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MicroRNA expression profiling of p-phenylenediamine treatment in human keratinocyte cell line

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Abstract

p-Phenylenediamine (PPD), a black dye used in hair coloring and tattoos, irritates the skin, leading to cell cycle arrest, apoptosis, and reactive oxygen species (ROS) generation. MicroRNAs (miRNAs) are well known regulators of these side effects. The aim of the present study was to evaluate PPD-induced miRNA expression profile alterations in human keratinocytes. First, we demonstrated that PPD reduced HaCaT cell viability by inducing cell cycle arrest and death, elevating cellular ROS levels and decreasing the migration rate. In addition, 67 miRNAs were upregulated by at least 5-fold in PPD-treated HaCaT cell and 17 miRNAs were downregulated by at least 5- fold in PPD-treated HaCaT cell. Using bioinformatics, we identified a relationship between PPD-mediated miRNA changes and cell death, cell cycle arrest, generation of ROS, and migration repression. Target genes of PPD-regulated miRNAs were involved in cell proliferation, apoptosis, skin development, and aging. Thus, our results establish a role for miRNAs in regulating PPD-induced cell death, cell cycle arrest, ROS generation, and repression of migration in human keratinocytes.

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References

  1. Lawrence, N. S., Beckett, E. L., Davis, J. & Comptonm, R.G. Voltammetric investigation of hair dye constituents: application to the quantification of p-phenylenediamine. Analyst 126:1897–900 (2001).

    Article  CAS  PubMed  Google Scholar 

  2. Corbett, J. F. An historical review of the use of dye precursors in the formulation of commercial oxidation hair dyes. Dyes Pigments 41:127–136 (1999).

    Article  CAS  Google Scholar 

  3. Brown, K. C. in Hair and Hair Care (eds Johnson, D.) 191–215 (Marcel Dekker, New York, 1997).

  4. Gendler, E. Adverse reaction to cosmetics. Cutis 39: 525–526 (1987).

    CAS  PubMed  Google Scholar 

  5. Moeller, R., Lichter, J. & Blömeke, B. Impact of paraphenylenediamine on cyclooxygenases expression and prostaglandin formation in human immortalized keratinocytes (HaCaT). Toxicology 249:167–175 (2008).

    Article  CAS  PubMed  Google Scholar 

  6. Eilstein, J., Giménez-Arnau, E., Duché, D., Rousset, F. & Lepoittevin, J. P. Mechanistic studies on the lysine-induced N-formylation of 2,5-dimethyl-p-benzoquinonediimine. Chem Res Toxicol 20:1155–1161 (2007).

    Article  CAS  PubMed  Google Scholar 

  7. McFadden, J. P., Yeo, L. & White, J. L. Clinical and experimental aspects of allergic contact dermatitis to para-phenylenediamine. Clin Dermatol 29:316–324 (2011).

    Article  PubMed  Google Scholar 

  8. So, J. Y., Shin, C. Y., Song, M., Rha, Y. A. & Ryu, J. C. Gene expression profiling of hair-dying agent, paraphenylenediamine, in human keratinocytes (HaCaT) cells. Mol Cell Toxicol 7:339–346 (2011).

    Article  CAS  Google Scholar 

  9. Moeller, R., Lichter, J. & Blömeke, B. Impact of paraphenylenediamine on cyclooxygenases expression and prostaglandin formation in human immortalized keratinocytes (HaCaT). Toxicology 249:167–175 (2008).

    Article  CAS  PubMed  Google Scholar 

  10. Chung, K. T. et al. Mutagenicity and toxicity studies of p-phenylenediamine and its derivatives. Toxicol Lett 81:23–32 (1995).

    Article  CAS  PubMed  Google Scholar 

  11. Chye, S. M. et al. Apoptosis induced by para-phenylenediamine involves formation of ROS and activation of p38 and JNK in chang liver cells. Environ Toxicol 29:981–990 (2014).

    Article  CAS  PubMed  Google Scholar 

  12. Sontheimer, E. J. & Carthew, R. W. Silence from within: endogenous siRNAs and miRNAs. Cell 122:9–12 (2005).

    Article  CAS  PubMed  Google Scholar 

  13. Hooff, G. P. et al. Analytical Investigations of Toxic p-Phenylenediamine (PPD) Levels in Clinical Urine Samples with Special Focus on MALDI-MS/MS. PLoS One 6:e22191 (2011).

