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.
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.
Laboratoire Lésions des Acides Nucléiques, Université Joseph Fourier-Grenoble 1/CEA/Institut Nanoscience et Cryogénie/SCIB, UMR-E3, Grenoble, France. ann.forestier@gmail.com.
Anne
A
Forestier
Laboratoire Lésions des Acides Nucléiques, Université Joseph Fourier-Grenoble 1/CEA/Institut Nanoscience et Cryogénie/SCIB, UMR-E3, Grenoble, France. thierry.douki@cea.fr.
Thierry
T
Douki
Laboratoire Lésions des Acides Nucléiques, Université Joseph Fourier-Grenoble 1/CEA/Institut Nanoscience et Cryogénie/SCIB, UMR-E3, Grenoble, France. viviana.derosa@ibb.cnr.it.
Viviana
V
De Rosa
Laboratoire Lésions des Acides Nucléiques, Université Joseph Fourier-Grenoble 1/CEA/Institut Nanoscience et Cryogénie/SCIB, UMR-E3, Grenoble, France. david.beal@cea.fr.
David
D
Béal
Laboratoire Lésions des Acides Nucléiques, Université Joseph Fourier-Grenoble 1/CEA/Institut Nanoscience et Cryogénie/SCIB, UMR-E3, Grenoble, France. walid.rachidi@cea.fr.
Walid
W
Rachidi
D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000528:radiation effects; D002460:Cell Line; D004249:DNA Damage / Q000235:genetics / Q000528:radiation effects; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000528:radiation effects; D006801:Humans; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors / Q000096:biosynthesis* / Q000235:genetics; D018384:Oxidative Stress / Q000528:radiation effects; D014466:Ultraviolet Rays
D016229:Amyloid beta-Peptides; C117669:DDB2 protein, human; D004268:DNA-Binding Proteins; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; C086984:XPC protein, human
Alzheimer’s disease; DDB2; DNA damage; DNA repair; XPC; neurodegenerative disorders; nucleotide excision repair; oxidative stress