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EPA attenuates ultraviolet radiation-induced downregulation of aquaporin-3 in human keratinocytes

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Abstract

Eicosapentaenoic acid (EPA) is an omega-3 polyunsaturated fatty acid (ω-3 PUFA) that protects against photodamage and photocarcinogenesis in mammals. Aquaporin-3 (AQP3) is a water/glycerol transport protein that is found in basal layer keratinocytes. In this study, we have investigated the protective effect of EPA against ultraviolet B (UVB)-induced AQP3 downregulation in human keratinocytes. EPA treatment was found to increase AQP3 gene and protein expression in human epidermal keratinocytes (HaCaT). Using a specific inhibitor, we observed that the effect of EPA on AQP3 expression was mediated by extracellular signal-regulated kinase (ERK) activation. UVB radiation induced AQP3 downregulation in HaCaT cells, and it was found that EPA treatment attenuated UVB-induced AQP3 reduction and the associated cell death. UVB-induced downregulation of AQP3 was blocked by EPA and p38 inhibitor SB203580. Collectively, the present results show that EPA increased AQP3 expression and that this led to a reduction UVB-induced photodamage.

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References

  • Bellemère, G., O. Von Stetten, and T. Oddos. 2008. Retinoic acid increases aquaporin 3 expression in normal human skin. Journal of Investigative Dermatology 128: 542–548.

    PubMed  Google Scholar 

  • Blok, W.L., M.B. Katan, and J.W. van der Meer. 1996. Modulation of inflammation and cytokine production by dietary (n-3) fatty acids. Journal of Nutrition 126(6): 1513–1533.

    Google Scholar 

  • Calder, P.C. 2001. N-3 polyunsaturated fatty acids, inflammation and immunity: pouring oil on troubled waters or another fishy tale? Nutrition Research 21: 309–314.

    Article  CAS  Google Scholar 

  • Calder, P.C. 2006. Polyunsaturated fatty acids and inflammation. Prostaglandins Leukotrienes and Essential Fatty Acids 75: 197–202.

    Article  CAS  Google Scholar 

  • Cao, C., S. Wan, Q. Jiang, A. Amaral, S. Lu, G. Hu, Z. Bi, N. Kouttab, W. Chu, and Y. Wan. 2007. All-trans retinoic acid attenuates ultraviolet radiation-induced down-regulation of aquaporin-3 and water permeability in human keratinocytes. Journal of Cellular Physiology 215: 506–516.

    Article  Google Scholar 

  • Fisher, G.J., S. Datta, Z. Wang, X.Y. Li, T. Quan, J.H. Chung, S. Kang, and J.J. Voorhees. 2000. c-jun-dependent inhibition of cutaneous procollagen transcription following ultraviolet irradiation is reversed by all-trans retinoic acid. Journal of Clinical Investigation 106: 663–670.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Gruijl, F.R., and L. Van. 1994. Estimate of the wavelength dependency of ultraviolet carcinogenesis in humans and its relevance to the risk assessment of a stratospheric ozone depletion. Health Physics 67: 319–325.

    Article  PubMed  Google Scholar 

  • Hara, M., and A.S. Verkman. 2003. Glycerol replacement corrects defective skin hydration, elasticity, and barrier function in aquaporin-3-deficient mice. Proceedings of the National Academy of Sciences of the United States of America 100: 7360–7365.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hara-Chikuma, M., and A.S. Verkman. 2005. Aquaporin-3 functions as a glycerol transporter in mammalian skin. Biology of the Cell 97: 479–486.

    Article  CAS  PubMed  Google Scholar 

  • Hatakeyama, S., Y. Yoshida, T. Tani, Y. Koyama, K. Nihei, K. Ohshiro, J.I. Kamiie, E. Yaoita, T. Suda, K. Hatakeyama, and T. Yamamoto. 2001. Cloning of a new aquaporin (AQP 10) abundantly expressed in duodenum and jejunum. Biochemical and Biophysical Research Communications 287: 814–819.

