Hermon M, Cairns N, Egly J M, Fery A, Labudova O, Lubec G
University of Vienna, Department of Pediatrics, Austria.
Neurosci Lett. 1998 Jul 17;251(1):45-8. doi: 10.1016/s0304-3940(98)00488-1.
Although deficient DNA repair was proposed for neurodegenerative disorders including Down syndrome (DS), repair proteins for nucleotide excision repair have not been studied in brain yet. As one of the hypotheses for the pathogenesis of brain damage in DS and Alzheimer's disease (AD), is oxidative stress, and cells of patients with DS were shown to be more susceptible to ionizing irradiation. We decided to study expression of excision repair-cross-complementing (ERCC) gene products, proteins 80 and 89, representatives of repair genes known to be involved in the repair of different types of DNA damage. ERCC2-protein 80 kDa and ERCC3-protein p89 were determined in five individual brain regions of controls, aged DS and AD patients. Although different in the individual regions, DNA repair proteins were consistently higher in temporal and frontal lobes of patients with DS and higher in all brain regions of patients with AD. Our results are the first to describe DNA repair gene protein patterns in human brain regions providing the basis for further studies in this area. We showed that DNA repair genes ERCC2 and ERCC3 (excision-repair-cross-complementing) for nucleotide excision repair were increased at the protein level with the possible biological meaning that this increase may be compatible with and indicate ongoing (oxidative?) DNA damage.
尽管有人提出DNA修复缺陷与包括唐氏综合征（DS）在内的神经退行性疾病有关，但核苷酸切除修复的修复蛋白在大脑中的研究尚未开展。作为DS和阿尔茨海默病（AD）脑损伤发病机制的假说之一是氧化应激，并且已表明DS患者的细胞对电离辐射更敏感。我们决定研究切除修复交叉互补（ERCC）基因产物、80 kDa蛋白和89 kDa蛋白的表达，这些是已知参与不同类型DNA损伤修复的修复基因的代表。在对照、老年DS患者和AD患者的五个不同脑区中测定了ERCC2蛋白（80 kDa）和ERCC3蛋白（p89）。尽管在各个脑区有所不同，但DS患者颞叶和额叶中的DNA修复蛋白始终较高，而AD患者所有脑区中的DNA修复蛋白均较高。我们的结果首次描述了人类脑区中的DNA修复基因蛋白模式，为该领域的进一步研究提供了基础。我们表明，用于核苷酸切除修复的DNA修复基因ERCC2和ERCC3（切除修复交叉互补）在蛋白质水平上有所增加，其可能的生物学意义在于这种增加可能与正在进行的（氧化？）DNA损伤相符并表明这种损伤的存在。
