Mitochondrial complex I inhibition in cerebral cortex of immature rats following homocysteic acid-induced seizures

被引:43
作者
Folbergrova, Jaroslava
Jesina, Pavel
Drahota, Zdenek
Lisy, Vaclav
Haugvicova, Renata
Vojtiskova, Alena
Houstek, Josef
机构
[1] Acad Sci Czech Republ, Inst Physiol, CR-14220 Prague 4, Czech Republic
[2] Acad Sci Czech Republ, Inst Microbiol, CR-14220 Prague 4, Czech Republic
关键词
immature rats; DL-homocysteic acid-induced seizures; mitochondrial respiratory chain; complex I inhibition; respiration; energy metabolites; free radicals; protection;
D O I
10.1016/j.expneurol.2006.12.010
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The major finding of the present study concerns the marked decrease of respiratory chain complex I activity in the cerebral cortex of immature rats following seizures induced by bilateral intracerebroventricular infusion of DL-homocysteic acid (600 nmol/side). This decrease was already evident during the acute phase of seizures (60-90 min after infusion) and persisted for at least 20 h after the seizures. It was selective for complex I since activities of complex II and IV and citrate synthase remained unaffected. Inhabition of complex I activity was not associated with changes in complex I content. Based on enhanced lipoperoxidation and decreased aconitase activity, it can be postulated that oxidative modification is most likely responsible for the observed inhibition. Mitochondrial respiration, as well as cortical ATP levels remained in the control range, apparently due to excess capacity of the complex I documented by energy thresholds. On the other hand, the enhanced production of reactive oxygen species by inhibited complex I was observedin mitochondria from HCA-treated animals. The decrease of complex I activity was substantially attenuated when animals were treated with substances providing an anticonvulsant effect and also with selected free radical scavengers. We can assume that inhibition of complex I may elicit enhanced formation of reactive oxygen species and contribute thus to neuronal injury demonstrated in this model. (c) 2007 Elsevier Inc. All rights reserved.
引用
收藏
页码:597 / 609
页数:13
相关论文
共 73 条
[11]   Pharmacology and functions of metabotropic glutamate receptors [J].
Conn, PJ ;
Pin, JP .
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, 1997, 37 :205-237
[12]   Energy thresholds in brain mitochondria - Potential involvement in neurodegeneration [J].
Davey, GP ;
Peuchen, S ;
Clark, JB .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (21) :12753-12757
[13]  
Davey GP, 1996, J NEUROCHEM, V66, P1617
[14]  
DELACRUZ VP, 2005, NEUROSCIENCE, V135, P463
[15]   Mitochondrial encephalomyopathies: an update [J].
DiMauro, S ;
Hirano, M .
NEUROMUSCULAR DISORDERS, 2005, 15 (04) :276-286
[16]   Mitochondria and calcium: from cell signalling to cell death [J].
Duchen, MR .
JOURNAL OF PHYSIOLOGY-LONDON, 2000, 529 (01) :57-68
[17]  
DUGAN LL, 1995, J NEUROSCI, V15, P6377
[18]   Energy metabolism in mammalian brian during development [J].
Erecinska, M ;
Cherian, S ;
Silver, IA .
PROGRESS IN NEUROBIOLOGY, 2004, 73 (06) :397-445
[19]  
FOLBERGROVA J, 1972, J NEUROCHEM, V19, P2497
[20]  
Folbergrová J, 2004, EPILEPSIA, V45, P109