Abstract
The skin is under the influence of oscillatory factors such as light and temperature. This organ possesses a local system that controls several aspects in a time-dependent manner; moreover, the skin has a well-known set of opsins whose function is still unknown. We demonstrate that heat shock reduces Opn2 expression in normal Melan-a melanocytes, while the opposite effect is found in malignant B16-F10 cells. In both cell lines, UVA. radiation increases the expression of Opn4 and melanin content. Clock genes and Xpa, a DNA. repair gene, of malignant melanocytes are more responsive to UVA. radiation when compared to normal cells. Most UVA-induced effects are antagonized by heat shock, a phenomenon shown for the first time. Based on our data, the heat produced during UV. experiments should be carefully monitored since temperature represents, according to our results, an important confounding factor, and therefore it should, when possible, be dissociated from UV. radiation. The responses displayed by murine melanoma cells, if proven to also take place in human melanoma, may represent an important step in cancer development and progression
Similar content being viewed by others
Abbreviations
- 6-4 PP:
-
6,4 Photoproducts
- Aqp3:
-
Aquaporin 3 gene
- BMAL1:
-
Aryl hydrocarbon receptor nuclear translocator- like protein 1
- Bmal1:
-
Aryl hydrocarbon receptor nuclear translocatorlike protein 1 gene
- CLOCK.:
-
Circadian locomotor output cycles kaput protein
- Clock:
-
Circadian locomotor output cycles kaput gene
- CPD:
-
Cyclobutane pyrimidine dimers
- CRY:
-
Cryptochrome protein
- Cry:
-
Cryptochrome gene
- DD:
-
Constant dark
- FBS:
-
Fetal bovine serum
- IPD:
-
Immediate pigment darkening
- LD:
-
Light-dark cycle
- PER:
-
Period protein
- Per:
-
Period gene
- PI:
-
Propidium iodide
- Rev-Erba/β:
-
RAR-related orphan receptor alpha/beta gene RORalβ Nuclear receptor subfamily 1, group D, member 1/2 gene
- SCNs:
-
Suprachiasmatic nuclei
- TPA:
-
Phorbol 12-myristate 13-acetate
- UVB:
-
Ultraviolet B radiation
- XPA:
-
Xeroderma pigmentosum, complementation group A protein
- Xpa:
-
Xeroderma pigmentosum, complementation group A. gene
- ZT:
-
Zeitgeber time
References
J. B. Hogenesch and H. R. Ueda, Understanding systems-level properties: timely stories from the study of clocks, Nat. Rev. Genet, 2011, 12, 407–416.
S. A. Brown and A. Azzi, Peripheral circadian oscillators in mammals, Handb. Exp. Pharmacol, 2013, 217, 45–66.
E. D. Buhr and J. S. Takahashi, Molecular components of the Mammalian circadian clock, Handb. Exp. Pharmacol, 2013, 217, 3–27.
J. A. Mohawk, C. B. Green and J. S. Takahashi, Central and peripheral circadian clocks in mammals, Annu. Rev. Neurosci., 2012, 35, 445–462.
M. R. Ralph, R. G. Foster, F. C. Davis and M. Menaker, Transplanted suprachiasmatic nucleus determines circadian period, Science, 1990, 247, 975–978.
S. Panda, I. Provencio, D. C. Tu, S. S. Pires, M. D. Rollag, A. M. Castrucci, M. T. Pletcher, T. K. Sato, T. Wiltshire, M. Andahazy, S. A. Kay, R. N. Van Gelder and J. B. Hogenesch, Melanopsin is required for non-image-forming photic responses in blind mice, Science, 2003, 301, 525–527.
I. Provencio, M. D. Rollag and A. M. Castrucci, Photoreceptive net in the mammalian retina. This mesh of cells may explain how some blind mice can still tell day from night, Nature, 2002, 415, 493.
D. M. Berson, F. A. Dunn and M. Takao, Phototransduction by retinal ganglion cells that set the circadian clock, Science, 2002, 295, 1070–1073.
