QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (16) Citing Articles via Google Scholar Google Scholar Articles by Kenchappa, R. S. Articles by Ravindranath, V. Search for Related Content PubMed PubMed Citation Articles by Kenchappa, R. S. Articles by Ravindranath, V.

 Previous Article  |  Next Article 

The Journal of Neuroscience, October 1, 2002, 22(19):8402-8410

Thioltransferase (Glutaredoxin) Mediates Recovery of Motor Neurons from Excitotoxic Mitochondrial Injury

Rajappa S. Kenchappa^{1, 2}, Latha Diwakar¹, Michael R. Boyd³, and Vijayalakshmi Ravindranath^{1, 2}

¹ Department of Neurochemistry, National Institute of Mental Health and Neurosciences, Bangalore 560 029, India, ² National Brain Research Centre, Gurgaon 122001, India, and ³ Cancer Research Institute, College of Medicine, Mobile, Alabama 36688

Mitochondrial dysfunction involving electron transport components is implicated in the pathogenesis of several neurodegenerative disorders and is a critical event in excitotoxicity. Excitatory amino acid L--N-oxalylamino-L-alanine (L-BOAA), causes progressive corticospinal neurodegeneration in humans. In mice, L-BOAA triggers glutathione loss and protein thiol oxidation that disrupts mitochondrial complex I selectively in motor cortex and lumbosacral cord, the regions affected in humans. We examined the factors regulating postinjury recovery of complex I in CNS regions after a single dose of L-BOAA. The expression of thioltransferase (glutaredoxin), a protein disulfide oxidoreductase regulated through AP1 transcription factor was upregulated within 30 min of L-BOAA administration, providing the first evidence for functional regulation of thioltransferase during restoration of mitochondrial function. Regeneration of complex I activity in motor cortex was concurrent with increase in thioltransferase protein and activity, 1 hr after the excitotoxic insult. Pretreatment with -lipoic acid, a thiol delivery agent that protects motor neurons from L-BOAA-mediated toxicity prevented the upregulation of thioltransferase and AP1 activation, presumably by maintaining thiol homeostasis. Downregulation of thioltransferase using antisense oligonucleotides prevented the recovery of complex I in motor cortex and exacerbated the mitochondrial dysfunction in lumbosacral cord, providing support for the critical role for thioltransferase in maintenance of mitochondrial function in the CNS.

Key words: excitatory amino acid; glutaredoxin; mitochondria; motor neuron disease; glutathione; brain; complex I; oxidative stress

---

Copyright © 2002 Society for Neuroscience  0270-6474/02/22198402-09$05.00/0

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help