Overproduction of Cu/Zn-superoxide dismutase or Bcl-2 prevents the brain mitochondrial respiratory dysfunction induced by glutathione depletion
Identifieur interne : 001451 ( PascalFrancis/Corpus ); précédent : 001450; suivant : 001452Overproduction of Cu/Zn-superoxide dismutase or Bcl-2 prevents the brain mitochondrial respiratory dysfunction induced by glutathione depletion
Auteurs : M. Merad-Saïdoune ; E. Boitier ; A. Nicole ; C. Marsac ; J. C. Martinou ; B. Sola ; P.-M. Sinet ; I. Ceballos-PicotSource :
- Experimental neurology [ 0014-4886 ] ; 1999.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
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.
Notice en format standard (ISO 2709)
Pour connaître la documentation sur le format Inist Standard.
| pA |
|
|---|
Format Inist (serveur)
| NO : | PASCAL 99-0512880 INIST |
|---|---|
| ET : | Overproduction of Cu/Zn-superoxide dismutase or Bcl-2 prevents the brain mitochondrial respiratory dysfunction induced by glutathione depletion |
| AU : | MERAD-SAÏDOUNE (M.); BOITIER (E.); NICOLE (A.); MARSAC (C.); MARTINOU (J. C.); SOLA (B.); SINET (P.-M.); CEBALLOS-PICOT (I.) |
| AF : | CNRS URA 1335, Faculté de Médecine Necker Enfants-Malades, Université Paris V, 156 rue de Vaugirard/75730 Paris/France (1 aut., 3 aut., 7 aut., 8 aut.); INSERM U75, Faculté de Médecine Necker Enfants-Malades, Université Paris V, 156 rue de Vaugirard/75730 Paris/France (2 aut., 4 aut.); Serono Pharmaceutical Research Institute, 14 chemin des Aulx, 1228 Plan les Ouates/Geneva/Suisse (5 aut.); Faculté de Médecine, UPRES-EA 2128, CHU Cote de Nacre/14033 Caen/France (6 aut.) |
| DT : | Publication en série; Niveau analytique |
| SO : | Experimental neurology; ISSN 0014-4886; Coden EXNEAC; Etats-Unis; Da. 1999; Vol. 158; No. 2; Pp. 428-436; Bibl. 67 ref. |
| LA : | Anglais |
| EA : | 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. |
| CC : | 002B17G |
| FD : | Superoxide dismutase; Déplétion; Glutathion; Chaîne respiratoire; Mitochondrie; Stress oxydatif; Parkinson maladie; Pathogénie; Modèle animal; Animal transgénique; Souris |
| FG : | Oxidoreductases; Enzyme; Rodentia; Mammalia; Vertebrata; Système nerveux pathologie; Système nerveux central pathologie; Encéphale pathologie; Extrapyramidal syndrome; Maladie dégénérative |
| ED : | Superoxide dismutase; Depletion; Glutathione; Respiratory chain; Mitochondria; Oxidative stress; Parkinson disease; Pathogenesis; Animal model; Transgenic animal; Mouse |
| EG : | Oxidoreductases; Enzyme; Rodentia; Mammalia; Vertebrata; Nervous system diseases; Central nervous system disease; Cerebral disorder; Extrapyramidal syndrome; Degenerative disease |
| SD : | Superoxide dismutase; Depleción; Glutatión; Cadena respiratoria; Mitocondria; Stress oxidativo; Parkinson enfermedad; Patogenia; Modelo animal; Animal transgénico; Ratón |
| LO : | INIST-9181.354000089404550150 |
| ID : | 99-0512880 |
Links to Exploration step
