduction assay and LDH assay; cell apoptosis was determined by Hoechst 33342 staining; the intracellular distribution of HIF-1α was examined by HIF-1α immunostaining and the expressions of HIF-1α， Akt， p-Akt， Bcl-2 and Bax were determined by Western blot. The results showed that quinolinic acid induced SH-SY5Y cell damage in a dosage- and time-dependent manner， leading to apoptosis. In addition， quinolinic acid enhanced HIF-1α expression and nuclear translocation. The p-Akt expression and Bax/Bcl-2 ratio were increased by quinolinc acid in SH-SY5Y cells， and 2ME2 inhibited quinolinicacid induced SH-SY5Y cells damage and reduced the expression of HIF-1α， p-Akt and Bax/Bcl-2. These results indicated that HIF-1α/Akt pathway mediates quinolinic acid induced cell apoptosis in SH-SY5Y cells， and HIF-1α inhibitor (2ME2) can lower the degree of SH-SY5Y cells damage induced by quinolinic acid， reducing apoptosis.
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