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The photoprotective effect of 1,25-dihydroxyvitamin D3 on ultraviolet light B-induced damage in keratinocyte and its mechanism of action

  • Joo-heung Lee
    Correspondence
    Corresponding author. Tel.: +82 32 8902230; fax: +82 32 8902238.
    Affiliations
    Department of Dermatology, Inha University Medical School/Hospital, 7-206, 3-ga, Shinheung-dong, Chung-gu, Incheon, South Korea
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  • Jai Il Youn
    Affiliations
    Department of Dermatology, College of Medicine, Seoul National University, 28, Yeonkun-dong, Chongro-gu, Seoul, South Korea
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      Abstract

      We investigated the photoprotective effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) both in vivo and in vitro, revealing its relationship with glutathione, a well-known antioxidant. We also probed into the possible mechanism of photoprotection of 1,25(OH)2D3 through immunohistochemical study for metallothionein (MT). At the same time, endogenous antioxidant effect of 1,25(OH)2D3 was examined. Survival of cultured human keratinocytes was decreased when the cells were irradiated with ultraviolet light-B (UVB) at doses above 30 mJ/cm2. But in the presence of 1,25(OH)2D3 (12 nM), the decrease of survival of keratinocytes by UVB was diminished. The formation of sunburn cells by UVB irradiation in the skin of ICR mice was inhibited by topical application of 1,25(OH)2D3, regardless of prior glutathione depletion. Immunohistochemical staining revealed that 1,25(OH)2D3 induced the expression of MT, a potent radical scavenger, mainly in the basal layer of ICR mice skin. 1,25(OH)2D3 neither inhibited peroxidation of plasma lipids nor interacted with superoxide, nor removed hydrogen peroxide as an antioxidant. These findings suggest that 1,25(OH)2D3 has photoprotective effect not related with glutathione or its endogenous antioxidant property. Rather, it could be attributed to 1,25(OH)2D3-induced MT and its capacity to prevent radical-related damage in UVB irradiation.

      Keywords

      Abbreviations:

      BSO, DL-buthionine-[S,R]-sulfoximine (), MT, metallothionein (), MTT test, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrasoliumbromide colorimetric assay (), SBC, sunburn cell (), UVB, ultraviolet light B (), 1,25(OH)2D3, 1,25-dihydroxyvitamin D3 ()
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      References

        • Binderup L.
        • Bramm E.
        Effects of a novel Vitamin D analogue MC903 on cell proliferation in vitro and on calcium metabolism in vivo.
        Biochem Pharmacol. 1988; 37: 889-895
      1. Collins ED, Norman AW. Vitamin D. In: Machlin LJ, editor. Handbook of Vitamins, 2nd ed. New York: Marcel Dekker, 1991:59–98.

        • Hosomi J.
        • Hosoi J.
        • Abe E.
        • Suda T.
        Regulation of terminal differentiation of cultured mouse epidermal cells by 1α,25-dihydroxyvitamin D3.
        Endocrinology. 1983; 113: 1950-1957
        • Hanada K.
        • Sawamura D.
        • Nakano H.
        • Hashimoto I.
        Possible role of calcitriol induced metallothionein in photoprotection against UVB injury in mouse skin and cultured rat keratinocytes.
        J Dermatol Sci. 1995; 9: 203-208
      2. Bremner I. Nutritional and physiological significance of metallothionein. In: Riordan JF, Vallee BL, editors. Methods in Enzymology; Metallochemistry, Part B, Metallothionein and Related Molecules, vol. 205. San Diego: Academic Press, 1991:25–35.

