Abstract
Aquaporin-3 (AQP3), a water/glycerol-transporting protein that facilitates water, urea, and glycerol transport, can inhibit arsenite-induced apoptosis by up-regulating Bcl-2. However, whether it has a protective role in ultraviolet A (UVA)-induced apoptosis in normal human skin fibroblasts is not known. In this study, we demonstrate that mild UVA treatment fails to induce oxidative cell stress and apoptosis in normal human skin fibroblasts (NHSFs) overexpressing AQP3. After severe UVA irradiation, there was an increase in oxidative cell stress and apoptosis when AQP3 levels decreased. We also found that silencing AQP3 sensitized NHSFs to low-dose UVA. Overexpressing AQP3 was protective against high-dose UVA-induced oxidative stress and apoptosis. Besides, we observed that Bcl-2 may be involved in UVA-induced apoptosis. Our findings suggested that the water/glycerol-transporting protein AQP3 plays a role in resistance to UVA-induced apoptosis.
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Benhamou PY, Moriscot C, Richard MJ, Kerr-Conte J, Pattou F, Chroboczek J, Lemarchand P, Halimi S (1998) Adenoviral-mediated catalase gene transfer protects porcine and human islets in vitro against oxidative stress. Transplant Proc 30:459
Bienert GP, Moller AL, Kristiansen KA, Schulz A, Moller IM, Schjoerring JK, Jahn TP (2007) Specific aquaporins facilitate the diffusion of hydrogen peroxide across membranes. J Biol Chem 282:1183–1192
Boyer JZ, Jandova J, Janda J, Vleugels FR, Elliott DA, Sligh JE (2012) Resveratrol-sensitized UVA induced apoptosis in human keratinocytes through mitochondrial oxidative stress and pore opening. J Photochem Photobiol B 113:42–50
Cao C, Sun Y, Healey S, Bi Z, Hu G, Wan S, Kouttab N, Chu W, Wan Y (2006) EGFR-mediated expression of aquaporin-3 is involved in human skin fibroblast migration. Biochem J 400:225–234
Cao C, Wan S, Jiang Q, Amaral A, Lu S, Hu G, Bi Z, Kouttab N, Chu W, Wan Y (2008) All-trans retinoic acid attenuates ultraviolet radiation-induced down-regulation of aquaporin-3 and water permeability in human keratinocytes. J Cell Physiol 215:506–516
Das J, Sil PC (2012) Taurine ameliorates alloxan-induced diabetic renal injury, oxidative stress-related signaling pathways and apoptosis in rats. Amino Acids 43:1509–1523
Favaloro B, Allocati N, Graziano V, Di Ilio C, De Laurenzi V (2012) Role of apoptosis in disease. Aging 4:330–349
Gao L, Gao Y, Li X, Howell P, Kumar R, Su X, Vlassov AV, Piazza GA, Riker AI, Sun D, Xi Y (2012) Aquaporins mediate the chemoresistance of human melanoma cells to arsenite. Mol Oncol 6:81–87
Gehrmann W, Elsner M, Lenzen S (2010) Role of metabolically generated reactive oxygen species for lipotoxicity in pancreatic beta-cells. Diabetes Obes Metab 12(Suppl 2):149–158
Haldar S, Jena N, Croce CM (1995) Inactivation of Bcl-2 by phosphorylation. Proc Natl Acad Sci USA 92:4507–4511
Hara-Chikuma M, Verkman AS (2005) Aquaporin-3 functions as a glycerol transporter in mammalian skin. Biol Cell 97:479–486
Heinen RB, Ye Q, Chaumont F (2009) Role of aquaporins in leaf physiology. J Exp Bot 60:2971–2985
Hseu YC, Chou CW, Senthil Kumar KJ, Fu KT, Wang HM, Hsu LS, Kuo YH, Wu CR, Chen SC, Yang HL (2012) Ellagic acid protects human keratinocyte (HaCaT) cells against UVA-induced oxidative stress and apoptosis through the upregulation of the HO-1 and Nrf-2 antioxidant genes. Food Chem Toxicol 50:1245–1255
Ishibashi K (2009) New members of mammalian aquaporins: AQP10–AQP12. Handb Exp Pharmacol 190:251–262
Ishibashi K, Hara S, Kondo S (2009) Aquaporin water channels in mammals. Clin Exp Nephrol 13:107–117
Ismail M, Bokaee S, Morgan R, Davies J, Harrington KJ, Pandha H (2009) Inhibition of the aquaporin 3 water channel increases the sensitivity of prostate cancer cells to cryotherapy. Br J Cancer 100:1889–1895
Ito T, Deng X, Carr B, May WS (1997) Bcl-2 phosphorylation required for anti-apoptosis function. J Biol Chem 272:11671–11673
Ji C, Yang Y, Yang B, Xia J, Sun W, Su Z, Yu L, Shan S, He S, Cheng L, Wan Y, Bi Z (2010) Trans-Zeatin attenuates ultraviolet induced down-regulation of aquaporin-3 in cultured human skin keratinocytes. Int J Mol Med 26:257–263
Kanamaru Y, Sekine S, Ichijo H, Takeda K (2012) The phosphorylation-dependent regulation of mitochondrial proteins in stress responses. J Signal Transduct 2012:931215
Kehrer JP (1993) Free radicals as mediators of tissue injury and disease. Crit Rev Toxicol 23:21–48
Kelekar A, Thompson CB (1998) Bcl-2-family proteins: the role of the BH3 domain in apoptosis. Trends Cell Biol 8:324–330
