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Methyl‐4‐phenylpyridinium ion modulates expression of mitochondrial uncoupling proteins 2, 4, and 5 in catecholaminergic (SK‐N‐SH) cells
Author(s) -
Ho Philip WingLok,
Chan David YiuLeung,
Kwok Ken HonHung,
Chu Andrew ChiYuen,
Ho Jessica WingMan,
Kung Michelle HiuWai,
Ramsden David Boyer,
Ho ShuLeong
Publication year - 2005
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.20569
Subject(s) - uncoupling protein , oxidative stress , messenger rna , reactive oxygen species , chemistry , neurotoxin , biology , microbiology and biotechnology , endocrinology , biochemistry , brown adipose tissue , gene , adipose tissue
Methyl‐4‐phenylpyridinium ion (MPP + ), a specific dopaminergic neurotoxin, inhibits mitochondrial complex I activity, generates reactive oxygen species (ROS), reduces ATP production, and induces cell death. We explored changes in expression of uncoupling proteins (UCPs 2, 4, and 5) following MPP + ‐induced toxicity in SK‐N‐SH cells over 72 hr at the transcriptional (quantification of mRNA by real‐time RT‐PCR) and translational (Western analysis) levels. UCP5 mRNA and protein were markedly up‐regulated (1 mM MPP + at 72 hr caused a twofold increase, P < 0.01), as was UCP4 mRNA, albeit to a much lesser extent. Surprisingly, UCP2 mRNA levels decreased at 24 hr ( P < 0.05) but thereafter significantly increased to greater than control levels at 72 hr ( P < 0.05), although UCP2 protein levels were decreased throughout (1 mM MPP + at 72 hr caused a reduction of 50%, P < 0.01). The increase in ROS production may be attenuated by UCP4 and UCP5 up‐regulation. The consequence of decreased UCP2 levels is unclear, although this may represent an adaptive response to declines in ATP levels, the subsequent increase in mRNA being a response to further increases in oxidative stress. © 2005 Wiley‐Liss, Inc.