Increased oxidative damage and mitochondrial abnormalities in the peripheral blood of Huntington's disease patients.
Increased oxidative stress and mitochondrial abnormalities contribute to neuronal dysfunction in Huntington's disease (HD). We investigated whether these pathological changes in HD brains may also be present in peripheral tissues. Leukocyte 8-hydroxydeoxyguanosine (8-OHdG) and plasma malondialdehyde (MDA) were elevated, and activities of erythrocyte Cu/Zn-superoxide dismutase (Cu/Zn-SOD) and glutathione peroxidase (GPx) reduced in 16 HD patients when compared to 36 age- and gender-matched controls. Deleted and total mitochondrial DNA (mtDNA) copy numbers were increased, whereas the mRNA expression levels of mtDNA-encoded mitochondrial enzymes are not elevated in HD leukocytes compared to the normal controls. Plasma MDA levels also significantly correlated with HD disease severity. These results indicate means to suppress oxidative damage or to restore mitochondrial functions may be beneficial to HD patients. Plasma MDA may be used as a potential biomarker to test treatment efficacy in the future, if confirmed in a larger, longitudinal study.
Chen
Chiung-Mei
CM
Department of Neurology, Chang Gung Memorial Hospital, Chang-Gung University College of Medicine, Taipei, Taiwan. cmchen@adm.cgmh.org.tw
Wu
Yih-Ru
YR
Cheng
Mei-Ling
ML
Liu
Jun-Liang
JL
Lee
Yu-May
YM
Lee
Po-Wei
PW
Soong
Bing-Wen
BW
Chiu
Daniel Tsun-Yee
DT
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000494:pharmacology; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000097:blood*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress; D013482:Superoxide Dismutase / Q000097:blood
D015415:Biomarkers; D004272:DNA, Mitochondrial; D008315:Malondialdehyde; D000080242:8-Hydroxy-2'-Deoxyguanosine; D013482:Superoxide Dismutase; D003849:Deoxyguanosine