    Article  CAS  PubMed  Google Scholar 

  • Ji, C., C. Cao, S. Lu, R. Kivlin, A. Amaral, N. Kouttab, H. Yang, W. Chu, Z. Bi, W. Di, and Y. Wan. 2008. Curcumin attenuates EGF-induced AQP3 up-regulation and cell migration in human ovarian cancer cells. Cancer Chemotherapy and Pharmacology 62: 857–865.

    Article  CAS  PubMed  Google Scholar 

  • Ji, C., Y. Yang, B. Yang, J. Xia, W. Sun, Z. Su, L. Yu, S. Shan, S. He, L. Cheng, Y. Wan, and Z. Bi. 2010. Trans-Zeatin attenuates ultraviolet induced down-regulation of aquaporin-3 in cultured human skin keratinocytes. International Journal of Molecular Medicine 26: 257–263.

    CAS  PubMed  Google Scholar 

  • Kang, S., J.H. Chung, J.H. Lee, G.J. Fisher, Y.S. Wan, E.A. Duell, and J.J. Voorhees. 2003. Topical N-acetyl cysteine and genistein prevent ultraviolet-light-induced signaling that leads to photoaging in human skin in vivo. Journal of Investigative Dermatology 120: 835–841.

    Article  CAS  PubMed  Google Scholar 

  • Katiyar, S.K., F. Afaq, K. Azizuddin, and H. Mukhtar. 2001. Inhibition of UVB-induced oxidative stress-mediated phosphorylation of mitogen-activated protein kinase signaling pathways in cultured human epidermal keratinocytes by green tea polyphenol (-)-epigallocatechin-3-gallate. Toxicology and Applied Pharmacology 176: 110–117.

    Article  CAS  PubMed  Google Scholar 

  • Li, J., H. Tang, X. Hu, M. Chen, and H. Xie. 2010. Aquaporin-3 gene and protein expression in sun-protected human skin decreases with skin ageing. Australasian Journal of Dermatology 51: 106–112.

    Article  PubMed  Google Scholar 

  • Ma, T., M. Hara, R. Sougrat, R. Sougrat, J.M. Verbavatz, and A.S. Verkman. 2002. Impaired stratum corneum hydration in mice lacking epidermal water channel aquqporin-3. Journal of Biological Chemistry 277: 17147–17153.

    Article  CAS  PubMed  Google Scholar 

  • Matsuzaki, T., T. Suzuki, H. Koyama, H. Koyama, S. Tanaka, and K. Takata. 1999. Water channel protein AQP3 is present in epithelia exposed to the environment of possible water loss. Journal of Histochemistry and Cytochemistry 47: 1275–1286.

    Article  CAS  PubMed  Google Scholar 

  • Mayser, P., H. Grimm, and F. Grimminger. 2002. n-3 fatty acids in psoriasis. British Journal of Nutrition 87: 77–82.

    Article  Google Scholar 

  • Morishita, Y., Y. Sakube, S. Sasaki, and K. Ishibashi. 2004. Molecular mechanisms and drug development in aquaporin water channel diseases: aquaporin superfamily (superaquaporins): expansion of aquaporins restricted to multicellular organisms. Journal of Pharmacological Sciences 96: 276–279.

    Article  CAS  PubMed  Google Scholar 

  • Nakakoshi, M., Y. Morishita, K. Usui, M. Ohtsuki, and K. Ishibashi. 2006. Identification of a keratinocarcinoma cell line expressing AQP3. Biology of the Cell 98: 95–100.

    Article  CAS  PubMed  Google Scholar 

  • Olsson, M., A. Broberg, M. Jernås, L. Carlsson, M. Rudemo, M. Suurkula, P.A. Svensson, and M. Benson. 2006. Increased expression of aquaporin 3 in atopic eczema. Allergy 61: 1132–1137.

    Article  CAS  PubMed  Google Scholar 

  • Rhodes, L.E., H. Shahbakhti, R.M. Azurdia, R.M. Moison, M.J. Steenwinkel, M.I. Homburg, M.P. Dean, M.P. McArdle, G.M.B. van Henegouwen, B. Epe, and A.A. Vink. 2003. Effect of eicosapentaenoic acid, an omega-3 polyunsaturated fatty acid, on UVR-related cancer risk in humans. An assessment of early genotoxic markers. Carcinogenesis 24: 919–925.

