Effects of MPTP on apoptosis of mouse dopaminergic neuron MN9D cells
Aim:To investigate the effects of MPTP on apoptosis of mouse dopaminergic neuron MN9D cells and its possible mechanism.Methods:MN9D cells were treated with 0 or 1 μmol/L MPTP(control group and MPTP group),or transfected with pcDNA4 or pcDNA4-BACE2(control group and BACE2 group),respectively.Western blot was used to de-tect the expressions of BACE2,Cleaved Caspase-3 and endogenous DSG2 proteins.MN9D cells were allocated into DSG2 group,DSG2 +BACE2 group and DSG2 +BACE2 +BACE inhibitor group,and cells were transfected with pENTER-DSG2 + pcDNA4,pENTER-DSG2 +pcDNA4-BACE2,and pENTER-DSG2 +pcDNA4-BACE2 and treated with 1 μmol/L BACE in-hibitor,respectively.Western blot was used to detect the expressions of full-length DSG2 and DSG2 fragments.Results:Compared with control group,the expressions of BACE2 and Cleaved Caspase-3 in MPTP group were increased(P<0.05).Compared with control group,the expression of Cleaved Caspase-3 in BACE2 group overexpressing BACE2 was increased,and that of endogenous DSG2 reduced(P<0.05).Compared with DSG2 group,the expression of full-length DSG2 de-creased,and the carboxyl terminal fragment and the amino terminal fragment of extracellular DSG2 in DSG2 +BACE2 group increased(P<0.05).The expressions of full-length DSG2 and DSG2 fragments in DSG2 +BACE2 +BACE inhibitor group were similar to those in DSG2 group(P>0.05).Conclusion:MPTP could promote apoptosis by up-regulating BACE2,which might be laid to BACE2's cutting DSG2;BACE2 and DSG2 may be involved in the pathogenesis of Parkinson's disease.
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