King LS, Kozono D, Agre P (2004) From structure to disease: the evolving tale of aquaporin biology. Nat Rev Mol Cell Biol 5:687–698
Klotz LO, Holbrook NJ, Sies H (2001) UVA and singlet oxygen as inducers of cutaneous signaling events. Curr Probl Dermatol 29:95–113
Krane CM, Goldstein DL (2007) Comparative functional analysis of aquaporins/glyceroporins in mammals and anurans. Mamm Genome 18:452–462
Kultz D, Burg MB (1998) Intracellular signaling in response to osmotic stress. Contrib Nephrol 123:94–109
Kutuk O, Letai A (2008) Regulation of Bcl-2 family proteins by posttranslational modifications. Curr Mol Med 8:102–118
Li J, Tang H, Hu X, Chen M, Xie H (2010) Aquaporin-3 gene and protein expression in sun-protected human skin decreases with skin ageing. Australas J Dermatol 51:106–112
Lin HI, Lee YJ, Chen BF, Tsai MC, Lu JL, Chou CJ, Jow GM (2005) Involvement of Bcl-2 family, cytochrome c and caspase 3 in induction of apoptosis by beauvericin in human non-small cell lung cancer cells. Cancer Lett 230:248–259
Liu H, Wintour EM (2005) Aquaporins in development—a review. Reprod Biol Endocrinol 3:18
Loreto C, Reggio E (2010) Aquaporin and vascular diseases. Curr Neuropharmacol 8:105–111
Matsumura Y, Ananthaswamy HN (2004) Toxic effects of ultraviolet radiation on the skin. Toxicol Appl Pharmacol 195:298–308
Maverakis E, Miyamura Y, Bowen MP, Correa G, Ono Y, Goodarzi H (2010) Light, including ultraviolet. J Autoimmun 34:J247–J257
McBride HM, Neuspiel M, Wasiak S (2006) Mitochondria: more than just a powerhouse. Curr Biol 16:R551–R560
Pustisek N, Situm M (2011) UV-radiation, apoptosis and skin. Coll Antropol 35(Suppl 2):339–341
Rathmell JC, Thompson CB (2002) Pathways of apoptosis in lymphocyte development, homeostasis, and disease. Cell 109(Suppl):S97–S107
Raval CM, Zhong JL, Mitchell SA, Tyrrell RM (2012) The role of Bach1 in ultraviolet A-mediated human heme oxygenase 1 regulation in human skin fibroblasts. Free Radic Biol Med 52:227–236
Rezvani HR, Mazurier F, Cario-Andre M, Pain C, Ged C, Taieb A, de Verneuil H (2006) Protective effects of catalase overexpression on UVB-induced apoptosis in normal human keratinocytes. J Biol Chem 281:17999–18007
Rieux-Laucat F, Fischer A, Deist FL (2003) Cell-death signaling and human disease. Curr Opin Immunol 15:325–331
Ryter SW, Kim HP, Hoetzel A, Park JW, Nakahira K, Wang X, Choi AM (2007) Mechanisms of cell death in oxidative stress. Antioxid Redox Signal 9:49–89
Shan SJ, Xiao T, Chen J, Geng SL, Li CP, Xu X, Hong Y, Ji C, Guo Y, Wei H, Liu W, Li D, Chen HD (2012) Kanglaite attenuates UVB-induced down-regulation of aquaporin-3 in cultured human skin keratinocytes. Int J Mol Med 29:625–629
Thiagarajah JR, Zhao D, Verkman AS (2007) Impaired enterocyte proliferation in aquaporin-3 deficiency in mouse models of colitis. Gut 56:1529–1535
Tyrrell RM (1996) UV activation of mammalian stress proteins. EXS 77:255–271
Wang X (2001) The expanding role of mitochondria in apoptosis. Genes Dev 15:2922–2933
Xu B, Moritz JT, Epstein PN (1999) Overexpression of catalase provides partial protection to transgenic mouse beta cells. Free Radic Biol Med 27:830–837
Yamamoto K, Ichijo H, Korsmeyer SJ (1999) BCL-2 is phosphorylated and inactivated by an ASK1/Jun N-terminal protein kinase pathway normally activated at G(2)/M. Mol Cell Biol 19:8469–8478
Youle RJ, Strasser A (2008) The BCL-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Cell Biol 9:47–59
Zhou BR, Yin HB, Xu Y, Wu D, Zhang ZH, Yin ZQ, Permatasari F, Luo D (2012) Baicalin protects human skin fibroblasts from ultraviolet A radiation-induced oxidative damage and apoptosis. Free Radic Res 46:1458–1471
Acknowledgments
The study was supported by the National Natural Science Foundation of China (NO. 81271775, 81171520), the Research Fund for the Doctoral Program of Higher Education of China (RFDP) (20100162110035), the China Postdoctoral Science Foundation (2012M511421), the Scientific Research Fund of Hunan Provincial Science and Technology Department (2012WK3045).
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The authors declare that they have no competing interests.
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F. Liu and H. Xie are the co-first authors.
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Xie, H., Liu, F., Liu, L. et al. Protective role of AQP3 in UVA-induced NHSFs apoptosis via Bcl2 up-regulation. Arch Dermatol Res 305, 397–406 (2013). https://doi.org/10.1007/s00403-013-1324-y
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DOI: https://doi.org/10.1007/s00403-013-1324-y