Abstract
Multiple sclerosis (MS) is an inflammatory neurodegenerative disease. Recently, decreased
expression of nuclear encoded electron transport chain genes was found in neurons
in MS cortex. To understand the transcriptional mechanisms responsible for the coordinate
down regulation of these genes, we performed electrophoretic mobility shifts with
nuclear extracts isolated from gray matter from nonlesion areas of postmortem MS and
control cortex. Nine tissue blocks from eight different MS brains and six matched
control blocks from five control brains were analyzed. We identified a decrease in
a transcription factor complex containing nuclear respiratory factor 2 (NRF-2) in
nuclear extracts isolated from MS cortex. This decrease is correlated with decreased
expression of electron transport chain subunit genes and increased oxidative damage
measured by increased anti-nitrotyrosine immunoreactivity. We conclude that in MS
cortex a chronic increase in oxidative stress leads to aberrant regulation of transcription
of genes involved in energy metabolism.
Keywords
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Article info
Publication history
Published online: February 02, 2009
Accepted:
January 8,
2009
Received in revised form:
December 9,
2008
Received:
January 11,
2008
Identification
Copyright
© 2009 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
