Mutant alpha-synuclein and autophagy in PC12 cells

来源 :Neural Regeneration Research | 被引量 : 0次 | 上传用户:s83436776
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Several studies have demonstrated that overexpression of mutant α-synuclein in PC12 cells is related to occurrence of autophagy.The present study established mutant α-synuclein(A30P)-transfected PC12 cells and treated them with the autophagy inducer rapamycin and autophagy inhibitor wortmannin,respectively.Results demonstrated that mutantα-synuclein resulted in cell death via autophagy and involved α-synuclein accumulation,membrane lipid oxidation,and loss of plasma membrane integrity.Mutant α-synuclein(A30P)also mediated toxicity of 1-methyl-4-phenylpyridinium ion.Moreover,rapamycin inhibited α-synuclein aggregation,while wortmannin promoted α-synuclein aggregation and cell death.To further determine the role of autophagy due to mutant α-synuclein,the present study measured expression of microtubule-associated protein light chain 3.Results revealed that wortmannin and 1-methyl-4-phenylpyridinium ion inhibited expression of microtubule-associated protein light chain 3,while rapamycin promoted its expression.These findings suggested that abnormal aggregation of α-synuclein induced autophagic programmed cell death in PC12 cells. Several studies have demonstrated that overexpression of mutant α-synuclein in PC12 cells is related to the occurrence of autophagy. The present study establishes mutant α-synuclein (A30P) -transfected PC12 cells and treated them with the autophagy inducer rapamycin and autophagy inhibitor wortmannin, respectively . Results of that mutant α-synuclein resulted in cell death via autophagy and involved in α-synuclein accumulation, membrane lipid oxidation, and loss of plasma membrane integrity. Mutant α-synuclein (A30P) also mediated toxicity of 1-methyl-4-phenylpyridinium ion . Moreover, rapamycin inhibited α-synuclein aggregation, while wortmannin promoted α-synuclein aggregation and cell death. To further determine the role of autophagy due to mutant α-synuclein, the present study measured expression of microtubule-associated protein light chain 3. Results revealed that wortmannin and 1-methyl-4-phenylpyridinium ion inhibited expression of microtubule-associated protein light chain 3, while rap amycin promoted its expression. thisse findings suggests that abnormal aggregation of a-synuclein induced autophagic programmed cell death in PC12 cells.
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