S. Hughes, M. W. Hankins, R. G. Foster and S. N. Peirson, Melanopsin phototransduction: slowly emerging from the dark, Prog. Brain Res., 2012, 199, 19–40.
K. G. Baron and K. J. Reid, Circadian misalignment and health, Int. Rev. Psychiatry, 2014, 26, 139–154.
F. C. Kelleher, A. Rao and A. Maguire, Circadian molecular clocks and cancer, Cancer Lett., 2014, 342, 9–18.
C. Sawidis and M. Koutsilieris, Circadian rhythm disruption in cancer biology, Mol. Med., 2012, 18, 1249–1260.
S. Kawara, R. Mydlarski, A. J. Mamelak, I. Freed, B. Wang, H. Watanabe, G. Shiyji, S. K. Tavadia, H. Suzuki, G. A. Bjarnason, R. C. Jordan and D. N. Sauder, Low-dose ultraviolet B rays alter the mRNA. expression of the circadian clock genes in cultured human keratinocytes, J. Invest. Dermatol, 2002, 119, 1220–1223.
L. V. de Assis, M. N. Moraes, S. da Silveira Cruz-Machado and A. M. Castrucci, The effect of white light on normal and malignant murine melanocytes: A. link between opsins, clock genes, and melanogenesis, Biochim. Biophys. Acta, 2016, 1863, 1119–1133.
M. O. Poletini, L. V. M. de Assis, M. N. Moraes and A. M. L. Castrucci, Estradiol Differently Affects Melanin Synthesis of Malignant and Normal Melanocytes - a Relationship With Clock and Clock Controlled Genes, Mol. Cell. Biochem., 2016, 421, 29–39.
E. D. Buhr, S. H. Yoo and J. S. Takahashi, Temperature as a universal resetting cue for mammalian circadian oscillators, Science, 2010, 330, 379–385.
U. Abraham, A. E. Granada, P. O. Westermark, M. Heine, A. Kramer and H. Herzel, Coupling governs entrainment range of circadian clocks, Mol. Syst. Biol, 2010, 6, 438.
S. A. Brown, G. Zumbrunn, F. Fleury-Olela, N. Preitner and U. Schibler, Rhythms of mammalian body temperature can sustain peripheral circadian clocks, Curr. Biol, 2002, 12, 1574–1583.
C. Saini, J. Morf, M. Stratmann, P. Gos and U. Schibler, Simulated body temperature rhythms reveal the phase-shifting behavior and plasticity of mammalian circadian oscillators, Genes Dev., 2012, 26, 567–580.
F. Sporl, K. Schellenberg, T. Blatt, H. Wenck, K. P. Wittern, A. Schrader and A. Kramer, A. circadian clock in HaCa T. keratinocytes,J. Invest. Dermatol, 2011, 131, 338–348.
D. Gutierrez and J. Arbesman, Circadian Dysrhythmias, Physiological Aberrations, and the Link to Skin Cancer, Int. J. Mol. Sci., 2016, 17, 621.
A. J. Luber, S. H. Ensanyat and J. A. Zeichner, Therapeutic implications of the circadian clock on skin function, J. Drugs Dermatol, 2014, 13, 130–134.
M. S. Matsui, E. Pelle, K. Dong and N. Pernodet, Biological Rhythms in the Skin, Int. J. Mol. Sci., 2016, 17, 801.
M. V. Plikus, E. N. Van Spyk, K. Pham, M. Geyfman, V. Kumar, J. S. Takahashi and B. Andersen, The circadian clock in skin: implications for adult stem cells, tissue regeneration, cancer, aging, and immunity, J. Biol Rhythms, 2015, 30, 163–182.
C. Sandu, M. Dumas, A. Malan, D. Sambakhe, C. Marteau, C. Nizard, S. Schnebert, E. Perrier, E. Challet, P. Pevet and M. P. Felder-Schmittbuhl, Human skin keratinocytes, melanocytes, and fibroblasts contain distinct circadian clock machineries, Cell Mol Life Scl, 2012, 69, 3329–3339.
