NHEK AND INCREASED HSPs 153 C'CI 50 E m .c 40 m 30 C C 20 0 ::I 10 � 0 o o 20 40 60 7- dehydrocholesterol (ug/cm2) Figure 3. Effects of 7-DHC pretreatment on the induction of skin color by UVB. Skin was pretreated two hours before UVB irradiation with 20, 40, and 60 µg/ml of 7-DHC per square cm of skin. shock proteins inducing 1,25-dihydroxyvitamin D3. This transformation would be ini tiated by UV light and may provide a feedback protective system against the denaturing and damaging effects of UV. The induction of heat shock proteins in human skin provides a protective effect against stresses such as heat and UVB exposure. The expres sion of heat shock proteins in the epidermis after solar simulation has been described by Brunet and Giacomoni (25) and after UVA irradiation by Trautinger et al. (26). It has also been found that it provides protection against UVB irradiation (27-29). This has been further supported by work in mice with mutated HSP70. These mice were found to be more sensitive to UVB irradiation and damage (30). In addition, keratinocytes injected with neutralizing antibody for HSP70 have increased sensitivity to UVB induced cell death (31). This suggests that HSP70 provides a protective mechanism against UVB as well as hypertherma. Non-toxic methods of inducing heat shock proteins would be of value in the develop ment of biologically active sun-protection products. The use of 7-dehydrocholesterol may provide this type of benefit when used in sun-protection products. REFERENCES (1) K. Nakamura, K. Rokutan, N. Marni, A. Aoike, and K. Kawai, Induction of heat shock proteins and their implication in protection against ethanol-induced damage in cultured guinea pig gastric mucosal cells, Gastroenterology, 101, 161-166 (1991). (2) Y. Liu, H. Kato, N. Nakata, and K. Kogure, Protection of rat hippocampus against ischemic neuronal damage by pretreatment with sublethal ischemia, Brain Res., 586, 121-124 (1992). (3) V. L. Gabai and A. E. Kabakov, Rise in heat-shock protein level confers tolerance to energy depriva tion, FEBS Lett., 327, 247-250 (1993). (4) R. S. Williams, J. A. Thomas, M. Fina, Z. German, and I. J. Benjamin, Human heat shock protein 70 (hsp70) protects murine cells from injury during metabolic stress,]. Clin. Invest., 92, 503-508 (1993).
154 JOURNAL OF COSMETIC SCIENCE (5) M. M. Hutter, R. E. Sievers, V. Barbosa, and C. L. Wolfe, Heat-shock protein induction in rat hearts: A direct correlation between the amount of heat-shock protein induced and the degree of myocardial protection, Circulation, 89, 355-360 (1994). (6) M. M. Simon, A. Reikerstorfer, A. Schwarz, C. Krone, T. A. Luger, M. Jaattela, and T. Schwarz, Heat shock protein 70 overexpression affects the response to ultraviolet light in murine fibroblasts: Evidence for increased cell viability and suppression of cytokine release,]. Clin. Invest., 95, 926-933 (1995). (7) M. T. Kiriyama, M. Oka, M. Takehana, and S. Kobayashi, Expression of a small heat shock protein 27 (HSP27) in mouse skin tumors induced by DVB-irradiation, Biol. Pharm. Bull., 24, 197-200 (2001). (8) S. I. Rattan, Repeated mild heat shock delays aging in cultured human skin fibroblasts, Biochem. Mol. Biol. Int., 45, 753-759 (1998). (9) G. C. Li, Induction of thermotolerance and enhanced heat shock protein synthesis in Chinese hamster fibroblasts by sodium arsenite and ethanol,]. Cell. Physiol., 115, 116-122 (1985). (10) G. C. Li and G. M. Hahn, Ethanol-induced tolerance to heat and to adriamycin, Nature, 274, 699-701 (1987). (11) G. C. Li