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已发表论文

聚 (ADP-核糖) 聚合酶 1 的甲基化和与锐钛矿型二氧化钛纳米粒子的毒性作用有关的氧化应激之间的交互作用

 

Authors Bai W, Chen Y, Gao A
Received 6 May 2015
Accepted for publication 16 July 2015
Published 1 September 2015 Volume 2015:10 Pages 5561—5569
DOI http://dx.doi.org/10.2147/IJN.S88059
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Chang Liu
Peer reviewer comments 2
Editor who approved publication:  Dr Lei Yang


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.
Keywords: titanium dioxide nanoparticles, PARP-1, oxidative stress, DNA methylation


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