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Titolo:
Oxidative damage to mitochondrial DNA and activity of mitochondrial enzymes in chronic active lesions of multiple sclerosis
Autore:
Lu, FM; Selak, M; OConnor, J; Croul, S; Lorenzana, C; Butunoi, C; Kalman, B;
Indirizzi:
Med Coll Penn & Hahnemann Univ, Dept Neurol, Philadelphia, PA 19102 USA Med Coll Penn & Hahnemann Univ Philadelphia PA USA 19102 ia, PA 19102 USA St Christophers Hosp Children, Barnett Ctr, Mitochondrial Biochem Lab, Philadelphia, PA 19133 USA St Christophers Hosp Children Philadelphia PA USA 19133 hia, PA 19133 USA Thomas Jefferson Univ, Dept Hlth Policy, Philadelphia, PA 19107 USA ThomasJefferson Univ Philadelphia PA USA 19107 hiladelphia, PA 19107 USA Rocky Mt Multiple Sclerosis Ctr, Englewood, CO USA Rocky Mt Multiple Sclerosis Ctr Englewood CO USA Ctr, Englewood, CO USA
Titolo Testata:
JOURNAL OF THE NEUROLOGICAL SCIENCES
fascicolo: 2, volume: 177, anno: 2000,
pagine: 95 - 103
SICI:
0022-510X(20000815)177:2<95:ODTMDA>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
TUMOR-NECROSIS-FACTOR; APPEARING WHITE-MATTER; CENTRAL-NERVOUS-SYSTEM; NITRIC-OXIDE SYNTHASE; COMPLEX-I DEFICIENCY; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; CYTOCHROME-OXIDASE; MONONUCLEAR-CELLS; AXONAL DAMAGE;
Keywords:
oxidative damage; neurodegeneration; multiple sclerosis;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
50
Recensione:
Indirizzi per estratti:
Indirizzo: Kalman, B Med Coll Penn & Hahnemann Univ, Dept Neurol, MS 406,245 N 15th St, Philadelphia, PA 19102 USA Med Coll Penn & Hahnemann Univ MS 406,245 N 15th St Philadelphia PA USA 19102
Citazione:
F.M. Lu et al., "Oxidative damage to mitochondrial DNA and activity of mitochondrial enzymes in chronic active lesions of multiple sclerosis", J NEUR SCI, 177(2), 2000, pp. 95-103

Abstract

Soluble products of activated immune cells include reactive oxygen species(ROS) and nitric oxide (NO) with a high potential to induce biochemical modifications and degenerative changes in areas of inflammation in the central nervous system (CNS). Previously, we demonstrated an increased productionof ROS by activated mononuclear cells (MNC) of patients with multiple sclerosis (MS) compared to those of controls, and development of oxidative damage to total DNA in association with inflammation in chronic active plaques. The current study aimed to determine whether mitochondrial (mt)DNA is affected by oxidative damage, and whether oxidative damage to mitochondrial macromolecules (including mtDNA) is associated with a decline in the activity of mitochondrial enzyme complexes. Using molecular and biochemical methods we demonstrate a trend for impaired NADH dehydrogenase (DH) activity and a possible compensatory increase in complex IV activity in association with oxidative damage to mtDNA in chronic active plaques. Immunohistochemistry confirms the increase of oxidative damage to DNA predominantly located in thecytoplasmic compartment of cells in chronic active plaques. These observations suggest that oxidative damage to macromolecules develops in association with inflammation in the CNS, and may contribute to a decline of energy metabolism in affected cells. As observed in neurodegenerative diseases of non-inflammatory origin, decreased ATP synthesis can ultimately lead to celldeath or degeneration. Therefore, elucidation of this pathway in MS deserves further studies which may identify neuroprotective strategies to preventtissue degeneration and the associated clinical disability. (C) 2000 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/04/20 alle ore 12:16:15