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Titolo:
Selective dopaminergic vulnerability: 3,4-dihydroxyphenylacetaldehyde targets mitochondria
Autore:
Kristal, BS; Conway, AD; Brown, AM; Jain, JC; Ulluci, PA; Li, SW; Burke, WJ;
Indirizzi:
Cornell Univ, Coll Med, Burke Med Res Inst, Dementia Res Serv, White Plains, NY 10605 USA Cornell Univ White Plains NY USA 10605 s Serv, White Plains, NY 10605 USA Cornell Univ, Weill Med Coll, Dept Biochem, New York, NY 10021 USA CornellUniv New York NY USA 10021 , Dept Biochem, New York, NY 10021 USA Cornell Univ, Weill Med Coll, Dept Neurosci, New York, NY 10021 USA Cornell Univ New York NY USA 10021 Dept Neurosci, New York, NY 10021 USA St Louis VA Med Ctr, Dept Neurol, St Louis, MO USA St Louis VA Med Ctr StLouis MO USA d Ctr, Dept Neurol, St Louis, MO USA St Louis Univ, St Louis, MO 63103 USA St Louis Univ St Louis MO USA 63103St Louis Univ, St Louis, MO 63103 USA Univ Notre Dame, Ctr Environm Sci & Technol, Dept Civil Engn & Geol Sci, ICPMS Lab, Notre Dame, IN 46556 USA Univ Notre Dame Notre Dame IN USA 46556PMS Lab, Notre Dame, IN 46556 USA ESA Inc, Chelmsford, MA USA ESA Inc Chelmsford MA USAESA Inc, Chelmsford, MA USA St Louis VA Med Ctr, Dept Chem, St Louis, MO USA St Louis VA Med Ctr St Louis MO USA Med Ctr, Dept Chem, St Louis, MO USA
Titolo Testata:
FREE RADICAL BIOLOGY AND MEDICINE
fascicolo: 8, volume: 30, anno: 2001,
pagine: 924 - 931
SICI:
0891-5849(20010415)30:8<924:SDV3T>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
NOREPINEPHRINE TRANSMITTER METABOLITE; PERMEABILITY TRANSITION PORE; RAT PHEOCHROMOCYTOMA CELLS; COMPLEX-I DEFICIENCY; PARKINSONS-DISEASE; CYCLOSPORINE-A; DIETARY RESTRICTION; MONOAMINE-OXIDASE; PC12 CELLS; T-BUTYLHYDROPEROXIDE;
Keywords:
free radicals; Parkinson's disease; reactive species; dopamine; mitochondria; permeability transition;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
65
Recensione:
Indirizzi per estratti:
Indirizzo: Kristal, BS Cornell Univ, Coll Med, Burke Med Res Inst, Dementia Res Serv,785 Mamaroneck Ave, White Plains, NY 10605 USA Cornell Univ 785 MamaroneckAve White Plains NY USA 10605 USA
Citazione:
B.S. Kristal et al., "Selective dopaminergic vulnerability: 3,4-dihydroxyphenylacetaldehyde targets mitochondria", FREE RAD B, 30(8), 2001, pp. 924-931

Abstract

Parkinson's disease (PD) is a major cause of age-related morbidity and mortality, present in nearly 1% of individuals at ages 70-79 and similar to2.5% of individuals at age 85. L-DOPA (L-dihydroxyphenylalanine), which is metabolized to dopamine by dopa decarboxylase. is the primary therapy for PD, but may also contribute to disease progression. Association between mitochondrial dysfunction, monoamine oxidase (MAO) activity, and dopaminergic neurotoxicity has been repeatedly observed, but the mechanisms underlying selective dopaminergic neuron depletion in aging and neurodegenerative disordersremain unclear. We now report that 3,4-dihydroxyphenylacetaldehyde (DOPAL), the MAO metabolite of dopamine, is more cytotoxic in neuronally differentiated PC 12 cells than dopamine and several of its metabolites. In isolated, energetically compromised mitochondria, physiological concentrations of DOPAL induced the permeability transition (PT), a trigger for cell death. Dopamine was > 1000-fold less potent. PT inhibitors protected both mitochondria and cells against DOPAL. Sensitivity to DOPAL was reduced greater than or equal to 30-fold in fully energized mitochondria, suggesting that mitochondrial respiration may increase resistance to PT induction by the endogenous DOPAL in the substantia nigra. These data provide a potential mechanism of action for L-DOPA-mediated neurotoxicity and suggest two potentially interactive mechanisms for the selective vulnerability of neurons exposed to dopamine. (C) 2001 Elsevier Science Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 31/03/20 alle ore 10:11:03