Pascal:99-0512880Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">Overproduction of Cu/Zn-superoxide dismutase or Bcl-2 prevents the brain mitochondrial respiratory dysfunction induced by glutathione depletion</title><author><name sortKey="Merad Saidoune, M" sort="Merad Saidoune, M" uniqKey="Merad Saidoune M" first="M." last="Merad-Saïdoune">M. Merad-Saïdoune</name><affiliation><inist:fA14 i1="01"><s1>CNRS URA 1335, Faculté de Médecine Necker Enfants-Malades, Université Paris V, 156 rue de Vaugirard</s1><s2>75730 Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Boitier, E" sort="Boitier, E" uniqKey="Boitier E" first="E." last="Boitier">E. Boitier</name><affiliation><inist:fA14 i1="02"><s1>INSERM U75, Faculté de Médecine Necker Enfants-Malades, Université Paris V, 156 rue de Vaugirard</s1><s2>75730 Paris</s2><s3>FRA</s3><sZ>2 aut.</sZ><sZ>4 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Nicole, A" sort="Nicole, A" uniqKey="Nicole A" first="A." last="Nicole">A. Nicole</name><affiliation><inist:fA14 i1="01"><s1>CNRS URA 1335, Faculté de Médecine Necker Enfants-Malades, Université Paris V, 156 rue de Vaugirard</s1><s2>75730 Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Marsac, C" sort="Marsac, C" uniqKey="Marsac C" first="C." last="Marsac">C. Marsac</name><affiliation><inist:fA14 i1="02"><s1>INSERM U75, Faculté de Médecine Necker Enfants-Malades, Université Paris V, 156 rue de Vaugirard</s1><s2>75730 Paris</s2><s3>FRA</s3><sZ>2 aut.</sZ><sZ>4 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Martinou, J C" sort="Martinou, J C" uniqKey="Martinou J" first="J. C." last="Martinou">J. C. Martinou</name><affiliation><inist:fA14 i1="03"><s1>Serono Pharmaceutical Research Institute, 14 chemin des Aulx, 1228 Plan les Ouates</s1><s2>Geneva</s2><s3>CHE</s3><sZ>5 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Sola, B" sort="Sola, B" uniqKey="Sola B" first="B." last="Sola">B. Sola</name><affiliation><inist:fA14 i1="04"><s1>Faculté de Médecine, UPRES-EA 2128, CHU Cote de Nacre</s1><s2>14033 Caen</s2><s3>FRA</s3><sZ>6 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Sinet, P M" sort="Sinet, P M" uniqKey="Sinet P" first="P.-M." last="Sinet">P.-M. Sinet</name><affiliation><inist:fA14 i1="01"><s1>CNRS URA 1335, Faculté de Médecine Necker Enfants-Malades, Université Paris V, 156 rue de Vaugirard</s1><s2>75730 Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Ceballos Picot, I" sort="Ceballos Picot, I" uniqKey="Ceballos Picot I" first="I." last="Ceballos-Picot">I. Ceballos-Picot</name><affiliation><inist:fA14 i1="01"><s1>CNRS URA 1335, Faculté de Médecine Necker Enfants-Malades, Université Paris V, 156 rue de Vaugirard</s1><s2>75730 Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">99-0512880</idno><date when="1999">1999</date><idno type="stanalyst">PASCAL 99-0512880 INIST</idno><idno type="RBID">Pascal:99-0512880</idno><idno type="wicri:Area/PascalFrancis/Corpus">001451</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Overproduction of Cu/Zn-superoxide dismutase or Bcl-2 prevents the brain mitochondrial respiratory dysfunction induced by glutathione depletion</title><author><name sortKey="Merad Saidoune, M" sort="Merad Saidoune, M" uniqKey="Merad Saidoune M" first="M." last="Merad-Saïdoune">M. Merad-Saïdoune</name><affiliation><inist:fA14 i1="01"><s1>CNRS URA 1335, Faculté de Médecine Necker Enfants-Malades, Université Paris V, 156 rue de Vaugirard</s1><s2>75730 Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Boitier, E" sort="Boitier, E" uniqKey="Boitier E" first="E." last="Boitier">E. Boitier</name><affiliation><inist:fA14 i1="02"><s1>INSERM U75, Faculté de Médecine Necker Enfants-Malades, Université Paris V, 156 rue de Vaugirard</s1><s2>75730 Paris</s2><s3>FRA</s3><sZ>2 aut.