TY - JOUR
T1 - Methyl-4-phenylpyridinium ion modulates expression of mitochondrial uncoupling proteins 2, 4, and 5 in catecholaminergic (SK-N-SH) cells
AU - Ho, Philip Wing Lok
AU - Chan, David Yiu Leung
AU - Kwok, Ken Hon Hung
AU - Chu, Andrew Chi Yuen
AU - Ho, Jessica Wing Man
AU - Kung, Michelle Hiu Wai
AU - Ramsden, David Boyer
AU - Ho, Shu Leong
PY - 2005/7/15
Y1 - 2005/7/15
N2 - 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.
AB - 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.
KW - Mitochondria
KW - MPP
KW - Neuroprotection
KW - Oxidative stress
KW - Uncoupling protein
UR - http://www.scopus.com/inward/record.url?scp=23844467747&partnerID=8YFLogxK
U2 - 10.1002/jnr.20569
DO - 10.1002/jnr.20569
M3 - Journal article
C2 - 15948157
AN - SCOPUS:23844467747
SN - 0360-4012
VL - 81
SP - 261
EP - 268
JO - Journal of Neuroscience Research
JF - Journal of Neuroscience Research
IS - 2
ER -