ParkinsonFranceV1, Main, Exploration, bibRecordById, Pascal:99-0512880

Overproduction of Cu/Zn-superoxide dismutase or Bcl-2 prevents the brain mitochondrial respiratory dysfunction induced by glutathione depletion

Identifieur interne : 003E93 ( Main/Exploration ); précédent : 003E92; suivant : 003E94

Overproduction of Cu/Zn-superoxide dismutase or Bcl-2 prevents the brain mitochondrial respiratory dysfunction induced by glutathione depletion

Auteurs : M. Merad-Saïdoune [France] ; E. Boitier [France] ; A. Nicole [France] ; C. Marsac [France] ; J. C. Martinou [Suisse] ; B. Sola [France] ; P.-M. Sinet [France] ; I. Ceballos-Picot [France]

Source :

Experimental neurology [ 0014-4886 ] ; 1999.

RBID : Pascal:99-0512880

Descripteurs français

Pascal (Inist)
- Superoxide dismutase, Déplétion, Glutathion, Chaîne respiratoire, Mitochondrie, Stress oxydatif, Parkinson maladie, Pathogénie, Modèle animal, Animal transgénique, Souris.
Wicri :
- topic : Animal transgénique.

English descriptors

KwdEn :
- Animal model, Depletion, Glutathione, Mitochondria, Mouse, Oxidative stress, Parkinson disease, Pathogenesis, Respiratory chain, Superoxide dismutase, Transgenic animal.

Abstract

Recent work has focused attention on the role of oxidative stress in various acute and chronic neurodegenerative diseases. Low concentrations of the powerful antioxidant glutathione (GSH) and impaired brain energy metabolism, particularly in the substantia nigra, are key features of Parkinson's disease (PD). The main goal of this study was to better characterize the deleterious effects of brain GSH depletion on mitochondrial function. We depleted GSH in the brains of newborn wild-type (WT) and transgenic (Tg) mice overproducing either human Cu/Zn-superoxide dismutase (h-CuZnSOD) or human Bcl2 (h-Bcl-2), by subcutaneous injection of L-buthionine sulfoximine (BSO), a specific inhibitor of γ-glutamylcysteine synthetase. GSH was 97% depleted in brain homogenates and 90% depleted in brain mitochondria for both WT and Tg mice. This depletion of brain GSH led to a decrease in the activity of the GSH-dependent antioxidant enzyme glutathione peroxidase, both in WT and in Tg animals. BSO treatment decreased the activities of respiratory complexes I, II, and IV in the brain homogenates of WT mice. BSO-treated h-CuZnSOD or h-Bcl-2 Tg mice had no respiratory chain deficiencies. Thus, brain GSH depletion leads to the impairment of mitochondrial respiratory chain activity. The protection of mitochondrial respiratory function by overproduction of Bcl-2 may result from a decrease in the generation of reactive oxygen species (ROS) or lipid peroxidation. The protection of mitochondria by overproduction of CuZn-SOD is consistent with the involvement of superoxide or superoxide-derived ROS in the mitochondrial dysfunction caused by brain GSH depletion. This study demonstrates that the antioxidant balance is critical for maintenance of brain mitochondrial function, and its disruption may contribute to the pathogenesis of PD.

Affiliations:

France, Suisse
Basse-Normandie, Région Normandie, Île-de-France
Caen, Paris

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Le document en format XML

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<term>Depletion</term>
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<term>Oxidative stress</term>
<term>Parkinson disease</term>
<term>Pathogenesis</term>
<term>Respiratory chain</term>
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<term>Déplétion</term>
<term>Glutathion</term>
<term>Chaîne respiratoire</term>
<term>Mitochondrie</term>
<term>Stress oxydatif</term>
<term>Parkinson maladie</term>
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<term>Modèle animal</term>
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<front><div type="abstract" xml:lang="en">Recent work has focused attention on the role of oxidative stress in various acute and chronic neurodegenerative diseases. Low concentrations of the powerful antioxidant glutathione (GSH) and impaired brain energy metabolism, particularly in the substantia nigra, are key features of Parkinson's disease (PD). The main goal of this study was to better characterize the deleterious effects of brain GSH depletion on mitochondrial function. We depleted GSH in the brains of newborn wild-type (WT) and transgenic (Tg) mice overproducing either human Cu/Zn-superoxide dismutase (h-CuZnSOD) or human Bcl2 (h-Bcl-2), by subcutaneous injection of L-buthionine sulfoximine (BSO), a specific inhibitor of γ-glutamylcysteine synthetase. GSH was 97% depleted in brain homogenates and 90% depleted in brain mitochondria for both WT and Tg mice. This depletion of brain GSH led to a decrease in the activity of the GSH-dependent antioxidant enzyme glutathione peroxidase, both in WT and in Tg animals. BSO treatment decreased the activities of respiratory complexes I, II, and IV in the brain homogenates of WT mice. BSO-treated h-CuZnSOD or h-Bcl-2 Tg mice had no respiratory chain deficiencies. Thus, brain GSH depletion leads to the impairment of mitochondrial respiratory chain activity. The protection of mitochondrial respiratory function by overproduction of Bcl-2 may result from a decrease in the generation of reactive oxygen species (ROS) or lipid peroxidation. The protection of mitochondria by overproduction of CuZn-SOD is consistent with the involvement of superoxide or superoxide-derived ROS in the mitochondrial dysfunction caused by brain GSH depletion. This study demonstrates that the antioxidant balance is critical for maintenance of brain mitochondrial function, and its disruption may contribute to the pathogenesis of PD.</div>
</front>
</TEI>
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	La maladie de Parkinson en France (serveur d'exploration)
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La maladie de Parkinson en France (serveur d'exploration)

Overproduction of Cu/Zn-superoxide dismutase or Bcl-2 prevents the brain mitochondrial respiratory dysfunction induced by glutathione depletion

Overproduction of Cu/Zn-superoxide dismutase or Bcl-2 prevents the brain mitochondrial respiratory dysfunction induced by glutathione depletion

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