title: Cross talk between poly(ADP-ribose) polymerase 1 methylation and oxidative stress involved in the toxic effect of anatase titanium dioxide nanoparticles.
abstract: Given the tremendous growth in the application of titanium dioxide nanoparticles (TNPs), concerns about the potential health hazards of TNPs to humans have been raised. Poly(ADP-ribose) polymerase 1 (PARP-1), a highly conserved DNA-binding protein, is involved in many molecular and cellular processes. Limited data demonstrated that certain nanomaterials induced the aberrant hypermethylation of PARP-1. However, the mechanism involved in TNP-induced PARP-1 abnormal methylation has not been studied. A549 cells were incubated with anatase TNPs (22.1 nm) for 24 hours pretreatment with or without methyltransferase inhibitor 5-aza-2'-deoxycytidine and the reactive oxygen species (ROS) scavenger α-lipoic acid to assess the possible role of methylation and ROS in the toxic effect of TNPs. After TNPs characterization, a battery of assays was performed to evaluate the toxic effect of TNPs, PARP-1 methylation status, and oxidative damage. Results showed that TNPs decreased the cell viability in a dose-dependent manner, in accordance with the increase of lactate dehydrogenase activity, which indicated membrane damage of cells. Similar to the high level of PARP-1 methylation, the generation of ROS was significantly increased after exposure to TNPs for 24 hours. Furthermore, α-lipoic acid decreased TNP-induced ROS generation and then attenuated TNP-triggered PARP-1 hypermethylation. Meanwhile, 5-aza-2'-deoxycytidine simultaneously decreased the ROS generation induced by TNPs, resulting in the decline of PARP-1 methylation. In summary, TNPs triggered the aberrant hypermethylation of the PARP-1 promoter and there was a cross talk between oxidative stress and PARP-1 methylation in the toxic effect of TNPs.
authors.affiliation: Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing, People's Republic of China ; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Wenlin
authors.initials: W
authors.lastname: Bai
authors.affiliation: Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing, People's Republic of China ; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Yujiao
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing, People's Republic of China ; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Ai
authors.initials: A
authors.lastname: Gao
mesh_terms: D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000077209:Decitabine; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008745:Methylation; D008780:Methyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D018384:Oxidative Stress / Q000187:drug effects*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D017382:Reactive Oxygen Species / Q000378:metabolism; D008063:Thioctic Acid / Q000737:chemistry / Q000494:pharmacology; D014025:Titanium / Q000633:toxicity*
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; C009495:titanium dioxide; D008063:Thioctic Acid; D000077209:Decitabine; D014025:Titanium; D007770:L-Lactate Dehydrogenase; D008780:Methyltransferases; D011065:Poly(ADP-ribose) Polymerases; D001374:Azacitidine
keywords: DNA methylation; PARP-1; oxidative stress; titanium dioxide nanoparticles