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

• Published in: International journal of molecular sciences Vol. 16; no. 8; pp. 17422 - 17444
• Main Authors: Forestier, Anne, Douki, Thierry, De Rosa, Viviana, Béal, David, Rachidi, Walid
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 30.07.2015; MDPI AG
• Subjects: Alzheimer Disease - genetics; Alzheimer Disease - pathology; Alzheimer’s disease; Amyloid beta-Peptides - genetics; Amyloid beta-Peptides - secretion; Apoptosis - radiation effects; Cell Line; DDB2; DNA damage; DNA Damage - genetics; DNA Damage - radiation effects; DNA Repair; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - genetics; Gene Expression Regulation - radiation effects; Humans; Liver X Receptors; neurodegenerative disorders; nucleotide excision repair; Orphan Nuclear Receptors - biosynthesis; Orphan Nuclear Receptors - genetics; oxidative stress; Oxidative Stress - radiation effects; Physics; Ultraviolet Rays; XPC; Alzheimer’s disease; DNA damage; XPC; neurodegenerative disorders; DNA repair; nucleotide excision repair; oxidative stress; DDB2; Neurodegenerative Diseases; Brain; Oxidative Stress; Deficiency; Mammalian-Cells; Mild Cognitive Impairment; Xeroderma-Pigmentosum; Neurodegenerative disorders; DNA-Damage; Lesions; Alzheimer's disease; Apoptosis
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms160817422

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.