</sZ><sZ>4 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Nicole, A" sort="Nicole, A" uniqKey="Nicole A" first="A." last="Nicole">A. Nicole</name><affiliation><inist:fA14 i1="01"><s1>CNRS URA 1335, Faculté de Médecine Necker Enfants-Malades, Université Paris V, 156 rue de Vaugirard</s1><s2>75730 Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Marsac, C" sort="Marsac, C" uniqKey="Marsac C" first="C." last="Marsac">C. Marsac</name><affiliation><inist:fA14 i1="02"><s1>INSERM U75, Faculté de Médecine Necker Enfants-Malades, Université Paris V, 156 rue de Vaugirard</s1><s2>75730 Paris</s2><s3>FRA</s3><sZ>2 aut.</sZ><sZ>4 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Martinou, J C" sort="Martinou, J C" uniqKey="Martinou J" first="J. C." last="Martinou">J. C. Martinou</name><affiliation><inist:fA14 i1="03"><s1>Serono Pharmaceutical Research Institute, 14 chemin des Aulx, 1228 Plan les Ouates</s1><s2>Geneva</s2><s3>CHE</s3><sZ>5 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Sola, B" sort="Sola, B" uniqKey="Sola B" first="B." last="Sola">B. Sola</name><affiliation><inist:fA14 i1="04"><s1>Faculté de Médecine, UPRES-EA 2128, CHU Cote de Nacre</s1><s2>14033 Caen</s2><s3>FRA</s3><sZ>6 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Sinet, P M" sort="Sinet, P M" uniqKey="Sinet P" first="P.-M." last="Sinet">P.-M. Sinet</name><affiliation><inist:fA14 i1="01"><s1>CNRS URA 1335, Faculté de Médecine Necker Enfants-Malades, Université Paris V, 156 rue de Vaugirard</s1><s2>75730 Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Ceballos Picot, I" sort="Ceballos Picot, I" uniqKey="Ceballos Picot I" first="I." last="Ceballos-Picot">I. Ceballos-Picot</name><affiliation><inist:fA14 i1="01"><s1>CNRS URA 1335, Faculté de Médecine Necker Enfants-Malades, Université Paris V, 156 rue de Vaugirard</s1><s2>75730 Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14></affiliation></author></analytic><series><title level="j" type="main">Experimental neurology</title><title level="j" type="abbreviated">Exp. neurol.</title><idno type="ISSN">0014-4886</idno><imprint><date when="1999">1999</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Experimental neurology</title><title level="j" type="abbreviated">Exp. neurol.</title><idno type="ISSN">0014-4886</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animal model</term><term>Depletion</term><term>Glutathione</term><term>Mitochondria</term><term>Mouse</term><term>Oxidative stress</term><term>Parkinson disease</term><term>Pathogenesis</term><term>Respiratory chain</term><term>Superoxide dismutase</term><term>Transgenic animal</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Superoxide dismutase</term><term>Déplétion</term><term>Glutathion</term><term>Chaîne respiratoire</term><term>Mitochondrie</term><term>Stress oxydatif</term><term>Parkinson maladie</term><term>Pathogénie</term><term>Modèle animal</term><term>Animal transgénique</term><term>Souris</term></keywords></textClass></profileDesc></teiHeader><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><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0014-4886</s0></fA01><fA02 i1="01"><s0>EXNEAC</s0></fA02><fA03 i2="1"><s0>Exp. neurol.</s0></fA03><fA05><s2>158</s2></fA05><fA06><s2>2</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>Overproduction of Cu/Zn-superoxide dismutase or Bcl-2 prevents the brain mitochondrial respiratory dysfunction induced by glutathione depletion</s1></fA08><fA11 i1="01" i2="1"><s1>MERAD-SAÏDOUNE (M.)</s1></fA11><fA11 i1="02" i2="1"><s1>BOITIER (E.)</s1></fA11><fA11 i1="03" i2="1"><s1>NICOLE (A.)</s1></fA11><fA11 i1="04" i2="1"><s1>MARSAC (C.)</s1></fA11><fA11 i1="05" i2="1"><s1>MARTINOU (J. C.)</s1></fA11><fA11 i1="06" i2="1"><s1>SOLA (B.)</s1></fA11><fA11 i1="07" i2="1"><s1>SINET (P.-M.)</s1></fA11><fA11 i1="08" i2="1"><s1>CEBALLOS-PICOT (I.)</s1></fA11><fA14 i1="01"><s1>CNRS URA 1335, Faculté de Médecine Necker Enfants-Malades, Université Paris V, 156 rue de Vaugirard</s1><s2>75730 Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></fA14><fA14 i1="02"><s1>INSERM U75, Faculté de Médecine Necker Enfants-Malades, Université Paris V, 156 rue de Vaugirard</s1><s2>75730 Paris</s2><s3>FRA</s3><sZ>2 aut.</sZ><sZ>4 aut.</sZ></fA14><fA14 i1="03"><s1>Serono Pharmaceutical Research Institute, 14 chemin des Aulx, 1228 Plan les Ouates</s1><s2>Geneva</s2><s3>CHE</s3><sZ>5 aut.</sZ></fA14><fA14 i1="04"><s1>Faculté de Médecine, UPRES-EA 2128, CHU Cote de Nacre</s1><s2>14033 Caen</s2><s3>FRA</s3><sZ>6 aut.</sZ></fA14><fA20><s1>428-436</s1></fA20><fA21><s1>1999</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>9181</s2><s5>354000089404550150</s5></fA43><fA44><s0>0000</s0><s1>© 1999 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>67 ref.</s0></fA45><fA47 i1="01" i2="1"><s0>99-0512880</s0></fA47><fA60><s1>P</s1></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>Experimental neurology</s0></fA64><fA66 i1="01"><s0>USA</s0></fA66><fC01 i1="01" l="ENG"><s0>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.</s0></fC01><fC02 i1="01" i2="X"><s0>002B17G</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Superoxide dismutase</s0><s2>FE</s2><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Superoxide dismutase</s0><s2>FE</s2><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Superoxide dismutase</s0><s2>FE</s2><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Déplétion</s0><s5>04</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Depletion</s0><s5>04</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Depleción</s0><s5>04</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Glutathion</s0><s5>05</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Glutathione</s0><s5>05</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Glutatión</s0><s5>05</s5></fC03><fC03 i1="04" i2="X" l="FRE"><s0>Chaîne respiratoire</s0><s5>06</s5></fC03><fC03 i1="04" i2="X" l="ENG"><s0>Respiratory chain</s0><s5>06</s5></fC03><fC03 i1="04" i2="X" l="SPA"><s0>Cadena