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Cross talk between poly(ADP-ribose) polymerase 1 methylation and oxidative stress involved in the toxic effect of anatase titanium dioxide nanoparticles.

Bai W, Chen Y, Gao A - Int J Nanomedicine (2015)

Bottom Line: Limited data demonstrated that certain nanomaterials induced the aberrant hypermethylation of PARP-1.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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus

Effects of inhibitors, 5-aza or α-LA, on TNP-induced ROS generation in A549 cells.Notes: The methyltransferase inhibitor, 5-aza decreased TNPs-induced ROS generation (A); the antioxidant agent, α-LA suppressed ROS generation triggered by TNPs (B). Data are expressed as mean ± SD; n=5, *P<0.05, compared with control; #P<0.05, compared with TNPs.Abbreviations: 5-aza, 5-aza-2′-deoxycytidine; α-LA, α-lipoic acid; TNPs, titanium dioxide nanoparticles; ROS, reactive oxygen species; SD, standard deviation.
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f5-ijn-10-5561: Effects of inhibitors, 5-aza or α-LA, on TNP-induced ROS generation in A549 cells.Notes: The methyltransferase inhibitor, 5-aza decreased TNPs-induced ROS generation (A); the antioxidant agent, α-LA suppressed ROS generation triggered by TNPs (B). Data are expressed as mean ± SD; n=5, *P<0.05, compared with control; #P<0.05, compared with TNPs.Abbreviations: 5-aza, 5-aza-2′-deoxycytidine; α-LA, α-lipoic acid; TNPs, titanium dioxide nanoparticles; ROS, reactive oxygen species; SD, standard deviation.

Mentions: To get a closer insight into the possible mechanism of TNP-induced cellular toxicity, the intracellular ROS levels were determined by using the DCFH-DA probe. From Figure 4A and B, we observed the gradually elevated ROS levels in A549 cells in a dose-dependent manner. The generation of ROS in all TNP-treated groups was significantly different with control group. Compared to the group of treatment with TNPs only, the fluorescence intensity of ROS in the group of pretreatment with methyltransferase inhibitor 5-aza was relatively weak (Figure 5A), in line with the effect of ROS scavenger α-LA pretreatment (Figure 5B). It suggested that the methyltransferase inhibitor markedly decreased the generation of ROS induced by TNPs.


Cross talk between poly(ADP-ribose) polymerase 1 methylation and oxidative stress involved in the toxic effect of anatase titanium dioxide nanoparticles.

Bai W, Chen Y, Gao A - Int J Nanomedicine (2015)

Effects of inhibitors, 5-aza or α-LA, on TNP-induced ROS generation in A549 cells.Notes: The methyltransferase inhibitor, 5-aza decreased TNPs-induced ROS generation (A); the antioxidant agent, α-LA suppressed ROS generation triggered by TNPs (B). Data are expressed as mean ± SD; n=5, *P<0.05, compared with control; #P<0.05, compared with TNPs.Abbreviations: 5-aza, 5-aza-2′-deoxycytidine; α-LA, α-lipoic acid; TNPs, titanium dioxide nanoparticles; ROS, reactive oxygen species; SD, standard deviation.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4562766&req=5

f5-ijn-10-5561: Effects of inhibitors, 5-aza or α-LA, on TNP-induced ROS generation in A549 cells.Notes: The methyltransferase inhibitor, 5-aza decreased TNPs-induced ROS generation (A); the antioxidant agent, α-LA suppressed ROS generation triggered by TNPs (B). Data are expressed as mean ± SD; n=5, *P<0.05, compared with control; #P<0.05, compared with TNPs.Abbreviations: 5-aza, 5-aza-2′-deoxycytidine; α-LA, α-lipoic acid; TNPs, titanium dioxide nanoparticles; ROS, reactive oxygen species; SD, standard deviation.
Mentions: To get a closer insight into the possible mechanism of TNP-induced cellular toxicity, the intracellular ROS levels were determined by using the DCFH-DA probe. From Figure 4A and B, we observed the gradually elevated ROS levels in A549 cells in a dose-dependent manner. The generation of ROS in all TNP-treated groups was significantly different with control group. Compared to the group of treatment with TNPs only, the fluorescence intensity of ROS in the group of pretreatment with methyltransferase inhibitor 5-aza was relatively weak (Figure 5A), in line with the effect of ROS scavenger α-LA pretreatment (Figure 5B). It suggested that the methyltransferase inhibitor markedly decreased the generation of ROS induced by TNPs.

Bottom Line: Limited data demonstrated that certain nanomaterials induced the aberrant hypermethylation of PARP-1.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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus