Objective To study the apoptotic effects of 1 methyl 4 phenyl 1,2,3,6 tetrahydropyridine (MPTP) on the nigral dopaminergic neurons of mice and 1 methyl 4 phenylpyridium ion (MPP +) on pheochromocytoma (P...Objective To study the apoptotic effects of 1 methyl 4 phenyl 1,2,3,6 tetrahydropyridine (MPTP) on the nigral dopaminergic neurons of mice and 1 methyl 4 phenylpyridium ion (MPP +) on pheochromocytoma (PC12) cells, as well as the antagonism of Eldepryl against MPTP's apoptotic effect Methods Three groups of C 57 BL mice were treated with MPTP, Eldepryl plus MPTP and normal saline, respectively, for 7 days before performing TUNEL (terminal deoxyneucleotidyl transferase mediated dUTP x nick end labeling) and FACS (fluorescence activated cell sorting) analyses of neuronal apoptosis in the substantia nigra The same tests were employed in cell culture to examine apoptosis in PC12 cells treated with MPP +, MPTP or PBS Results Intraperitoneal administration of MPTP 30?mg/kg could induce nigral apoptosis, and oral use of Eldepryl prior to MPTP treatment could completely prevent the nigral apoptosis caused by MPTP MPP +, an intermediate metabolite of MPTP, could lead to the apoptosis of PC12 cells, whereas MPTP itself had no such effect on PC12 cells Conclusions The experiment indicated that the neurotoxin, MPTP, might cause the death of nigral neurons through a mechanism of apoptosis and this effect might be mediated by its bioactive intermediate metabolite MPP + Eldepryl could protect the neurotoxicity from MPTP展开更多
Parkinson＇s disease （PD） is a neurodegenerative disease with a long preclinical phase. The continuous loss of dopaminergic （DA） neurons is one of the pathogenic hallmarks of PD. Diagnosis largely depends on clini...Parkinson＇s disease （PD） is a neurodegenerative disease with a long preclinical phase. The continuous loss of dopaminergic （DA） neurons is one of the pathogenic hallmarks of PD. Diagnosis largely depends on clinical observation, but motor dysfunctions do not emerge until 70%-80% of the nigrostriatal nerve terminals have been destroyed. Therefore, a biomarker that indicates the degeneration of DA neurons is urgently needed. Transcrip- tion factors are sequence-specific DNA-binding proteins that regulate RNA synthesis from a DNA template. The precise control of gene expression plays a critical role in the development, maintenance, and survival of cells, including DA neurons. Deficiency of certain transcription factors has been associated with DA neuron loss and PD. In this review, we focus on some transcription factors and discuss their structure, function, mechanisms of neuropro- tection, and their potential for use as biomarkers indicating the degeneration of DA neurons.展开更多
文摘Objective To study the apoptotic effects of 1 methyl 4 phenyl 1,2,3,6 tetrahydropyridine (MPTP) on the nigral dopaminergic neurons of mice and 1 methyl 4 phenylpyridium ion (MPP +) on pheochromocytoma (PC12) cells, as well as the antagonism of Eldepryl against MPTP's apoptotic effect Methods Three groups of C 57 BL mice were treated with MPTP, Eldepryl plus MPTP and normal saline, respectively, for 7 days before performing TUNEL (terminal deoxyneucleotidyl transferase mediated dUTP x nick end labeling) and FACS (fluorescence activated cell sorting) analyses of neuronal apoptosis in the substantia nigra The same tests were employed in cell culture to examine apoptosis in PC12 cells treated with MPP +, MPTP or PBS Results Intraperitoneal administration of MPTP 30?mg/kg could induce nigral apoptosis, and oral use of Eldepryl prior to MPTP treatment could completely prevent the nigral apoptosis caused by MPTP MPP +, an intermediate metabolite of MPTP, could lead to the apoptosis of PC12 cells, whereas MPTP itself had no such effect on PC12 cells Conclusions The experiment indicated that the neurotoxin, MPTP, might cause the death of nigral neurons through a mechanism of apoptosis and this effect might be mediated by its bioactive intermediate metabolite MPP + Eldepryl could protect the neurotoxicity from MPTP
基金supported by the National Key Research and Development Program of China (2016YFC1306603)the National Natural Science Foundation of China (31671060)
文摘Parkinson＇s disease （PD） is a neurodegenerative disease with a long preclinical phase. The continuous loss of dopaminergic （DA） neurons is one of the pathogenic hallmarks of PD. Diagnosis largely depends on clinical observation, but motor dysfunctions do not emerge until 70%-80% of the nigrostriatal nerve terminals have been destroyed. Therefore, a biomarker that indicates the degeneration of DA neurons is urgently needed. Transcrip- tion factors are sequence-specific DNA-binding proteins that regulate RNA synthesis from a DNA template. The precise control of gene expression plays a critical role in the development, maintenance, and survival of cells, including DA neurons. Deficiency of certain transcription factors has been associated with DA neuron loss and PD. In this review, we focus on some transcription factors and discuss their structure, function, mechanisms of neuropro- tection, and their potential for use as biomarkers indicating the degeneration of DA neurons.
