Mitochondrial Dysfunction and Tissue Alterations of Ultraviolet-Irradiated Skin in Five Different Mice Strains
DOI:
https://doi.org/10.12970/2310-998X.2014.02.01.2Keywords:
Mitochondrial function, Inflammation, UV irradiation, epidermis, keratinocytes.Abstract
Ultraviolet radiation (UVR) effects on skin have been extensively studied. Several mice strains have been used worldwide in photobiology and photoimmunology studies. Recently, we have developed a method based on flow cytometry in order to analyze mitochondrial dysfunction and superoxide (O2•-) production ex vivo in keratinocytes isolated from irradiated-mice. This method can be helpful to evaluate mitochondrial alterations in different mice models.
In this work, we aimed to compare epidermal response to UVR in five mice strains, both pigmented and albino as well as hairy and hairless strains (SKH:1, Balb/c, C57/BL, DBA/2N and Swiss). Keratinocytes mitochondrial alterations, epidermal hyperplasia and inflammatory mediators’ production (epidermis and serum) were determined 72 hours after a 400 mJ/cm2 UV dose.
All strains showed epidermal hyperplasia and loss of mitochondrial polarization after irradiation, differing in the magnitude of the response. However, there were significant differences in the basal mitochondrial polarization between strains, showing that the metabolic state of keratinocytes may vary between them. Moreover, mitochondrial O2•- production was induced in SKH:1 and Balb/c after irradiation, whereas in DBA/2N, Swiss and C57/BL it was at the same level or even lower than in the non-irradiated control. Finally, an increase in inflammatory mediators was only detected in the serum of C57/BL and Swiss mice and in the epidermis of DBA/2N and C57/BL.
Results show that each mice strain has particular characteristics related to cellular metabolism, which may lead to particular responses to UVR exposure. Therefore, the use of a particular mice strain in photobiology models should be carefully considered.
References
Gibbs NK, Norval M. Urocanic acid in the skin: a mixed blessing? J Invest Dermatol 2011; 131: 14-7. http://dx.doi.org/10.1038/jid.2010.276
Lee J. Molecular events associated with apoptosis and proliferation induced by ultraviolet-B radiation in the skin of hairless mice. J Dermatol Sci 2003; 32: 171-9. http://dx.doi.org/10.1016/S0923-1811(03)00094-X
Tada-Oikawa S, Oikawa S, Kawanishi S. Role of ultraviolet A-induced oxidative DNA damage in apoptosis via loss of mitochondrial membrane potential and caspase-3 activation. Biochem Biophys Res Commun 1998; 247: 693-6. http://dx.doi.org/10.1006/bbrc.1998.8869
Henseleit U, Rosenbach T, Kolde G. Induction of apoptosis in human HaCaT keratinocytes. Arch Dermatol Res 1996; 288: 676-83. http://dx.doi.org/10.1007/BF02505277
Gonzalez Maglio DH, Paz ML, Ferrari A, et al. Skin damage and mitochondrial dysfunction after acute ultraviolet B irradiation: relationship with nitric oxide production. Photodermatol Photoimmunol Photomed 2005; 21: 311-7. http://dx.doi.org/10.1111/j.1600-0781.2005.00185.x
Paz ML, González Maglio DH, Weill FS, Bustamante J, Leoni J. Mitochondrial dysfunction and cellular stress progression after ultraviolet B irradiation in human keratinocytes. Photodermatol Photoimmunol Photomed 2008; 24: 115-22. http://dx.doi.org/10.1111/j.1600-0781.2008.00348.x
