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Titolo:
(E)-4-HYDROXY-2-NONENAL MAY BE INVOLVED IN THE PATHOGENESIS OF PARKINSONS-DISEASE
Autore:
SELLEY ML;
Indirizzi:
PAN AUSTRALIA LABS PTY LTD,POB 3641 WESTON ACT 2611 AUSTRALIA PAN AUSTRALIA LABS PTY LTD FYSHWICK ACT AUSTRALIA AUSTRALIAN NATL UNIV,JOHN CURTIN SCH MED RES,DIV CLIN SCI,CANBERRA HOSP GARRAN ACT AUSTRALIA
Titolo Testata:
Free radical biology & medicine
fascicolo: 2, volume: 25, anno: 1998,
pagine: 169 - 174
SICI:
0891-5849(1998)25:2<169:(MBIIT>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
SUBSTANTIA-NIGRA; LIPID-PEROXIDATION; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE MPTP; DOPAMINERGIC-NEURONS; GLUTATHIONE; N-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; METABOLISM; IRON; TOXICITY; PRODUCT;
Keywords:
PARKINSONS DISEASE; N-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; LIPID PEROXIDATION; (E)-4-HYDROXY-2-NONENAL; GLUTATHIONE; FREE RADICAL;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
44
Recensione:
Indirizzi per estratti:
Citazione:
M.L. Selley, "(E)-4-HYDROXY-2-NONENAL MAY BE INVOLVED IN THE PATHOGENESIS OF PARKINSONS-DISEASE", Free radical biology & medicine, 25(2), 1998, pp. 169-174

Abstract

(E)-4-Hydroxy-2-nonenal (HNE) is a toxic end-product of the free radical-stimulated peroxidation of phospholoipid-bound arachidonic acid incell membranes. There is a growing body of evidence to suggest that free radicals may play an important role in the pathology of Parkinson's disease. HNE is highly electrophilic and is conjugated to reduced glutathione (GSH) by glutathione S-transferase. The depletion of GSH in the substantia nigra of Parkinson's patients and in the brainstem of mice treated with the neurotoxin N-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) prompted this study on the concentrations of HNE in the cerebrospinal fluid (CSF) and plasma of Parkinson's patients and the brainstem of mice treated with MPTP. HNE was identified and quantitatedby a highly specific and sensitive method based on the gas chromatography-negative-ion chemical ionisation mass spectrometry of the O-pentafluorobenzyl oxime derivative using 9D(3)-4-hydroxy-2-nonenal as an internal standard. The mean concentration of HNE in the CSF of patients with Parkinson's disease was 1.47 +/- 0.76 mu M (mean +/- SD, n = IO),while the concentration in the CSF of a group of control patients was0.38 +/- 0.14 mu M (n = 10; p <.01). The mean concentration of HNE inthe plasma of Parkinson's patients was 0.68 +/- 0.15 mu M (n = 20) and the concentration in the control group was 0.47 +/-: 0 12 mu M (n = 20; p <.05). The mean peak concentration of HNE in the brainstem of mice after a single s.c, dose of MPTP (40 mg/kg) was 3.62 +/- 0.36 nM/g wet wt. (n = 17) at 12 h while the control value was 0.45 +/- 0.05 nM/g wet wt. (n = 20; p <.05). The GSH concentration in the brainstem of MPTP-treated mice at 24 h. was 0.65 +/- 0.03 mu M/g wet wt. (n = 14) and the control value was 1.25 +/- 0.03 mu M/g wet wt. (n = 20; p <.01). The corresponding concentration of GSH-HNE-conjugate at 24 h was 0.32 +/- 0.09 mu M/g wet wt. (n = 12) compared with a control value of 0.05 +/- 0.02 (n = 16; p <.01). After treatment with cu-tocopherol (2.35g/kg s.c. daily X 3) the mean concentration of HNE 12 hr. after MPTP injection was 0.89 +/- 0.06 nM/g wet wt. (n = 18). The HNE concentration in a group not treated with cr-tocopherol prior to MPTP injection was 3.49 +/- 0.09 nM/g wet wt. (n = 14; p <.05). The concentration of GSH in the mice pretreated with ar-tocopherol before MPTP injection was1.14 +/- 0.02 mu M/g wet wt. (n = 17) at 24 h compared to 0.61 +/-:0.02 mu M/g wet wt. (n = 14) in the untreated mice (p <.05). The direct injection of HME (I, 10, 100, 1,000 mu M) into the substantia nigra caused a dose dependent depletion of GSH in the brainstem of mice. The mean concentration of GSH 24 hr after the injection of 100 mu M of HNE was 0.43 +/- 0.22 mu M/g wet wt. (n = 4) compared with a control valueof 1.48 +/- 0.02 mu M/g wet wt. (n = 8; p <.05). The corresponding concentration of GSH-HNE-conjugate was 0.32 +/- 0.12 mu M/g wet wt. (n =4) while the control value was 0.04 +/- 0.02 mu M/g wet wt. (n = 8). These data suggest that HNE may be a causeative neurotoxin in Parkinson's disease and that HNE may also be involved in MPTP toxicity. (C) 1998 Elsevier Science Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 11/07/20 alle ore 21:02:55