Oxidative damage to mitochondrial DNA in Huntington's disease parietal cortex

被引:167
作者
Polidori, MC
Mecocci, P
Browne, SE
Senin, U
Beal, MF
机构
[1] Perugia Univ Hosp, Inst Gerontol & Geriatr, Perugia, Italy
[2] Massachusetts Gen Hosp, Neurol Serv, Neurochem Lab, Boston, MA 02114 USA
[3] Harvard Univ, Sch Med, Boston, MA USA
关键词
Huntington's disease; mitochondria; DNA; oxidative stress; Free radicals; 8-Hydroxy-2-deoxyguanosine;
D O I
10.1016/S0304-3940(99)00578-9
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Oxidative damage to DNA may play a role in both normal aging and in neurodegenerative diseases. Using a sensitive high-performance liquid chromatography (HPLC) assay, we examined concentrations of 8-hydroxy-2-deoxyguanosine (OH(8)dG) in mitochondrial DNA (mtDNA) isolated from frontal and parietal cerebral cortex and from cerebellum in 22 Huntington's disease (HD) patients and 15 age-matched normal controls. A significant increase in OH(8)dG in mtDNA of parietal cortex was found in HD patients as compared with controls, while there were no significant changes in frontal cortex or cerebellum. The present findings are consistent with regionally specific oxidative damage in HD, which may be a further evidence of a metabolic defect. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:53 / 56
页数:4
相关论文
共 21 条
[1]   AGING, ENERGY, AND OXIDATIVE STRESS IN NEURODEGENERATIVE DISEASES [J].
BEAL, MF .
ANNALS OF NEUROLOGY, 1995, 38 (03) :357-366
[2]   CHRONIC MITOCHONDRIAL ENERGY IMPAIRMENT PRODUCES SELECTIVE STRIATAL DEGENERATION AND ABNORMAL CHOREIFORM MOVEMENTS IN PRIMATES [J].
BROUILLET, E ;
HANTRAYE, P ;
FERRANTE, RJ ;
DOLAN, R ;
LEROYWILLIG, A ;
KOWALL, NW ;
BEAL, MF .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (15) :7105-7109
[3]   Oxidative damage and metabolic dysfunction in Huntington's disease: Selective vulnerability of the basal ganglia [J].
Browne, SE ;
Bowling, AC ;
MacGarvey, U ;
Baik, MJ ;
Berger, SC ;
Muqit, MMK ;
Bird, ED ;
Beal, MF .
ANNALS OF NEUROLOGY, 1997, 41 (05) :646-653
[4]   DISTRIBUTION OF PHOSPHATE-ACTIVATED GLUTAMINASE, SUCCINIC-DEHYDROGENASE, PYRUVATE-DEHYDROGENASE AND GAMMA-GLUTAMYL-TRANSFERASE TRANSPEPTIDASE IN POST-MORTEM BRAIN FROM HUNTINGTONS-DISEASE AND AGONAL CASES [J].
BUTTERWORTH, J ;
YATES, CM ;
REYNOLDS, GP .
JOURNAL OF THE NEUROLOGICAL SCIENCES, 1985, 67 (02) :161-171
[5]   CHEMICAL DETERMINATION OF FREE RADICAL-INDUCED DAMAGE TO DNA [J].
DIZDAROGLU, M .
FREE RADICAL BIOLOGY AND MEDICINE, 1991, 10 (3-4) :225-242
[6]   IN-SITU EVIDENCE FOR DNA FRAGMENTATION IN HUNTINGTONS-DISEASE STRIATUM AND ALZHEIMERS-DISEASE TEMPORAL LOBES [J].
DRAGUNOW, M ;
FAULL, RLM ;
LAWLOR, P ;
BEILHARZ, EJ ;
SINGLETON, K ;
WALKER, EB ;
MEE, E .
NEUROREPORT, 1995, 6 (07) :1053-1057
[7]  
Ferrante R. J., 1996, Society for Neuroscience Abstracts, V22, P227
[8]   OXIDATIVE DAMAGE TO DNA DURING AGING - 8-HYDROXY-2'-DEOXYGUANOSINE IN RAT ORGAN DNA AND URINE [J].
FRAGA, CG ;
SHIGENAGA, MK ;
PARK, JW ;
DEGAN, P ;
AMES, BN .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (12) :4533-4537
[9]  
IRAZU C E, 1990, Journal of Experimental Pathology (New York), V5, P1
[10]  
JENKINS BG, 1993, NEUROLOGY, V43, P2685