Assefa Z, Vantieghem A, Garmyn M, et al. p38 mitogen-activated protein kinase regulates a novel, caspase-independent pathway for the mitochondrial cytochrome c release in ultraviolet B radiation-induced apoptosis. J Biol Chem 2000; 275: 21416-21. http://dx.doi.org/10.1074/jbc.M002634200
Nicolò C, Tomassini B, Rippo MR, Testi R. UVB-induced apoptosis of human dendritic cells: contribution by caspase-dependent and caspase-independent pathways. Blood 2001; 97: 1803-8. http://dx.doi.org/10.1182/blood.V97.6.1803
Chen AC, Halliday GM, Damian DL. Non-melanoma skin cancer: carcinogenesis and chemoprevention. Pathology 2013; 45: 331-41. http://dx.doi.org/10.1097/PAT.0b013e32835f515c
Kim KH, Park EJ, Seo YJ, et al. Immunohistochemical study of cyclooxygenase-2 and p53 expression in skin tumors. J Dermatol 2006; 33: 319-25. http://dx.doi.org/10.1111/j.1346-8138.2006.00076.x
Gonzalez Maglio DH, Cela EM, Ferrari A, Leoni J. Mitochondrial function evaluation in epidermal cells ex vivo after ultraviolet irradiation. Exp Dermatol 2011; 20: 947-50. http://dx.doi.org/10.1111/j.1600-0625.2011.01342.x
Paz ML, Ferrari A, Weill FS, Leoni J, Gonzalez Maglio DH. Time-course evaluation and treatment of skin inflammatory immune response after ultraviolet B irradiation. Cytokine 2008; 44: 70-7. http://dx.doi.org/10.1016/j.cyto.2008.06.012
Köck A, Schwarz T, Kirnbauer R, et al. Human keratinocytes are a source for tumor necrosis factor alpha: evidence for synthesis and release upon stimulation with endotoxin or ultraviolet light. J Exp Med 1990; 172: 1609-14. http://dx.doi.org/10.1084/jem.172.6.1609
Harrison GI, Young AR. Ultraviolet radiation-induced erythema in human skin. Methods 2002; 28: 14-9. http://dx.doi.org/10.1016/S1046-2023(02)00205-0
Pennello G, Devesa S, Gail M. Association of Surface Ultraviolet B Radiation Levels with Melanoma and Nonmelanoma Skin Cancer in United States Blacks. Cancer Epidemiol Biomarkers Prev 2000; 9: 291-7.
Sharma MR, Werth B, Werth VP. Animal models of acute photodamage: comparisons of anatomic, cellular and molecular responses in C57BL/6J, SKH1 and Balb/c mice. Photochem Photobiol 2011; 87: 690-8. http://dx.doi.org/10.1111/j.1751-1097.2011.00911.x
Noonan FP, Hoffman HA. Susceptibility to immunosuppression by ultraviolet B radiation in the mouse. Immunogenetics 1994; 39: 29-39. http://dx.doi.org/10.1007/BF00171794
Golde WT, Gollobin P, Rodriguez LL. A rapid, simple, and humane method for submandibular bleeding of mice using a lancet. Lab Anim (NY) 2005; 34: 39-43. http://dx.doi.org/10.1038/laban1005-39
COUNCIL DIRECTIVE of 24 November 1986 on the approximation of laws, regulations and administrative provisions of the Member States regarding the protection of animals used for experimental and other scientific purposes (86/609/EEC) [Internet]. 1986;Available from: http://ec.europa.eu/food/fs/aw/aw_legislation/scientific/86-609-eec_en.pdf
Kripke ML. Antigenicity of murine skin tumors induced by ultraviolet light. J Natl Cancer Inst 1974; 53: 1333-6.
Fisher MS, Kripke ML. Systemic alteration induced in mice by ultraviolet light irradiation and its relationship to ultraviolet carcinogenesis. Proc Natl Acad Sci 1977; 74: 1688-92. http://dx.doi.org/10.1073/pnas.74.4.1688
Weill FS, Cela EM, Ferrari A, Paz ML, Leoni J, Gonzalez Maglio DH. Skin Exposure to Chronic But Not Acute UV Radiation Affects Peripheral T-Cell Function. J Toxicol Environ Health A 2011; 74): 838-47.
