Effects of cadmium and zinc on solar-simulated light-irradiated cells: potential role of zinc-metallothionein in zinc-induced genoprotection.
Zinc is an essential oligoelement for cell growth and cell survival and has been demonstrated to protect cells from oxidative stress induced by UVA or from genotoxic stress due to UVB. In a recent work we demonstrated that the antioxidant role of zinc could be related to its ability to induce metallothioneins (MTs). In this study we identified the mechanism of zinc protection against solar-simulated light (SSL) injury. Cultured human keratinocytes (HaCaT) were used to examine MTs expression and localization in response to solar-simulated radiation. We found translocation to the nucleus, with overexpression of MTs in irradiated cells, a novel observation. The genoprotective effect of zinc was dependent on time and protein synthesis. DNA damage was significantly decreased after 48 h of ZnCl(2) (100 microM) treatment and is inhibited by actinomycin D. ZnCl(2) treatment (100 microM) led to an intense induction, redistribution, and accumulation of MT in the nucleus of irradiated cells. MT expression correlated with the time period of ZnCl(2) treatment. CdCl(2), a potent MT inducer, did not show any genoprotection, although the MTs were expressed in the nucleus. Overall our findings demonstrate that MTs could be a good candidate for explaining the genoprotection mediated by zinc on irradiated cells.
Jourdan
Eric
E
Laboratoire de Biologie du Stress Oxydant LBSO/LCR7 No. 8, Université Joseph Fourier, F-38043 Cedex 03, Grenoble, France.
Emonet-Piccardi
Nathalie
N
Didier
Christine
C
Beani
Jean-Claude
JC
Favier
Alain
A
Richard
Marie-Jeanne
MJ
D002104:Cadmium / Q000494:pharmacology*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D002478:Cells, Cultured; D002712:Chlorides / Q000494:pharmacology; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D008668:Metallothionein / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D011837:Radiation-Protective Agents / Q000494:pharmacology; D013472:Sunlight; D013997:Time Factors; D015032:Zinc / Q000494:pharmacology*; D017967:Zinc Compounds / Q000494:pharmacology
D002712:Chlorides; D011837:Radiation-Protective Agents; D017967:Zinc Compounds; C021267:zinc thionein; D002104:Cadmium; C016837:zinc chloride; D008668:Metallothionein; D015032:Zinc