and J. Y. Mak, Induction of heat shock protein synthesis in murine tumors during the development of thermotolerance, Cancer Res., 45, 3816-3824 (1985). (12) B. S. Palla, A. M. Healy, E. P. Amento, and S. M. Krane, 1,25-Dihydroxyvitamin D3 maintains adherence of human monocytes and protects them from thermal injury,]. Clin. Invest., 77, 1332-1339 (1986). (13) S. M. Krane, B. S. Palla, and J. V. Bonventre, 1,25-Dihydroxyvitamin D3 increases the toxicity of hydrogen peroxide: The role of calcium and heat shock, Exp. Gerontol., 25, 239-245 (1990). (14) S. Pillai, D. D. Bikle, and P. M. Elias, 1,25-Dihydroxyvitamin D production and receptor binding in human keratinocytes varies with differentiation,]. Biol. Chem., 263, 5390-5395 (1988). (15) K. Matsumoto, Y. Azuma, M. Kiyoki, H. Okumura, K. Hashimoto, and K. Yoshikawa, Involvement of endogenously produced 1,25-dihydroxyvitamin D-3 in the growth and differentiation of human keratinocytes, Biochim. Biophys. Acta, 1092, 311-318 (1991). (16) M. Sebag, W. Gulliver, and R. Kremer, Effect of 1,25 dihydroxyvitamin D3 and calcium on growth and differentiation and on c-fos and p53 gene expression in normal human keratinocytes,]. Invest. Dermatol., 103, 323-329 (1994). (1 7) Y. Kitano, N. Ikeda, and M. Okano, Suppression of proliferation of human epidermal keratinocytes by 1,25-dihydroxyvitamin D3. Analysis of its effect on psoriatic lesions and of its mechanism using human keratinocytes in culture, Eur.]. Clin. Invest., 21, 53-58 (1991). (18) 0. Garach-Jehoshua, A. Ravid, U. A. Liberman, and R. Koren, 1,25-Dihydroxyvitamin D3 increases the growth-promoting activity of autocrine epidermal growth factor receptor ligands in keratinocytes, Endocrinology, 140, 713-721 (1999). (19) W. B. Bollag, J. Ducote, and C. S. Harmon, Biphasic effect of 1,25-dihydroxyvitamin D3 on primary mouse epidermal keratinocyte proliferation,]. Cell. Physiol., 163, 248-256 (1995). (20) J. Lee and J. I. Youn, The photoprotective effect of 1,25-dihydroxyvitamin D3 on ultraviolet light B-induced damage in keratinocytes and its mechanism of action,]. Dermatol. Sci., 18, 11-18 (1998). (21) K. Hanada, D. Sawamura, H. Nakano, and I. Hashimoto, Possible role of 1,25-dihydroxyvitamin D3-induced metallothionein in photoprotection against UVB injury in mouse skin and cultured rat keratinocytes,j. Dermatol. Sci., 9, 203-208 (1995). (22) S. Ray, R. Ray, and M. F. Bolick, Metabolism of 3H-1 alpha, 25-dihydroxyvitamin D3 in cultured human keratinocytes,j. Cell. Biochem., 59, 117-122 (1995). (23) D. D. Bikle, M. K. Nemanic, E. Gee, and P. Elias, 1,25-Dihydroxyvitamin D3 production by human keratinocytes: Kinetics and regulation,]. Clin. Invest., 78, 557-566 (1986). (24) B. Lehmann, T. Genehr, P. Knuschke, J. Pietzsch, and M. Meurer, DVB-induced conversion of 7-dehydrocholesterol to 1 alpha, 25-dihydroxyvitamin D3 in an in vitro human skin equivalent model.,]. Invest. Dermatol., 117, 1179-1185 (2001). (25) S. Brunet and P. U. Giacomoni, Heat shock mRNA in mouse epidermis after UV irradiation, Mutat. Res., 219, 217-224 (1989). (26) F. Trautinger, I. Kindas-Mugge, R. M. Knobler, and H. Honigsmann, Stress proteins in the cellular response to ultraviolet radiation,]. Photochem. Photobiol. B, 35, 141-148 (1996). (27) E. V. Maytin, J. M. Wimberly, and K. S. Kane, Heat shock modulates DVB-induced cell death in human epidermal keratinocytes: Evidence for a hyperthermia-inducible protective response,]. Invest. Dermatol., 103, 547-553 (1994).
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