Differential expression of selenoproteins by human skin cells and protection by selenium from UVB-radiation-induced cell death.
The generation of reactive oxygen species has been implicated as part of the mechanism responsible for UVB-radiation-induced skin damage. In mice, evidence suggests that increased dietary selenium intake may protect skin from many of the harmful effects of UVB radiation. We sought to determine the selenoprotein profile of cultured human skin cells and whether selenium supplementation could protect keratinocytes and melanocytes from the lethal effects of UVB radiation. Labelling experiments using [75Se]selenite showed qualitative and quantitative differences in selenoprotein expression by human fibroblasts, keratinocytes and melanocytes. This was most noticeable for thioredoxin reductase (60 kDa) and phospholipid glutathione peroxidase (21 kDa); these proteins were identified by Western blotting. Despite these differences, we found that a 24 h preincubation with sodium selenite or selenomethionine protected both cultured human keratinocytes and melanocytes from UVB-induced cell death. With primary keratinocytes, the greatest reduction in cell death was found with 10 nM sodium selenite (79% cell death reduced to 21.7%; P<0.01) and with 50 nM selenomethionine (79% cell death reduced to 13.2%; P<0.01). Protection could be obtained with concentrations as low as 1 nM with sodium selenite and 10 nM with selenomethionine. When selenium was added after UVB radiation, little protection could be achieved, with cell death only being reduced from 88.5% to about 50% with both compounds. In all of the experiments sodium selenite was more potent than selenomethionine at providing protection from UVB radiation.
Rafferty
T S
TS
Department of Dermatology, University of Edinburgh, Lauriston Place, Edinburgh EH3 9YW, Scotland, UK. tr@srv1.med.ed.ac.uk
McKenzie
R C
RC
Hunter
J A
JA
Howie
A F
AF
Arthur
J R
JR
Nicol
F
F
Beckett
G J
GJ
D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000235:genetics*; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D011506:Proteins / Q000378:metabolism*; D012644:Selenium Radioisotopes / Q000378:metabolism; D012645:Selenomethionine / Q000494:pharmacology; D051140:Selenoproteins; D012867:Skin / Q000378:metabolism*; D018038:Sodium Selenite / Q000494:pharmacology; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects*
D011506:Proteins; D012644:Selenium Radioisotopes; D051140:Selenoproteins; D012645:Selenomethionine; D005979:Glutathione Peroxidase; D013880:Thioredoxin-Disulfide Reductase; D018038:Sodium Selenite