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Tsutsumi, S. et al. Gastric irritant-induced apoptosis in guinea pig gastric mucosal cells in primary culture. Biochim Biophys Acta 1589:168–180 (2002).

    Article  CAS  PubMed  Google Scholar 

  15. Nakai, K., Yoneda, K. & Kubota, Y. Oxidative stress in allergic and irritant dermatitis: from basic research to clinical management. Recent Pat Inflamm Allergy Drug Discov 6:202–209 (2012).

    Article  CAS  PubMed  Google Scholar 

  16. Jovanovic, M. & Hengartner, M. O. miRNAs and apoptosis: RNAs to die for. Oncogene 25:6176–6187, (2006).

    Article  CAS  PubMed  Google Scholar 

  17. Bueno, M. J. & Malumbres, M. MicroRNAs and the cell cycle. Biochim Biophys Acta 1812: 592–601 (2011).

    Article  CAS  PubMed  Google Scholar 

  18. Xu, S. et al. Oxidative stress mediated-alterations of the microRNA expression profile in mouse hippocampal neurons. Int J Mol Sci 13:16945–16960 (2012).

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Cui, L. et al. MicroRNA-99a induces G1-phase cell cycle arrest and suppresses tumorigenicity in renal cell carcinoma. BMC Cancer 12:546 (2012).

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Liu, Q. et al. miR-16 family induces cell cycle arrest by regulating multiple cell cycle genes. Nucleic Acids Res 36:5391–5404 (2008).

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Cimmino, A. et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A 102:13944–13949 (2005).

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Zhang, X. et al. MicroRNA-21 modulates the levels of reactive oxygen species levels by targeting SOD3 and TNFa. Cancer Res 72:4707–4713 (2012).

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. An, Y. R. & Hwang, S. Y. Toxicology study with microRNA. Mol Cell Toxicol 10:127–134 (2014).

    Article  CAS  Google Scholar 

  24. Lema, C. & Cunningham, M. J. MicroRNAs and their implications in toxicological research. Toxicol Lett 5:100–105 (2010).

    Article  Google Scholar 

  25. Chen, S. C. et al. p-Phenylenediamine induces p.53- mediated apoptosis in Mardin Darby canine Kidney cells. Toxicol In Vitro 20:801–807 (2006).

    Article  CAS  PubMed  Google Scholar 

  26. Chen, S. C. et al. Para-phenylenediamine induced DNA damage and apoptosis through oxidative stress and enhanced caspase-8 and-9 activities in Mardin-Darby canine kidney cells. Toxicol In Vitro 24:1197–1202 (2010).

    Article  CAS  PubMed  Google Scholar 

  27. Ohdaira, H., Sekiguchi, M., Miyata, K. & Yoshida, K. MicroRNA-494 suppresses cell proliferation and induces senescence in A549 lung cancer cells. Cell Prolif 45:32–38 (2012).

    Article  CAS  PubMed  Google Scholar 

  28. Romano, G. et al. MiR-494 is regulated by ERK1/2 and modulates TRAIL-induced apoptosis in non-smallcell lung cancer through BIM down-regulation. Proc Natl Acad Sci U S A 109:16570–16575 (2012).

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Saini, S. et al. MicroRNA-708 induces apoptosis and suppresses tumorigenicity in renal cancer cells. Cancer Res 71:6208–6219 (2011).

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Wada, T. & Penninger, J. M. Mitogen-activated protein kinases in apoptosis regulation. Oncogene 23: 2838–2849 (2004).

    Article  CAS  PubMed  Google Scholar 

  31. Zhang, W. & Liu, H. T. MAPK signal pathways in the regulation of cell proliferation in mammalian cells. Cell Res 12:9–18 (2002).

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Seunghee Bae.

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Cha, H.J., Lee, OK., Kim, S.Y. et al. MicroRNA expression profiling of p-phenylenediamine treatment in human keratinocyte cell line. Mol. Cell. Toxicol. 11, 19–28 (2015). https://doi.org/10.1007/s13273-015-0003-9

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  • DOI: https://doi.org/10.1007/s13273-015-0003-9

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