DOI QR코드

DOI QR Code

미세먼지의 di(2-ethylhexyl) phthalate가 유도한 피부상피세포 사멸 신호전달기전 연구

Di(2-ethylhexyl) Phthalate Induces the Apoptotic Cell Death Mediated by Production of Reactive Oxygen Species in Human Keratinocyte

  • 박정배 (대구한의대학교 제약공학과) ;
  • 김지윤 (대구한의대학교 제약공학과) ;
  • 성정희 (리엔젠 부설연구소) ;
  • 김용웅 (대구한의대학교 제약공학과) ;
  • 이세중 (대구한의대학교 제약공학과)
  • Park, Jeong-Bae (Department of Pharmaceutical Engineering, Daegu Haany University) ;
  • Kim, Ji-Yun (Department of Pharmaceutical Engineering, Daegu Haany University) ;
  • Sung, Junghee (R&D center, Reanzen Co.,Ltd.) ;
  • Kim, Yong-ung (Department of Pharmaceutical Engineering, Daegu Haany University) ;
  • Lee, Sei-Jung (Department of Pharmaceutical Engineering, Daegu Haany University)
  • 투고 : 2019.12.13
  • 심사 : 2020.02.12
  • 발행 : 2020.03.31

초록

Particulate matter with an aerodynamic diameter of less than 2.5 μM (PM2.5) is one of the major environmental pollutants. Di(2-ethylhexyl) phthalate (DEHP), an endocrine disrupting chemical in PM2.5, has been utilized for the manufacturing of polyvinyl chloride to increase the flexibility of final products. In the present study, we investigated the ecotoxicological effect of DEHP on the viability of skin keratinocytes (HaCaT). DEHP induced apoptotic cell death mediated by phosphorylation of extracellular signal-regulated kinase through the production of intracellular Reactive Oxygen Species (ROS). Interestingly, we found that DEHP induces the phosphorylation of the nuclear factor-kappa B responsible for the expression of cleaved caspase-3 as an executional cell death protease in HaCaT cells. On the basis of these results, we suggest that DEHP in PM2.5 induces the apoptotic death of human keratinocytes via ROS-mediated signaling events.

키워드

참고문헌

  1. Baeuerle, P. A., Henkel, T., 1994, Function and activation of NF-${\kappa}B$ in the immune system, Annu. Rev. Immunol., 12, 141-179. https://doi.org/10.1146/annurev.iy.12.040194.001041
  2. Bastola, T., An, R. B., Kim, Y. C., Kim, J., Seo, J., 2017, Cearoin induces autophagy, ERK activation and apoptosis via ROS generation in SH-SY5Y neuroblastoma cells, Molecules, 22, 242-255. https://doi.org/10.3390/molecules22020242
  3. Bizon, J. L., LaSarge, C. L., Montgomery, K. S., McDermott, A. N., Setlow, B., Griffith, W. H., 2009, Spatial reference and working memory across the lifespan of male Fischer 344 rats, Neurobiol. Aging, 30, 646-655. https://doi.org/10.1016/j.neurobiolaging.2007.08.004
  4. Christia, C., Poma, G., Harrad, S., de Wit, C. A., Sjostrom, Y., Leonards, P., Lamoree, M., Covaci, A., 2019, Occurrence of legacy and alternative plasticizers in indoor dust from various EU countries and implications for human exposure via dust ingestion and dermal absorption, Environ. Res., 171, 204-212. https://doi.org/10.1016/j.envres.2018.11.034
  5. Cole, M., Lindeque, P., Halsband, C., Galloway, T. S., 2011, Microplastics as contaminants in the marine environment: a review, Mar. Pollut. Bull., 62, 2588-2597. https://doi.org/10.1016/j.marpolbul.2011.09.025
  6. Fan, T. J., Han, L. H., Cong, R. S., Liang, J., 2005, Caspase family proteases and apoptosis, Acta Biochim. Biophys. Sin. (Shanghai), 37, 719-727. https://doi.org/10.1111/j.1745-7270.2005.00108.x
  7. Kim, H. J., Jung, S. K., 2012, New trends in skin barrier research, J. Skin Barrier Research, 14, 15-28.
  8. Kim, K., An, S., Cha, H. J., Choi, Y. M., Choi, S. J., An, I. S., Lee, H. G., Min, Y. H., Lee, S. J., Bae, S., 2013, Lenalidomide induces apoptosis and alters gene expression in non-small cell lung cancer cells, Oncol. Lett., 5, 588-592. https://doi.org/10.3892/ol.2012.1054
  9. Park, J. D., Habeebu, S. S., Klaassen, C. D., 2002, Testicular toxicity of di-(2-ethylhexyl)phthalate in young Sprague-Dawley rats, Toxicology, 171, 105-115. https://doi.org/10.1016/S0300-483X(01)00567-4
  10. Park, J. H., Seo, Y. H., Jang, J. H., Jeong, C. H., Lee, S., Park, B., 2017, Asiatic acid attenuates methamphetamine-induced neuroinflammation and neurotoxicity through blocking of NF-${\kappa}B$/STAT3/ERK and mitochondria-mediated apoptosis pathway, J. Neuroinflammation, 14, 240-255. https://doi.org/10.1186/s12974-017-1009-0
  11. Sidorkiewicz, I., Zareba, K., Wolczynski, S., Czerniecki, J., 2017, Endocrine-disrupting chemicals-Mechanisms of action on male reproductive system, Toxicol. Ind. Health, 33, 601-609. https://doi.org/10.1177/0748233717695160
  12. Son, S., Nam, K., Kim, H., Gye, M. C., Shin, I., 2018, Cytotoxicity measurement of Bisphenol A (BPA) and its substitutes using human keratinocytes, Environ. Res., 164, 655-659. https://doi.org/10.1016/j.envres.2018.03.043
  13. Wier, E. M., Fu, K., Hodgson, A., Sun, X., Wan, F., 2015, Caspase-3 cleaved p65 fragment dampens NF-${\kappa}B$-mediated anti-apoptotic transcription by interfering with the p65/RPS3 interaction, FEBS Lett., 589, 3581-3587. https://doi.org/10.1016/j.febslet.2015.10.019
  14. Yoon, S. D., Baek, W. K., Kim, S. P., Lee, K. S., Cho, J. W., 2013, Induction of apoptosis and autophagy in UVB-treated HaCaT cells, Korean J. Dermatol., 51, 600-607.
  15. Zhang, Y., Han, L., Yang, H., Pang, J., Li, P., Zhang, G., Li, F., Wang, F., 2017, Bisphenol A affects cell viability involved in autophagy and apoptosis in goat testis sertoli cell, Environ. Toxicol. Pharmacol., 55, 137-147. https://doi.org/10.1016/j.etap.2017.07.014
  16. Zhao, J., Tang, C., Nie, X., Xi, H., Jiang, S., Jiang, J., Liu, S., Liu, X., Liang, L., Wan, C., Yang, J., 2016, Autophagy potentially protects against 2,3,7,8-tetrachlorodibenzo-p-Dioxin induced apoptosis in SH-SY5Y cells, Environ. Toxicol., 31, 1068-1079. https://doi.org/10.1002/tox.22116