ParkinsonFranceV1, Main, Exploration, bibRecord, 004148

Mitochondrial impairment as an early event in th process of apoptosis induced by glutathione depletion in neuronal cells : Relevance to Parkinson's disease

Identifieur interne : 004148 ( Main/Exploration ); précédent : 004147; suivant : 004149

Mitochondrial impairment as an early event in th process of apoptosis induced by glutathione depletion in neuronal cells : Relevance to Parkinson's disease

Auteurs : M. Merad-Boudia [France] ; A. Nicole [France] ; D. Santiard-Baron [France] ; C. Saille [France] ; I. Ceballos-Picot [France]

Source :

Biochemical pharmacology [ 0006-2952 ] ; 1998.

RBID : Pascal:99-0003529

Descripteurs français

Pascal (Inist)
- Glutathion, Radical libre, Chaîne respiratoire, Parkinson maladie, Neurone, Stress oxydatif, Apoptose, Mort cellulaire, Mitochondrie, In vitro, Antioxydant, Prévention.

English descriptors

KwdEn :
- Animals, Antioxidant, Apoptosis, Apoptosis (physiology), Buthionine Sulfoximine (pharmacology), Cell Line, Cell death, Electron Transport (physiology), Enzyme Inhibitors (pharmacology), Free radical, Glutamate-Cysteine Ligase (antagonists & inhibitors), Glutathione, Glutathione (metabolism), In vitro, Mice, Mitochondria, Mitochondria (physiology), Neuron, Neurons (metabolism), Neurons (pathology), Oxidation-Reduction, Oxidative Stress (physiology), Oxidative stress, Parkinson Disease (metabolism), Parkinson Disease (pathology), Parkinson disease, Prevention, Respiratory chain, Time Factors, Tumor Cells, Cultured.
MESH :
- chemical , antagonists & inhibitors : Glutamate-Cysteine Ligase.
- chemical , metabolism : Glutathione.
- chemical , pharmacology : Buthionine Sulfoximine, Enzyme Inhibitors.
- metabolism : Neurons, Parkinson Disease.
- pathology : Neurons, Parkinson Disease.
- physiology : Apoptosis, Electron Transport, Mitochondria, Oxidative Stress.
- Animals, Cell Line, Mice, Oxidation-Reduction, Time Factors, Tumor Cells, Cultured.

Abstract

In Parkinson's disease (PD), dopaminergic cell death in the substantia nigra was associated with a profound glutathione (GSH) decrease and a mitochondrial dysfunction. The fall in GSH concentration seemed to appear before the mitochondrial impairment and the cellular death, suggesting that a link may exist between these events.The relationships between GSH depletion, reactive oxygen species (ROS) production, mitochondrial dysfunction and the mode of cell death in neuronal cells remain to be resolved and will provide important insights into the etiology of Parkinson's disease. An approach to determine the role of GSH in the mitochondrial function and in neurodegeneration was to create a selective depletion of GSH in a neuronal cell line in culture (NS20Y) by inhibiting its biosynthesis with L-buthionine(S,R)-sulfoximine (BSO), a specific inhibitor of γ-glutamylcysteine synthetase. This treatment led to a nearly complete GSH depletion after 24 hr and induced cellular death via an apoptotic pathway after 5 days of BSO treatment. By using the reactive oxygen species-sensitive probe 2',7'-dichlorofluorescin, we observed that the rapid GSH depletion was accompanied, early in the process, by a strong and transient intracellular increase in reactive oxygen species evidenced after I hr with BSO, culminating after 3 hr when the GSH level decreased to 30% of normal. GSH depletion induced a loss of mitochondrial function after 48 hr of BSO treatment. In particular, the activities of complexes I, II and IV of the respiratory chain were decreased by 32, 70 and 65%, respectively as compared to controls. These results showed the crucial role of GSH for maintaining the integrity of mitochondrial function in neuronal cells. Oxidative stress and mitochondrial impairment, preceding DNA fragmentation, could he early events in the apoptotic process induced by GSH depletion. Our data are consistent with the hypothesis that GSH depletion could contribute to neuronal apoptosis in Parkinson's disease through oxidative stress and mitochondrial dysfunction. BIOCHEM PHARMACOL 56;5: 645-655, 1998.

Affiliations:

Le document en format XML

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<term>Buthionine Sulfoximine (pharmacology)</term>
<term>Cell Line</term>
<term>Cell death</term>
<term>Electron Transport (physiology)</term>
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<term>Parkinson Disease (pathology)</term>
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<front><div type="abstract" xml:lang="en">In Parkinson's disease (PD), dopaminergic cell death in the substantia nigra was associated with a profound glutathione (GSH) decrease and a mitochondrial dysfunction. The fall in GSH concentration seemed to appear before the mitochondrial impairment and the cellular death, suggesting that a link may exist between these events.The relationships between GSH depletion, reactive oxygen species (ROS) production, mitochondrial dysfunction and the mode of cell death in neuronal cells remain to be resolved and will provide important insights into the etiology of Parkinson's disease. An approach to determine the role of GSH in the mitochondrial function and in neurodegeneration was to create a selective depletion of GSH in a neuronal cell line in culture (NS20Y) by inhibiting its biosynthesis with L-buthionine(S,R)-sulfoximine (BSO), a specific inhibitor of γ-glutamylcysteine synthetase. This treatment led to a nearly complete GSH depletion after 24 hr and induced cellular death via an apoptotic pathway after 5 days of BSO treatment. By using the reactive oxygen species-sensitive probe 2',7'-dichlorofluorescin, we observed that the rapid GSH depletion was accompanied, early in the process, by a strong and transient intracellular increase in reactive oxygen species evidenced after I hr with BSO, culminating after 3 hr when the GSH level decreased to 30% of normal. GSH depletion induced a loss of mitochondrial function after 48 hr of BSO treatment. In particular, the activities of complexes I, II and IV of the respiratory chain were decreased by 32, 70 and 65%, respectively as compared to controls. These results showed the crucial role of GSH for maintaining the integrity of mitochondrial function in neuronal cells. Oxidative stress and mitochondrial impairment, preceding DNA fragmentation, could he early events in the apoptotic process induced by GSH depletion. Our data are consistent with the hypothesis that GSH depletion could contribute to neuronal apoptosis in Parkinson's disease through oxidative stress and mitochondrial dysfunction. BIOCHEM PHARMACOL 56;5: 645-655, 1998.</div>
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La maladie de Parkinson en France (serveur d'exploration)

Mitochondrial impairment as an early event in th process of apoptosis induced by glutathione depletion in neuronal cells : Relevance to Parkinson's disease

Mitochondrial impairment as an early event in th process of apoptosis induced by glutathione depletion in neuronal cells : Relevance to Parkinson's disease

Source :

Descripteurs français

English descriptors

Abstract

Links toward previous steps (curation, corpus...)

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri

	La maladie de Parkinson en France (serveur d'exploration)
	Attention, ce site est en cours de développement ! Attention, site généré par des moyens informatiques à partir de corpus bruts. Les informations ne sont donc pas validées.