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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 methylation of PARP-1 by MSP in A549 cells.Notes: Treatment with methyltransferase inhibitor, 5-aza (A); treatment with antioxidant agent, α-LA (B). U and M: primer sets specific to unmethylated (U) and methylated (M) DNA molecules. The data were typical examples of five independent experiments. *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; PARP-1, poly(ADP-ribose) polymerase 1; MSP, methylation-specific PCR; PCR, polymerase chain reaction.
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f7-ijn-10-5561: Effects of inhibitors, 5-aza or α-LA, on TNP-induced methylation of PARP-1 by MSP in A549 cells.Notes: Treatment with methyltransferase inhibitor, 5-aza (A); treatment with antioxidant agent, α-LA (B). U and M: primer sets specific to unmethylated (U) and methylated (M) DNA molecules. The data were typical examples of five independent experiments. *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; PARP-1, poly(ADP-ribose) polymerase 1; MSP, methylation-specific PCR; PCR, polymerase chain reaction.

Mentions: MSP, a common detection method of methylation, was performed to analyze the methylation status of PARP-1. Our results revealed that TNPs notably elevated the level of PARP-1 methylation in a dose-dependent way (Figure 6). However, pretreatment of both methyltransferase inhibitor 5-aza and ROS scavenger α-LA inversely altered the TNP-induced hypermethylation of PARP-1 promoter region (Figure 7A and B), implicating that the antioxidant agent α-LA decreased TNP-induced ROS generation and simultaneously attenuated TNP-triggered PARP-1 hypermethylation.


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 methylation of PARP-1 by MSP in A549 cells.Notes: Treatment with methyltransferase inhibitor, 5-aza (A); treatment with antioxidant agent, α-LA (B). U and M: primer sets specific to unmethylated (U) and methylated (M) DNA molecules. The data were typical examples of five independent experiments. *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; PARP-1, poly(ADP-ribose) polymerase 1; MSP, methylation-specific PCR; PCR, polymerase chain reaction.
© Copyright Policy
Related In: Results  -  Collection

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

f7-ijn-10-5561: Effects of inhibitors, 5-aza or α-LA, on TNP-induced methylation of PARP-1 by MSP in A549 cells.Notes: Treatment with methyltransferase inhibitor, 5-aza (A); treatment with antioxidant agent, α-LA (B). U and M: primer sets specific to unmethylated (U) and methylated (M) DNA molecules. The data were typical examples of five independent experiments. *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; PARP-1, poly(ADP-ribose) polymerase 1; MSP, methylation-specific PCR; PCR, polymerase chain reaction.
Mentions: MSP, a common detection method of methylation, was performed to analyze the methylation status of PARP-1. Our results revealed that TNPs notably elevated the level of PARP-1 methylation in a dose-dependent way (Figure 6). However, pretreatment of both methyltransferase inhibitor 5-aza and ROS scavenger α-LA inversely altered the TNP-induced hypermethylation of PARP-1 promoter region (Figure 7A and B), implicating that the antioxidant agent α-LA decreased TNP-induced ROS generation and simultaneously attenuated TNP-triggered PARP-1 hypermethylation.

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