respiratoria</s0><s5>06</s5></fC03><fC03 i1="05" i2="X" l="FRE"><s0>Mitochondrie</s0><s5>07</s5></fC03><fC03 i1="05" i2="X" l="ENG"><s0>Mitochondria</s0><s5>07</s5></fC03><fC03 i1="05" i2="X" l="SPA"><s0>Mitocondria</s0><s5>07</s5></fC03><fC03 i1="06" i2="X" l="FRE"><s0>Stress oxydatif</s0><s5>10</s5></fC03><fC03 i1="06" i2="X" l="ENG"><s0>Oxidative stress</s0><s5>10</s5></fC03><fC03 i1="06" i2="X" l="SPA"><s0>Stress oxidativo</s0><s5>10</s5></fC03><fC03 i1="07" i2="X" l="FRE"><s0>Parkinson maladie</s0><s5>13</s5></fC03><fC03 i1="07" i2="X" l="ENG"><s0>Parkinson disease</s0><s5>13</s5></fC03><fC03 i1="07" i2="X" l="SPA"><s0>Parkinson enfermedad</s0><s5>13</s5></fC03><fC03 i1="08" i2="X" l="FRE"><s0>Pathogénie</s0><s5>17</s5></fC03><fC03 i1="08" i2="X" l="ENG"><s0>Pathogenesis</s0><s5>17</s5></fC03><fC03 i1="08" i2="X" l="SPA"><s0>Patogenia</s0><s5>17</s5></fC03><fC03 i1="09" i2="X" l="FRE"><s0>Modèle animal</s0><s5>18</s5></fC03><fC03 i1="09" i2="X" l="ENG"><s0>Animal model</s0><s5>18</s5></fC03><fC03 i1="09" i2="X" l="SPA"><s0>Modelo animal</s0><s5>18</s5></fC03><fC03 i1="10" i2="X" l="FRE"><s0>Animal transgénique</s0><s5>20</s5></fC03><fC03 i1="10" i2="X" l="ENG"><s0>Transgenic animal</s0><s5>20</s5></fC03><fC03 i1="10" i2="X" l="SPA"><s0>Animal transgénico</s0><s5>20</s5></fC03><fC03 i1="11" i2="X" l="FRE"><s0>Souris</s0><s5>21</s5></fC03><fC03 i1="11" i2="X" l="ENG"><s0>Mouse</s0><s5>21</s5></fC03><fC03 i1="11" i2="X" l="SPA"><s0>Ratón</s0><s5>21</s5></fC03><fC07 i1="01" i2="X" l="FRE"><s0>Oxidoreductases</s0><s2>FE</s2></fC07><fC07 i1="01" i2="X" l="ENG"><s0>Oxidoreductases</s0><s2>FE</s2></fC07><fC07 i1="01" i2="X" l="SPA"><s0>Oxidoreductases</s0><s2>FE</s2></fC07><fC07 i1="02" i2="X" l="FRE"><s0>Enzyme</s0></fC07><fC07 i1="02" i2="X" l="ENG"><s0>Enzyme</s0></fC07><fC07 i1="02" i2="X" l="SPA"><s0>Enzima</s0></fC07><fC07 i1="03" i2="X" l="FRE"><s0>Rodentia</s0><s2>NS</s2></fC07><fC07 i1="03" i2="X" l="ENG"><s0>Rodentia</s0><s2>NS</s2></fC07><fC07 i1="03" i2="X" l="SPA"><s0>Rodentia</s0><s2>NS</s2></fC07><fC07 i1="04" i2="X" l="FRE"><s0>Mammalia</s0><s2>NS</s2></fC07><fC07 i1="04" i2="X" l="ENG"><s0>Mammalia</s0><s2>NS</s2></fC07><fC07 i1="04" i2="X" l="SPA"><s0>Mammalia</s0><s2>NS</s2></fC07><fC07 i1="05" i2="X" l="FRE"><s0>Vertebrata</s0><s2>NS</s2></fC07><fC07 i1="05" i2="X" l="ENG"><s0>Vertebrata</s0><s2>NS</s2></fC07><fC07 i1="05" i2="X" l="SPA"><s0>Vertebrata</s0><s2>NS</s2></fC07><fC07 i1="06" i2="X" l="FRE"><s0>Système nerveux pathologie</s0><s5>69</s5></fC07><fC07 i1="06" i2="X" l="ENG"><s0>Nervous system diseases</s0><s5>69</s5></fC07><fC07 i1="06" i2="X" l="SPA"><s0>Sistema nervioso patología</s0><s5>69</s5></fC07><fC07 i1="07" i2="X" l="FRE"><s0>Système nerveux central pathologie</s0><s5>70</s5></fC07><fC07 i1="07" i2="X" l="ENG"><s0>Central nervous system disease</s0><s5>70</s5></fC07><fC07 i1="07" i2="X" l="SPA"><s0>Sistema nervosio central patología</s0><s5>70</s5></fC07><fC07 i1="08" i2="X" l="FRE"><s0>Encéphale pathologie</s0><s5>71</s5></fC07><fC07 i1="08" i2="X" l="ENG"><s0>Cerebral disorder</s0><s5>71</s5></fC07><fC07 i1="08" i2="X" l="SPA"><s0>Encéfalo patología</s0><s5>71</s5></fC07><fC07 