G. Yosipovitch, L. Sackett-Lundeen, A. Goon, C. Yiong Huak, C. Leok Goh and E. Haus, Circadian and ultradian (12 h) variations of skin blood flow and barrier function in non-irritated and irritated skin-effect of topical corticosteroids, J. Invest. Dermatol, 2004, 122, 824–829.
I. Le Fur, A. Reinberg, S. Lopez, F. Morizot, M. Mechkouri and E. Tschachler, Analysis of circadian and ultradian rhythms of skin surface properties of face and forearm of healthy women, J. Invest. Dermatol, 2001, 117, 718–724.
G. Yosipovitch, G. L. Xiong, E. Haus, L. Sackett-Lundeen, I. Ashkenazi and H. I. Maibach, Time-dependent variations of the skin barrier function in humans: transepidermal water loss, stratum corneum hydration, skin surface pH, and skin temperature, J. Invest. Dermatol, 1998, 110, 20–23.
N. Matsunaga, K. Itcho, K. Hamamura, E. Ikeda, H. Ikeyama, Y. Furuichi, M. Watanabe, S. Koyanagi and S. Ohdo, 24-hour rhythm of aquaporin-3 function in the epidermis is regulated by molecular clocks, J. Invest. Dermatol, 2014, 134, 1636–1644.
S. Gaddameedhi, C. P. Selby, W. K. Kaufmann, R. C. Smart and A. Sancar, Control of skin cancer by the circadian rhythm, Proc. Natl Acad. Sci. U. S. A, 2011, 108, 18790–18795.
M. Geyfman, V. Kumar, Q. Liu, R. Ruiz, W. Gordon, F. Espitia, E. Cam, S. E. Millar, P. Smyth, A. Ihler, J. S. Takahashi and B. Andersen, Brain and muscle Arntlike protein-1 (BMALl) controls circadian cell proliferation and susceptibility to UVB-induced DNA. damage in the epidermis, Proc. Natl Acad. Sci. U. S. A., 2012, 109, 11758–11763.
J. A. Hardman, D. J. Tobin, I. S. Haslam, N. Farjo, B. Farjo, Y. Al-Nuaimi, B. Grimaldi and R. Paus, The peripheral clock regulates human pigmentation, J. Invest. Dermatol, 2015, 135, 1053–1064.
M. Tanioka, H. Yamada, M. Doi, H. Bando, Y. Yamaguchi, C. Nishigori and H. Okamura, Molecular clocks in mouse skin, J. Invest. Dermatol, 2009, 129, 1225–1231.
B. Iyengar, The melanocyte photosensory system in the human skin, SpringerPlus, 2013, 2, 158.
G. J. Lopes, C. C. Gois, L. H. Lima and A. M. Castrucci, Modulation of rhodopsin gene expression and signaling mechanisms evoked by endothelins in goldfish and murine pigment cell lines, Braz.J. Med. Biol. Res., 2010, 43, 828–836.
Y. Miyashita, T. Moriya, T. Kubota, K. Yamada and K. Asami, Expression of opsin molecule in cultured murine melanocyte, J. Invest. Dermatol. Symp. Proc, 2001, 6, 54–57.
M. Tsutsumi, K. Ikeyama, S. Denda, J. Nakanishi, S. Fuziwara, H. Aoki and M. Denda, Expressions of rod and cone photoreceptor-like proteins in human epidermis, Exp. Dermatol, 2009, 18, 567–570.
K. Haltaufderhyde, R. N. Ozdeslik, N. L. Wicks, J. A. Najera and E. Oancea, Opsin expression in human epidermal skin, Photochem. Photobiol, 2015, 91, 117–123.
N. W. Bellono, L. G. Kammel, A. L. Zimmerman and E. Oancea, UV. light phototransduction activates transient receptor potential Al ion channels in human melanocytes, Proc. Natl Acad. Sci. U. S. A, 2013, 110, 2383–2388.
