Novel function of metallothionein in photoprotection: metallothionein-null mouse exhibits reduced tolerance against ultraviolet B injury in the skin.
We have shown previously that injection of cadmium chloride (Cd2+) depletes the number of ultraviolet B (UVB)-induced sunburn cells in the mouse skin in vivo, and that Cd2+ treatment enhances UVB resistance in cultured keratinocytes in vitro, indicating the photoprotective role of Cd2+-induced metallothioneins (MT) with antioxidant property against UVB injury; however, there has been no direct evidence for the role of MT in UV protection. To improve our understanding of MT in photoprotection, MT-null mouse deficient in its MT-1 and MT-2 genes was studied. Skin explants were preliminarily exposed to medium alone, Cd2+ and Cd2+ plus buthionine S,R-sulfoximine, an inhibitor of glutathione synthesis. We then compared the number of UVB-induced sunburn cells and apoptotic cells 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 sunburn cells and apoptotic cells 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 MT in the skin.
Hanada
K
K
Department of Dermatology, Hirosaki University School of Medicine, Japan.
Sawamura
D
D
Tamai
K
K
Baba
T
T
Hashimoto
I
I
Muramatsu
T
T
Miura
N
N
Naganuma
A
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002104:Cadmium / Q000494:pharmacology; D020287:In Situ Nick-End Labeling; D008297:Male; D008668:Metallothionein / Q000502:physiology*; D051379:Mice; D012867:Skin / Q000166:cytology / Q000528:radiation effects*; D013471:Sunburn / Q000517:prevention & control; D013473:Sunscreening Agents / Q000494:pharmacology*; D014466:Ultraviolet Rays / Q000009:adverse effects*
D013473:Sunscreening Agents; D002104:Cadmium; D008668:Metallothionein