Combination of Aβ Secretion and Oxidative Stress in an Alzheimer-Like Cell Line Leads to the Over-Expression of the Nucleotide Excision Repair Proteins DDB2 and XPC

International Journal of Molecular Sciences

Anne Forestier²  Thierry Douki²  Viviana De Rosa²  David Bບl²  Walid Rachidi¹ 

[1] Laboratoire Lésions des Acides Nucléiques, Université Joseph Fourier-Grenoble 1/CEA/Institut Nanoscience et Cryogénie/SCIB, UMR-E3, Grenoble, France;

关键词: neurodegenerative disorders;    Alzheimer’s disease;    DNA damage;    DNA repair;    nucleotide excision repair;    XPC;    DDB2;    oxidative stress;   

DOI  :  10.3390/ijms160817422

来源: mdpi

【 摘 要 】

Repair of oxidative DNA damage, particularly Base Excision Repair (BER), impairment is often associated with Alzheimer’s disease pathology. Here, we aimed at investigating the complete Nucleotide Excision Repair (NER), a DNA repair pathway involved in the removal of bulky DNA adducts, status in an Alzheimer-like cell line. The level of DNA damage was quantified using mass spectrometry, NER gene expression was assessed by qPCR, and the NER protein activity was analysed through a modified version of the COMET assay. Interestingly, we found that in the presence of the Amyloid β peptide (Aβ), NER factors were upregulated at the mRNA level and that NER capacities were also specifically increased following oxidative stress. Surprisingly, NER capacities were not differentially improved following a typical NER-triggering of ultraviolet C (UVC) stress. Oxidative stress generates a differential and specific DNA damage response in the presence of Aβ. We hypothesized that the release of NER components such as DNA damage binding protein 2 (DDB2) and Xeroderma Pigmentosum complementation group C protein (XPC) following oxidative stress might putatively involve their apoptotic role rather than DNA repair function.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.