H. J. Kim, E. D. Son, J. Y. Jung, H. Choi, T. R. Lee and D. W. Shin, Violet light down-regulates the expression of specific differentiation markers through Rhodopsin in normal human epidermal keratinocytes, PLoS. One, 2013, 8, e73678.
N. L. Wicks, J. W. Chan, J. A. Najera, J. M. Ciriello and E. Oancea, UVA. phototransduction drives early melanin synthesis in human melanocytes, Curr. Biol, 2011, 21, 1906–1911.
E. Dupont, J. Gomez and D. Bilodeau, Beyond UV radiation: a skin under challenge, Int. J. Cosmet. Sci., 2013, 35, 224–232.
L. R. Sklar, F. Almutawa, H. W. Lim and I. Hamzavi, Effects of ultraviolet radiation, visible light, and infrared radiation on erythema and pigmentation: a review, Photochem. Photobiol Sci., 2013, 12, 54–64.
C. Fortes and E. de Vries, Nonsolar occupational risk factors for cutaneous melanoma, Int. J. Dermatol, 2008, 47, 319–328.
H. S. Lee, D. H. Lee, S. Cho and J. H. Chung, Minimal heating dose: a novel biological unit to measure infrared irradiation, Photo dermatol, Photoimmunol Photomed., 2006, 22, 148–152.
L. Calapre, E. S. Gray and M. Ziman, Heat stress: a risk factor for skin carcinogenesis, Cancer Lett, 2013, 337, 35–40.
J. S. Dover, T. J. Phillips and K. A. Arndt, Cutaneous effects and therapeutic uses of heat with emphasis on infrared radiation, J. Am. Acad. Dermatol, 1989, 20, 278–286.
L. H. Kligman, Intensification of ultraviolet-induced dermal damage by infrared radiation, Arch. Dermatol. Res., 1982, 272, 229–238.
L. H. Kligman and A. M. Kligman, Reflections on heat, Br. J. Dermatol, 1984, 110, 369–375.
D. C. Bennett, P. J. Cooper and I. R. Hart, A line of non-tumorigenic mouse melanocytes, syngeneic with the B16 melanoma and requiring a tumour promoter for growth, Int. J. Cancer, 1987, 39, 414–418.
C. Riccardi and I. Nicoletti, Analysis of apoptosis by propi-dium iodide staining and flow cytometry, Nat. Protoc, 2006, 1, 1458–1461.
K. J. Livak and T. D. Schmittgen, Analysis of relative gene expression data using real-time quantitative PCR. and the 2(-DeIta Delta C(T)) Method, Methods, 2001, 25, 402–408.
M. Kajstura, H. D. Halicka, J. Pryjma and Z. Darzynkiewicz, Discontinuous fragmentation of nuclear DNA. during apoptosis revealed by discrete “sub-G1” peaks on DNA. content histograms, Cytometry, Part A, 2007, 71, 125–131.
E. D. Buhr, W. W. Yue, X. Ren, Z. Jiang, H. W. Liao, X. Mei, S. Vemaraju, M. T. Nguyen, R. R. Reed, R. A. Lang, K. W. Yau and R. N. Van Gelder, Neuropsin (OPN5)-mediated photoentrainment of local circadian oscillators in mammalian retina and cornea, Proc. Natl Acad. Sci. U. S. A., 2015, 112, 13093–13098.
D. Kojima, S. Mori, M. Torii, A. Wada, R. Morishita and Y. Fukada, UV-sensitive photoreceptor protein OPN5 in humans and mice, PLoS. One, 2011, 6, e26388.
Y. J. Hwang, H. J. Park, H. J. Hahn, J. Y. Kim, J. H. Ko, Y. W. Lee, Y. B. Choe and K. J. Ahn, Immediate pigment darkening and persistent pigment darkening as means of measuring the ultraviolet A. protection factor in vivo: a comparative study, Br. J. Dermatol, 2011, 164, 1356–1361.
S. D. McAlear, T. W. Kraft and A. K. Gross, 1 rhodopsin mutations in congenital night blindness, Adv. Exp. Med. Biol, 2010, 664, 263–272.
