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Titolo:
Effect of overexpression of wild-type and mutant Cu/Zn-superoxide dismutases on oxidative stress and cell death induced by hydrogen peroxide, 4-hydroxynonenal or serum deprivation: potentiation of injury by ALS-related mutant superoxide dismutases and protection by Bcl-2
Autore:
Lee, M; Hyun, DH; Halliwell, B; Jenner, P;
Indirizzi:
Univ London Kings Coll, GKT Sch Biomed Sci, Wolfson Ctr Age Related Dis, London SE1 1UL, England Univ London Kings Coll London England SE1 1UL s, London SE1 1UL, England Natl Univ Singapore, Dept Biochem, Singapore 0511, Singapore Natl Univ Singapore Singapore Singapore 0511 , Singapore 0511, Singapore
Titolo Testata:
JOURNAL OF NEUROCHEMISTRY
fascicolo: 2, volume: 78, anno: 2001,
pagine: 209 - 220
SICI:
0022-3042(200107)78:2<209:EOOOWA>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
AMYOTROPHIC-LATERAL-SCLEROSIS; MOTOR-NEURON DISEASE; TRANSGENIC MOUSE MODEL; INCREASED 3-NITROTYROSINE; LIPID-PEROXIDATION; ALZHEIMERS-DISEASE; NITRIC-OXIDE; FAMILIAL ALS; SPINAL-CORDS; IN-VIVO;
Keywords:
ALS; apoptosis; Bcl-2; motor neurone disease; oxidative stress; superoxide dismutase;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
58
Recensione:
Indirizzi per estratti:
Indirizzo: Jenner, P Univ London Kings Coll, GKT Sch Biomed Sci, Wolfson Ctr Age Related Dis, Hodgkin Bldg,Guys Campus,London Bridge, London SE1 1UL, England Univ London Kings Coll Hodgkin Bldg,Guys Campus,London Bridge London EnglandSE1 1UL
Citazione:
M. Lee et al., "Effect of overexpression of wild-type and mutant Cu/Zn-superoxide dismutases on oxidative stress and cell death induced by hydrogen peroxide, 4-hydroxynonenal or serum deprivation: potentiation of injury by ALS-related mutant superoxide dismutases and protection by Bcl-2", J NEUROCHEM, 78(2), 2001, pp. 209-220

Abstract

Mutations in Cu/Zn-superoxide dismutase (SOD1) are associated with some cases of familial amyotrophic lateral sclerosis (ALS). We overexpressed Bcl-2, wild-type SOD1 or mutant SOD1s (G37R and G85R) in NT-2 and SK-N-MC cells. Overexpression of Bcl-2 rendered cells more resistant to apoptosis inducedby serum withdrawal, H2O2 Or 4-hydroxy-2-trans-nonenal (HNE). Overexpression of Bcl-2 had little effect on levels of protein carbonyls, lipid peroxidation, 8-hydroxyguanine (8-OHG) or 3-nitrotyrosine. Serum withdrawal or H2O2 raised levels of protein carbonyls, lipid peroxidation, 8-OHG and S-nitrotyrosine, changes that were attenuated in cells overexpressing Bcl-2. Overexpression of either SOD1 mutant tended to increase levels of lipid peroxidation, protein carbonyls, and 3-nitrotyrosine and accelerated viability lossinduced by serum withdrawal, H2O2 or HNE, accompanied by greater rises in oxidative damage parameters. The effects of mutant SOD1s were attenuated byBcl-2. By contrast, expression of wild-type SOD1 rendered cells more resistant to loss of viability induced by serum deprivation, HNE or H2O2 The levels of lipid peroxidation in wild-type SOD1 transfectants were elevated. Overexpression of mutant SOD1s makes cells more predisposed to undergo apoptosis in response to several insults. Our cellular systems appear to mimic events in patients with ALS or transgenic mice overexpressing mutant SOD1.

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Documento generato il 29/11/20 alle ore 03:34:50