Neuroprotective effect of asymmetrical dimethylarginine against 1-methyl-4-phenylpyridinium ion-induced damage in PC12 cells

【作者】 李玉娟； 唐小卿；

【机构】 南华大学医学院生理学教研室；

【摘要】 <正>Asymmetric dimethylarginine(ADMA) is a well-known endogenous nitric oxide synthase(NOS) inhibitor. Although it has been shown to be a novel risk marker in cardiovascular medicine and chronic kidney disease,we speculated that in some states associated with excess of nitric oxide(NO),such as l-methyl-4-phenylpyridinium ion(MPP~+)- induced neuronal injury ADMA may be protective by limiting toxic effect of high concentrations of NO.The aim of present study is to explore the neuroprotection of ADMA against MPP~+-induced apoptosis and the molecular mechanisms underlying in PC12 cells.We found that exogenous application of ADMA obviously protected PC12 cells against MPP~+- induced cytotoxicity and apoptosis not only by reducing the loss of mitochondrial membrane potential(MMP),but also by attenuating an increase in intracellular reactive oxygen species(ROS).Moreover,ADMA attenuated MPP~+-induced excessive activation of nitric oxide synthase(NOS) and overproduction of NO.The results of present study suggest that the neuroprotection caused by ADMA is related to preserve MMP and attenuates the MPP~+-induced intracellular ROS generation through inhibiting NOS activity and limiting NO generation.These findings for the first demonstrate that ADMA may be a new therapeutic approach to excess of NO-based neurodegenerative diseases,such as Parkinson’s disease(PD).更多还原

【Abstract】 Asymmetric dimethylarginine(ADMA) is a well-known endogenous nitric oxide synthase(NOS) inhibitor. Although it has been shown to be a novel risk marker in cardiovascular medicine and chronic kidney disease,we speculated that in some states associated with excess of nitric oxide(NO),such as l-methyl-4-phenylpyridinium ion(MPP~+)- induced neuronal injury ADMA may be protective by limiting toxic effect of high concentrations of NO.The aim of present study is to explore the neuroprotection of ADMA against MPP~+-induced apoptosis and the molecular mechanisms underlying in PC12 cells.We found that exogenous application of ADMA obviously protected PC12 cells against MPP~+- induced cytotoxicity and apoptosis not only by reducing the loss of mitochondrial membrane potential(MMP),but also by attenuating an increase in intracellular reactive oxygen species(ROS).Moreover,ADMA attenuated MPP~+-induced excessive activation of nitric oxide synthase(NOS) and overproduction of NO.The results of present study suggest that the neuroprotection caused by ADMA is related to preserve MMP and attenuates the MPP~+-induced intracellular ROS generation through inhibiting NOS activity and limiting NO generation.These findings for the first demonstrate that ADMA may be a new therapeutic approach to excess of NO-based neurodegenerative diseases,such as Parkinson’s disease(PD).更多还原