M. C. Isoldi, M. D. Rollag, A. M. Castrucci and I. Provencio, Rhabdomeric phototransduction initiated by the vertebrate photopigment melanopsin, Proc. Natl Acad. Sci. U. S. A., 2005, 102, 1217–1221.
M. N. Moraes, L. H. Lima, B. C. Ramos, M. O. Poletini and A. M. Castrucci, Endothelin modulates the circadian expression of non-visual opsins, Gen. Comp. Endocrinol, 2014, 205, 279–286.
I. Provencio, G. Jiang, W. J. De Grip, W. P. Hayes and M. D. Rollag, Melanopsin: An opsin in melanophores, brain, and eye, Proc. Natl Acad. Sci. U. S. A., 1998, 95, 340–345.
G. Sikka, G. P. Hussmann, D. Pandey, S. Cao, D. Hori, J. T. Park, J. Steppan, J. H. Kim, V. Barodka, A. C. Myers, L. Santhanam, D. Nyhan, M. K. Halushka, R. C. Koehler, S. H. Snyder, L. A. Shimoda and D. E. Berkowitz, Melanopsin mediates light-dependent relaxation in blood vessels, Proc. Natl Acad. Sci. U. S. A., 2014, 111, 17977–17982.
H. Imai, V. Kefalov, K. Sakurai, O. Chisaka, Y. Ueda, A. Onishi, T. Morizumi, Y. Fu, K. Ichikawa, K. Nakatani, Y. Honda, J. Chen, K. W. Yau and Y. Shichida, Molecular properties of rhodopsin and rod function, J. Biol Chem., 2007, 282, 6677–6684.
M. Brenner and V. J. Hearing, The protective role of melanin against UV. damage in human skin, Photochem. Photobiol, 2008, 84, 539–549.
C. F. M. Menck and V. Munford, DNA. repair diseases: What do they tell us about cancer and aging?, Genet. Mol Biol, 2014, 37, 220–233.
S. Cho, M. H. Shin, Y. K. Kim, J. E. Seo, Y. M. Lee, C. H. Park and J. H. Chung, Effects of infrared radiation and heat on human skin aging in vivo, J. Invest. Dermatol Symp. Proc, 2009, 14, 15–19.
V. Cavallari, R. Cicciarello, V. Torre, M. E. Gagliardi, F. Albiero, R. Palazzo, M. Siragusa and C. Schipis, Chronic heat-induced skin lesions (erythema ab Igne): ultrastructural studies, Ultrastruct. Pathol, 2001, 25, 93–97.
L. Calapre, E. S. Gray, S. Kurdykowski, A. David, P. Hart, P. Descargues and M. Ziman, Heat-mediated reduction of apoptosis in UVB-damaged keratinocytes in vitro and in human skin ex vivo, BMC. Dermatol., 2016, 16, 6.
J. C. van der Leun, R. D. Piacentini and F. R. de GruijI, Climate change and human skin cancer, Photochem. Photobiol. Sci., 2008, 7, 730–733.
R. Jeronimo, M. N. Moraes, L. V. M. de Assis, B. C. Ramos, T. C. Rocha and A. M. L. Castrucci, Thermal Stress in Danio rerio: a Link between Temperature, Light, Thermo-TRP. Channels, and Clock Genes, J. Therm. Biol, 2016, Accepted manuscript.
N. Hamilton, N. Diaz-de-Cerio and D. Whitmore, Impaired light detection of the circadian clock in a zebrafish melanoma model, Cell Cycle, 2015, 14, 1232–1241.
Z. Lengyel, C. Lovig, S. Kommedal, R. Keszthelyi, G. Szekeres, Z. Battyani, V. Csernus and A. D. Nagy, Altered expression patterns of clock gene mRNAs and clock proteins in human skin tumors, Tumour Biol, 2013, 34, 811–819.