        • Koizumi S.
        • Sone T.
        • Otaki N.
        • Kimura M.
        Cd2+ induced synthesis of metallothionein in HeLa cells.
        Biochem J. 1985; 227: 879-886
        • Lieberman M.W.
        • Beach L.R.
        • Palmiter R.D.
        Ultraviolet radiation induced metallothionein-I gene activation is associated with extensive DNA demethylation.
        Cell. 1983; 35: 207-214
        • Durnam D.M.
        • Hoffman J.S.
        • Quaife C.J.
        • Benditt E.P.
        • Chen H.Y.
        • Brinster R.L.
        • Palmiter R.D.
        Induction of mouse metallothionein-1 mRNA by bacterial endotoxin is independent of metals and glucocorticoid hormones.
        Proc Natl Acad Sci USA. 1984; 81: 1053-1056
        • Karin M.
        Metallothioneins. Proteins in search of function.
        Cell. 1985; 41: 9-10
        • Thornalley P.J.
        • Vasak M.
        Possible role of metallothionein in protection against radiation induced oxidative stress. Kinetics and mechanism of its reaction with superoxide and hyroxyl radicals.
        Biochim Biophys Acta. 1985; 827: 36-44
        • Hanada K.
        • Gange R.W.
        • Siebert E.
        • Hasan T.
        Protective effects of cadmium chloride against UVB injury in mouse skin and in cultured human cells; a possible role of cadmium-induced metallothionein.
        Photodermatol Photoimmunol Photomed. 1991; 8: 111-115
        • Boyce S.T.
        • Ham R.G.
        Calcium regulated differentiation of normal human epidermal keratinocytes in chemically defined clonal cultures.
        J Invest Dermatol. 1983; 81: 33s-40s
        • Mosmann T.
        Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxic assays.
        J Immunol Methods. 1983; 65: 55
        • Ohkawa H.
        • Ohishi N.
        • Yagi K.
        Assay for lipid-peroxides in animal tissues by thiobarbituric acid reaction.
        Anal Biochem. 1979; 95: 351-358
        • Misra H.P.
        • Fridovich I.
        The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase.
        J Biol Chem. 1972; 247: 3170-3175
      3. Claiborne A. Catalase activity. In: Greenwald RA, editor. CRC Handbook of Methods for Oxygen Radical Research. Florida: CRC Press, 1986:283–284.

      4. Young AR. Chronic effects of ultraviolet radiation on the skin. In: Fitzpatrick TB, Eisen AZ, Wolff K, Freedberg IM, Austen KF, editor. Dermatology in General Medicine, 4th ed. New York: McGraw-Hill, 1993:1658–1660.

      5. Youn JI. Photoprotection in Photomedicine. Seoul: Yeomoongak, 1994:357–370.

        • Stocchi V.
        • Biagiarell B.
        • Fiorani M.
        • Palma F.
        • Piccoli G.
        • Cucchiarini L.
        • Dacha M.
        Inactivation of rabbit red blood cell hexokinase activity promoted in vitro by an oxygen radical generating system.
        Arch Biochem Biophys. 1994; 311: 160-167
      6. Jackson SM, Elias PM. Skin as an organ of protection. In: Fitzpatrick TB, Eisen AZ, Wolff K, Freedberg IM, Austen KF, editors. Dermatology in General Medicine, 4th ed. New York: McGraw-Hill, 1993:241–253.

        • Karasawa M.
        • Hosoi J.
        • Hashiba H.
        • Nose K.
        • Tohyama C.
        • Abe E.
        • Suda T.
        • Kuroki T.
        Regulation of metallothionein gene expression by a 1α,25-dihydroxyvitamin D3 in cultured cells and in mice.
        Proc Natl Acad Sci USA. 1987; 84: 8810-8813
        • Danno K.
        • Horio T.
        • Takigawa M.
        • Imamura S.
        Role of oxygen intermediates in UV-induced epidermal cell injury.
        J Invest Dermatol. 1984; 83: 166-168
        • Youn J.I.
        • Gange R.W.
        • Maytum D.
        • Parrish J.A.L.
        Effect of hypoxia on sunburn cell formation and inflammation induced by ultraviolet radiation.
        Photodermatology. 1988; 5: 252-256
        • Chubatsu L.S.
        • Gennari M.
        • Meneghini R.
        Glutathione is the antioxidant responsible for resistance to oxidative stress in V79 chinese hamster fibroblasts rendered resistant to cadmium.
        Chem Biol Interact. 1992; 82: 99-110
        • Youn J.I.
        • Park B.S.
        • Chung J.H.
        • Lee J.H.
        Photoprotective effect of vitamin D3 upon skin photoreaction to UVA and UVB.
        Photodermatol Photoimmunol Photomed. 1997; 13: 109-114