i1="09" i2="X" l="FRE"><s0>Extrapyramidal syndrome</s0><s5>72</s5></fC07><fC07 i1="09" i2="X" l="ENG"><s0>Extrapyramidal syndrome</s0><s5>72</s5></fC07><fC07 i1="09" i2="X" l="SPA"><s0>Extrapiramidal síndrome</s0><s5>72</s5></fC07><fC07 i1="10" i2="X" l="FRE"><s0>Maladie dégénérative</s0><s5>73</s5></fC07><fC07 i1="10" i2="X" l="ENG"><s0>Degenerative disease</s0><s5>73</s5></fC07><fC07 i1="10" i2="X" l="SPA"><s0>Enfermedad degenerativa</s0><s5>73</s5></fC07><fN21><s1>333</s1></fN21></pA></standard><server><NO>PASCAL 99-0512880 INIST</NO><ET>Overproduction of Cu/Zn-superoxide dismutase or Bcl-2 prevents the brain mitochondrial respiratory dysfunction induced by glutathione depletion</ET><AU>MERAD-SAÏDOUNE (M.); BOITIER (E.); NICOLE (A.); MARSAC (C.); MARTINOU (J. C.); SOLA (B.); SINET (P.-M.); CEBALLOS-PICOT (I.)</AU><AF>CNRS URA 1335, Faculté de Médecine Necker Enfants-Malades, Université Paris V, 156 rue de Vaugirard/75730 Paris/France (1 aut., 3 aut., 7 aut., 8 aut.); INSERM U75, Faculté de Médecine Necker Enfants-Malades, Université Paris V, 156 rue de Vaugirard/75730 Paris/France (2 aut., 4 aut.); Serono Pharmaceutical Research Institute, 14 chemin des Aulx, 1228 Plan les Ouates/Geneva/Suisse (5 aut.); Faculté de Médecine, UPRES-EA 2128, CHU Cote de Nacre/14033 Caen/France (6 aut.)</AF><DT>Publication en série; Niveau analytique</DT><SO>Experimental neurology; ISSN 0014-4886; Coden EXNEAC; Etats-Unis; Da. 1999; Vol. 158; No. 2; Pp. 428-436; Bibl. 67 ref.</SO><LA>Anglais</LA><EA>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.</EA><CC>002B17G</CC><FD>Superoxide dismutase; Déplétion; Glutathion; Chaîne respiratoire; Mitochondrie; Stress oxydatif; Parkinson maladie; Pathogénie; Modèle animal; Animal transgénique; Souris</FD><FG>Oxidoreductases; Enzyme; Rodentia; Mammalia; Vertebrata; Système nerveux pathologie; Système nerveux central pathologie; Encéphale pathologie; Extrapyramidal syndrome; Maladie dégénérative</FG><ED>Superoxide dismutase; Depletion; Glutathione; Respiratory chain; Mitochondria; Oxidative stress; Parkinson disease; Pathogenesis; Animal model; Transgenic animal; Mouse</ED><EG>Oxidoreductases; Enzyme; Rodentia; Mammalia; Vertebrata; Nervous system diseases; Central nervous system disease; Cerebral disorder; Extrapyramidal syndrome; Degenerative disease</EG><SD>Superoxide dismutase; Depleción; Glutatión; Cadena respiratoria; Mitocondria; Stress oxidativo; Parkinson enfermedad; Patogenia; Modelo animal; Animal transgénico; Ratón</SD><LO>INIST-9181.354000089404550150</LO><ID>99-0512880</ID></server></inist></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/ParkinsonFranceV1/Data/PascalFrancis/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001451 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/PascalFrancis/Corpus/biblio.hfd -nk 001451 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= ParkinsonFranceV1
|flux= PascalFrancis
|étape= Corpus
|type= RBID
|clé= Pascal:99-0512880
|texte= Overproduction of Cu/Zn-superoxide dismutase or Bcl-2 prevents the brain mitochondrial respiratory dysfunction induced by glutathione depletion
}}
| This area was generated with Dilib version V0.6.29. |  |