Protective effect of melatonin against the 1-methyl-4-phenylpyridinium-induced inhibition of Complex I of the mitochondrial respiratory chain

被引:80
作者
Absi, E [1 ]
Ayala, A [1 ]
Machado, A [1 ]
Parrado, J [1 ]
机构
[1] Univ Sevilla, Fac Farm, Dept Bioquim Bromatol & Toxicol, E-41012 Seville, Spain
关键词
Complex I; melatonin; mitochondria; MPP+; oxidative stress; parkinson disease;
D O I
10.1034/j.1600-079X.2000.290106.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
In the present study, a novel property of melatonin is shown: a protective effect of melatonin on the respiratory chain in isolated rat liver mitochondria and in striatal synaptosomes treated with 1-methyl-4-phenylpyridinium ion (MPP+). The cellular damage caused by MPP+, a compound that produces a Parkinsonian-like syndrome in humans, is the result of the mitochondrial respiration inhibition at the Complex I level and oxidative stress induction. Treatment of mitochondria with MPP+ inhibits the respiration rate. This effect was prevented by the inclusion of melatonin in the incubation mixture. This preventive effect, which is not related to the antioxidative properties of melatonin, seems to be due to the fact that melatonin prevents MPP+ interaction with Complex I. These results suggest that melatonin may protect against the effect of several Parkinsonogenic compounds that are associated with progressive impairment of mitochondrial function and increased oxidative damage.
引用
收藏
页码:40 / 47
页数:8
相关论文
共 48 条
[1]  
ACUNACASTROVIEJ.D, 1997, LIFE SCI, V60, P23
[2]  
BATES TE, 1994, J NEUROCHEM, V63, P640
[3]   Implication of dopamine transporter system on 1-methyl-4-phenylpyridinium and rotenone effect in striatal synaptosomes [J].
Bougria, M ;
Vitorica, J ;
Cano, J ;
Machado, A .
EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION, 1995, 291 (03) :407-415
[4]   BIOENERGETIC AND OXIDATIVE STRESS IN NEURODEGENERATIVE DISEASES [J].
BOWLING, AC ;
BEAL, MF .
LIFE SCIENCES, 1995, 56 (14) :1151-1171
[5]   A PRIMATE MODEL OF PARKINSONISM - SELECTIVE DESTRUCTION OF DOPAMINERGIC-NEURONS IN THE PARS COMPACTA OF THE SUBSTANTIA NIGRA BY N-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE [J].
BURNS, RS ;
CHIUEH, CC ;
MARKEY, SP ;
EBERT, MH ;
JACOBOWITZ, DM ;
KOPIN, IJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1983, 80 (14) :4546-4550
[6]   A ONCE-REPEATED STUDY OF NOCTURNAL PLASMA MELATONIN PATTERNS AND SLEEP RECORDINGS IN 6 NORMAL YOUNG MEN [J].
CLAUSTRAT, B ;
BRUN, J ;
GARRY, P ;
ROUSSEL, B ;
SASSOLAS, G .
JOURNAL OF PINEAL RESEARCH, 1986, 3 (04) :301-310
[7]   IRREVERSIBLE INHIBITION OF MITOCHONDRIAL COMPLEX-I BY 1-METHYL-4-PHENYLPYRIDINIUM - EVIDENCE FOR FREE-RADICAL INVOLVEMENT [J].
CLEETER, MWJ ;
COOPER, JM ;
SCHAPIRA, AHV .
JOURNAL OF NEUROCHEMISTRY, 1992, 58 (02) :786-789
[8]   BETA-CARBOLINE ANALOGS OF N-METHYL-4-PHENYL-1,2,5,6-TETRA-HYDROPYRIDINE (MPTP) - ENDOGENOUS FACTORS UNDERLYING IDIOPATHIC PARKINSONISM [J].
COLLINS, MA ;
NEAFSEY, EJ .
NEUROSCIENCE LETTERS, 1985, 55 (02) :179-184
[9]  
DAVEY GP, 1992, BIOCHEM J, V288, P433
[10]   THE OXIDANT STRESS HYPOTHESIS IN PARKINSONS-DISEASE - EVIDENCE SUPPORTING IT [J].
FAHN, S ;
COHEN, G .
ANNALS OF NEUROLOGY, 1992, 32 (06) :804-812