Photoprotective role of metallothionein in UV-injury - metallothionein-null mouse exhibits reduced tolerance against ultraviolet-B.

We have shown previously that injection of cadmium chloride (Cd(2+)) depletes the number of ultraviolet B (UVB)-induced sunburn cells (SBC) in the mouse skin in vivo and that Cd(2+) treatment enhances UVB resistance in cultured keratinocytes in vitro, indicating the photoprotective role of Cd(2+)-induced metallothioneins (MTs) with antioxidant property against UVB injury. However, there has been no direct evidence for the role of MTs in UV protection. To improve our understanding of MTs in photoprotection, MT-null mouse deficient in MT-1 and MT-2 genes was studied. Skin explants were preliminarily exposed to medium alone, Cd(2+) and Cd(2+) plus buthionine S, R-sulfoximine (BSO), an inhibitor of glutathione synthesis. We then compared the number of UVB-induced SBC and apoptotic cells (AC) in the epidermis of MT-null mice with that of control mice using organ culture systems. The skin of MT-null mice developed a greater number of SBC and AC than did that of normal mice in all experimental conditions. These findings indicate that the skin of MT-null mouse is readily injured by UVB irradiation. MT-null mouse provided direct evidence of the photoprotective effect of cellular MTs in the skin.