D. Hanahan and R. A. Weinberg, The hallmarks of cancer, Cell, 2000, 100, 57–70.
D. Hanahan and R. A. Weinberg, Hallmarks of cancer: the next generation, Cell, 2011, 144, 646–674.
T. H. Kang, L. A. Lindsey-Boltz, J. T. Reardon and A. Sancar, Circadian control of XPA. and excision repair of cisplatin-DNA. damage by cryptochrome and HERC2 ubiquitin ligase, Proc. Natl. Acad. Sci. U. S. A., 2010, 107, 4890–4895.
T. H. Kang, J. T. Reardon, M. Kemp and A. Sancar, Circadian oscillation of nucleotide excision repair in mammalian brain, Proc. Natl. Acad. Sci. U. S. A., 2009, 106, 2864–2870.
S. Gaddameedhi, C. P. Selby, M. G. Kemp, R. Ye and A. Sancar, The circadian clock controls sunburn apoptosis and erythema in mouse skin, J. Invest. Dermatol, 2015, 135, 1119–1127.
A. R. Muotri, M. C. N. Marchetto, M. F. Suzuki, K. Okazaki, C. F. P. Lotfi, G. Brumatti, G. P. Amarante-Mendes and C. F. M. Menck, Low amounts of the DNA. repair XPA. protein are sufficient to recover UV-resistance, Carcinogenesis, 2002, 23, 1039–1046.
A. Daponte, P. A. Ascierto, A. Gravina, M. Melucci, S. Scala, A. Ottaiano, E. Simeone, G. Palmieris and G. Cornelia, Temozolomide and cisplatin in avdanced malignant melanoma, Anticancer Res., 2005, 25, 1441–1447.
H. Helmbach, E. Rossmann, M. A. Kern and D. Schadendorf, Drug-resistance in human melanoma, Int. J. Cancer, 2001, 93, 617–622.
A. Slominski, D. J. Tobin, S. Shibahara and J. Wortsman, Melanin pigmentation in mammalian skin and its hormonal regulation, Physiol. Rev., 2004, 84, 1155–1228.
J. Y. Lin and D. E. Fisher, Melanocyte biology and skin pigmentation, Nature, 2007, 445, 843–850.
G. H. Findlay and L. W. Van der Merwe, The Meirowsky phenomenon. Colour changes in melanin according to temperature and redox potential, Br. J. Dermatol, 1966, 78, 572–576.
K. Maeda and M. Hatao, Involvement of photooxidation of melanogenic precursors in prolonged pigmentation induced by ultraviolet A. J. Invest. Dermatol, 2004, 122, 503–509.
K. Nakazawa, F. Sahuc, O. Damour, C. Collombel and H. Nakazawa, Regulatory effects of heat on normal human melanocyte growth and melanogenesis: comparative study with UVB, J. Invest. Dermatol, 1998, 110, 972–977.
T. B. Fitzpatrick and G. Szabo, Part III: General Considerations of Skin Pigmentation: The Melanocyte: Cytology and Cytochemistryl, J. Invest. Dermatol, 1959, 32, 197–206.
S. H. Kidson and B. C. Fabian, The effect of temperature on tyrosinase activity in Himalayan mouse skin, J. Exp. Zool, 1981, 215, 91–97.
F. G. Benedict, W. R. Miles and A. Johnson, The Temperature of the Human Skin, Proc. Natl Acad. Sci. U. S.A., 1919, 5, 218–222.
D. S. Kim, S. H. Park, S. B. Kwon, Y. H. Joo, S. W. Youn, U. D. Sohn and K. C. Park, Temperature regulates melanin synthesis in melanocytes, Arch. Pharmacol Res., 2003, 26, 840–845.
Author information
Authors and Affiliations
Additional information
Electronic supplementary information (ESI) available. See DOI: 10.1039/C6pp00330c
Rights and permissions
About this article
Cite this article
de Assis, L.V.M., Moraes, M.N. & de Lauro Castrucci, A.M. Heat shock antagonizes UVA-induced responses in murine melanocytes and melanoma cells: an unexpected interaction. Photochem Photobiol Sci 16, 633–648 (2017). https://doi.org/10.1039/c6pp00330c
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1039/c6pp00330c