    Article  CAS  PubMed  Google Scholar 

  • Shan, S.J., T. Xiao, J. Chen, S.L. Geng, C.P. Li, X. Xu, Y. Hong, C. Ji, Y. Guo, H. Wei, W. Liu, D. Li, and H.D. Chen. 2012. Kanglaite attenuates UVB-induced down-regulation of aquaporin-3 in cultured human skin keratinocytes. International Journal of Molecular Medicine 29: 625–629.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Song, X., A. Xu, W. Pan, B. Wallin, R. Kivlin, S. Lu, C. Cao, Z. Bi, and Y. Wan. 2008. Nicotinamide attenuates aquaporin 3 overexpression induced by retinoic acid through inhibition of EGFR/ERK in cultured human skin keratinocytes. International Journal of Molecular Medicine 22: 229–236.

    CAS  PubMed  Google Scholar 

  • Sougrat, R., M. Morand, C. Gondran, P. Barre, R. Gobin, F. Bonte, M. Dumas, and J.M. Verbavatz. 2002. Functional expression of AQP3 in human skin epidermis and reconstructed epidermis. Journal of Investigative Dermatology 118: 678–685.

    Article  CAS  PubMed  Google Scholar 

  • Storey, A., F. McArdle, P.S. Friedmann, M.J. Jackson, and L.E. Rhodes. 2005. Eicosapentaenoic acid and docosahexaenoic acid reduce UVB- and TNF-alpha-induced IL-8 secretion in keratinocytes and UVB-induced IL-8 in fibroblasts. Journal of Investigative Dermatology 124: 248–255.

    Article  CAS  PubMed  Google Scholar 

  • Verkman, A.S., and A.K. Mitra. 2000. Structure and function of aquaporin water channel. American Journal of Physiology Renal Physiology 278: F13–F28.

    CAS  PubMed  Google Scholar 

  • Wu, Z., H. Uchi, S. Morino-Koga, W. Shi, and M. Furue. 2014. Resveratrol inhibition of human keratinocyte proliferation via SIRT1/ARNT/ERK dependent downregulation of aquaporin 3. The Journal of Dermatological Science 75: 16–23.

    Article  CAS  PubMed  Google Scholar 

  • Wolters, M. 2005. Diet and psoriasis: experimental data and clinical evidence. British Journal of Dermatology 153: 706–714.

    Article  CAS  PubMed  Google Scholar 

  • Xie, H., F. Liu, L. Liu, J. Dan, Y. Luo, Y. Yi, X. Chen, and J. Li. 2013. Protective role of AQP3 in UVA-induced NHSFs apoptosis via Bcl2 up-regulation. Archives of Dermatological Research 305: 397–406.

    Article  CAS  PubMed  Google Scholar 

  • Xue, H., M. Wan, D. Song, Y. Li, and J. Li. 2006. Eicosapentaenoic acid and docosahexaenoic acid modulate mitogen-activated protein kinase activity in endothelium. Vascular Pharmacology 44: 434–439.

    Article  CAS  PubMed  Google Scholar 

  • Zelenina, M., and H. Brismar. 2000. Osmotic water permeability measurements using confocal laser scanning microscopy. European Biophysics Journal 29: 165–171.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by a Grant of the Korea Healthcare technology R&D Project, Ministry of Health & Welfare [No. 103017] and by the National Research Foundation of Korea grant funded by the Korea government [No. 2008-0062484].

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Correspondence to Yeun-Ja Mun.

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Jeon, BK., Kang, MK., Lee, GT. et al. EPA attenuates ultraviolet radiation-induced downregulation of aquaporin-3 in human keratinocytes. Arch. Pharm. Res. 38, 1552–1560 (2015). https://doi.org/10.1007/s12272-014-0482-6

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  • DOI: https://doi.org/10.1007/s12272-014-0482-6

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