Weill FS, Cela EM, Paz ML, Ferrari A, Leoni J, González Maglio DH. Lipoteichoic acid from Lactobacillus rhamnosus GG as an oral photoprotective agent against UV-induced carcinogenesis. Br J Nutr 2013; 109: 457-66. http://dx.doi.org/10.1017/S0007114512001225
Wilgus TA, Ross MS, Parrett ML, Oberyszyn TM. Topical application of a selective cyclooxygenase inhibitor suppresses UVB mediated cutaneous inflammation . Prostaglandins Other Lipid Mediat 2000; 62: 367-84. http://dx.doi.org/10.1016/S0090-6980(00)00089-7
Hatton JL, Parent A, Tober KL, et al. Depletion of CD4+ cells exacerbates the cutaneous response to acute and chronic uvb exposure. J Invest Dermatol 2007; 127: 1507-15. http://dx.doi.org/10.1038/sj.jid.5700746
Fischer SM, Lo HH, Gordon GB, et al. Chemopreventive activity of celecoxib, a specific cyclooxygenase-2 inhibitor, and indomethacin against ultraviolet light-induced skin carcinogenesis. Mol Carcinog 1999; 25: 231-40. http://dx.doi.org/10.1002/(SICI)1098-2744(199908)25:4<231::AID-MC1>3.0.CO;2-F
Pentland a P, Schoggins JW, Scott GA, Khan KN, Han R. Reduction of UV-induced skin tumors in hairless mice by selective COX-2 inhibition. Carcinogenesis 1999; 20: 1939-44. http://dx.doi.org/10.1093/carcin/20.10.1939
Tober KL, Wilgus TA, Kusewitt DF, Thomas-ahner JM, Maruyama T, Oberyszyn TM. Importance of the EP1 Receptor in Cutaneous UVB-Induced Inflammation and Tumor Development. J Invest Dermatol 2006; 126: 205-11. http://dx.doi.org/10.1038/sj.jid.5700014
Budiyanto A, Ahmed NU, Wu A, et al. Protective effect of topically applied olive oil against photocarcinogenesis following UVB exposure of mice. Carcinogenesis 2000; 21: 2085-90. http://dx.doi.org/10.1093/carcin/21.11.2085
Garssen J, de Gruijl F, Mol D, de Klerk A, Roholl P, Van Loveren H. UVA Exposure Affects UVB and cis-Urocanic Acid-Induced Systemic Suppression of Immune Responses in Listeria monocytogenes-infected. Photochem Photobiol 2001; 73: 432-8. http://dx.doi.org/10.1562/0031-8655(2001)073<0432:UEAUAC>2.0.CO;2
Gorman S, Tan JW-Y, Thomas JA, et al. Primary defect in UVB-induced systemic immunomodulation does not relate to immature or functionally impaired APCs in regional lymph nodes. J Immunol 2005; 174: 6677-85.
Schwarz A, Maeda A, Wild MK, et al. Ultraviolet radiation-induced regulatory T cells not only inhibit the induction but can suppress the effector phase of contact hypersensitivity. J Immunol 2004; 172: 1036-43.
Ullrich SE, Kripke ML. Mechanisms in the suppression of tumor rejection produced in mice by repeated UV irradiation. J Immunol 1984; 133: 2786-90.
Zhang Q, Yao Y, Konger RL, et al. UVB radiation-mediated inhibition of contact hypersensitivity reactions is dependent on the platelet-activating factor system. J Invest Dermatol 2008; 128: 1780-7. http://dx.doi.org/10.1038/sj.jid.5701251
Wang L, Jameson SC, Hogquist K a. Epidermal Langerhans cells are not required for UV-induced immunosuppression. J Immunol 2009; 183: 5548-53. http://dx.doi.org/10.4049/jimmunol.0900235
Waris G, Ahsan H. Reactive oxygen species: role in the development of cancer and various chronic conditions. J Carcinog 2006; 5: 14. http://dx.doi.org/10.1186/1477-3163-5-14
Aggarwal BB, Shishodia S, Sandur SK, Pandey MK, Sethi G. Inflammation and cancer: how hot is the link? Biochem Pharmacol 2006; 72: 1605-21. http://dx.doi.org/10.1016/j.bcp.2006.06.029