TY - JOUR
T1 - Knockdown of uncoupling protein-5 in neuronal SH-SY5Y cells
T2 - Effects on MPP+-induced mitochondrial membrane depolarization, ATP deficiency, and oxidative cytotoxicity
AU - Ho, Philip Wing Lok
AU - Chu, Andrew Chi Yuen
AU - Kwok, Ken Hon Hung
AU - Kung, Michelle Hiu Wai
AU - Ramsden, David Boyer
AU - Ho, Shu Leong
PY - 2006/11/1
Y1 - 2006/11/1
N2 - Uncoupling proteins (UCPs) uncouple oxidative phosphorylation from ATP synthesis by dissipating proton gradient across mitochondrial inner membrane. The physiological role of neuronal specific UCP5 is unknown. We explored the effects of reduced UCP5 expression on mitochondrial membrane potential (MMP), oxidative stress, ATP levels, and cell viability, under normal and MPP +-induced cytotoxic conditions, in human catecholaminergic SH-SY5Y cells. UCP5 expression was reduced by 56% by siRNA, compared to scrambled-siRNA controls. UCP5 knockdown induced apoptosis but did not affect basal levels of ATP, oxidative stress and MMP in the cells under normal conditions. However, UCP5 knockdown increased MPP+-induced cytotoxicity by 15% and oxidative stress levels by 40%, and partially restored MPP+-induced mitochondrial depolarization by 57%. UCP2 and UCP4 expression were unaffected by UCP5 knockdown. Exacerbation of cytotoxicity, oxidative stress and modification of MMP with reduced UCP5 expression in the face of MPP+ toxicity suggest that UCP5 might be physiologically important in the pathology of oxidative stress-induced neurodegeneration.
AB - Uncoupling proteins (UCPs) uncouple oxidative phosphorylation from ATP synthesis by dissipating proton gradient across mitochondrial inner membrane. The physiological role of neuronal specific UCP5 is unknown. We explored the effects of reduced UCP5 expression on mitochondrial membrane potential (MMP), oxidative stress, ATP levels, and cell viability, under normal and MPP +-induced cytotoxic conditions, in human catecholaminergic SH-SY5Y cells. UCP5 expression was reduced by 56% by siRNA, compared to scrambled-siRNA controls. UCP5 knockdown induced apoptosis but did not affect basal levels of ATP, oxidative stress and MMP in the cells under normal conditions. However, UCP5 knockdown increased MPP+-induced cytotoxicity by 15% and oxidative stress levels by 40%, and partially restored MPP+-induced mitochondrial depolarization by 57%. UCP2 and UCP4 expression were unaffected by UCP5 knockdown. Exacerbation of cytotoxicity, oxidative stress and modification of MMP with reduced UCP5 expression in the face of MPP+ toxicity suggest that UCP5 might be physiologically important in the pathology of oxidative stress-induced neurodegeneration.
KW - ATP
KW - Mitochondrial dysfunction
KW - MPP
KW - Oxidative stress
KW - Parkinson's disease
KW - Uncoupling protein
UR - http://www.scopus.com/inward/record.url?scp=33750490401&partnerID=8YFLogxK
U2 - 10.1002/jnr.21034
DO - 10.1002/jnr.21034
M3 - Journal article
C2 - 16941493
AN - SCOPUS:33750490401
SN - 0360-4012
VL - 84
SP - 1358
EP - 1366
JO - Journal of Neuroscience Research
JF - Journal of Neuroscience Research
IS - 6
ER -