α-lipoic acid protects dopaminergic neurons against MPP+-induced apoptosis by attenuating reactive oxygen species formation
| Autor: | Lin-Sen Hu, Guang-Ren Li, Yan Lu, Ming Yao, Ming Chang, Wei Cheng, Da-Wei Li, Zhi-Qiang Liu |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Programmed cell death
1-Methyl-4-phenylpyridinium Cell Survival Apoptosis Mitochondrion Biology medicine.disease_cause PC12 Cells chemistry.chemical_compound Genetics medicine Animals bcl-2-Associated X Protein chemistry.chemical_classification Membrane Potential Mitochondrial Reactive oxygen species Thioctic Acid Caspase 3 MPTP Dopaminergic Neurons Dopaminergic Neurodegeneration General Medicine medicine.disease Cell biology Rats Neuroprotective Agents chemistry Proto-Oncogene Proteins c-bcl-2 Reactive Oxygen Species Oxidative stress |
| Zdroj: | International journal of molecular medicine. 32(1) |
| ISSN: | 1791-244X |
| Popis: | Reactive oxygen species (ROS) elicited by oxidative stress are widely recognized as a major initiator in the dege-neration of dopaminergic neurons distinctive of Parkinson's disease (PD). The interaction of ROS with mitochondria triggers sequential events in the mitochondrial cell death pathway, which is thought to be responsible for ROS-mediated neurodegeneration in PD. α-lipoic acid (LA) is a pleiotropic compound with potential pharmacotherapeutic value against a range of pathophysiological insults. Its protective actions against oxidative damage by scavenging ROS and reducing production of free radicals have been reported in various in vitro and in vivo systems. This study analyzed the ability of LA to protect PC12 neuronal cells from toxicity of 1-methyl-4-phenylpyridinium (MPP+), the neurotoxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) which is known to kill dopaminergic neurons selectively and to cause severe parkinsonism-like symptoms in humans and primate animals. Our results demonstrate that the apoptosis of PC12 cells elicited by MPP+ could be significantly prevented by pretreatment with LA for 1 h. In addition, LA inhibits intercellular ROS levels and the mitochondrial transmembrane permeability, the key players in the pathogenesis of PD, thereby protecting dopaminergic neuronal cells against oxidative damage. |
| Databáze: | OpenAIRE |
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