Photoprotection by 1,25 dihydroxyvitamin D3 is associated with an increase in p53 and a decrease in nitric oxide products.
Vitamin D is produced in skin by UVB radiation (290-320 nm) acting on 7-dehydrocholesterol. The hypotheses that the active vitamin D hormone, 1,25 dihydroxyvitamin D3 (1,25(OH)2D3), would increase the survival of skin cells after UV irradiation and that surviving cells after 1,25(OH)2D3 treatment would have no increase in DNA damage were tested. The survival of keratinocytes post-UVR was significantly greater after treatment with 1,25(OH)2D3 compared to vehicle (P<0.01). Significant reductions in thymine dimers (TDs) in surviving keratinocytes after UVR were noted in the presence of 1,25(OH)2D3 (P<0.001). Nuclear p53 protein expression increased after UVR and was significantly higher in keratinocytes treated with 1,25(OH)2D3 (P<0.01), whereas NO products were significantly reduced (P<0.05). Both the increase in nuclear accumulation of p53 protein and reduced formation of nitric oxide products may contribute to the reduction in TDs seen with 1,25(OH)2D3 after UVR. Reductions in numbers of sunburn cells (P<0.01) and in TDs (P<0.05) were observed 24 hours after UVR in skin sections from Skh:hr1 mice treated with 1,25(OH)2D3. These results are consistent with the proposal that the vitamin D system in skin may be part of an intrinsic protective mechanism against UV damage.
Gupta
Ritu
R
Department of Physiology and The Bosch Institute, University of Sydney, Sydney, New South Wales, Australia.
Dixon
Katie M
KM
Deo
Shivashni S
SS
Holliday
Carolyn J
CJ
Slater
Michael
M
Halliday
Gary M
GM
Reeve
Vivienne E
VE
Mason
Rebecca S
RS
D000818:Animals; D017209:Apoptosis; D002117:Calcitriol / Q000494:pharmacology*; D002467:Cell Nucleus / Q000378:metabolism; D004249:DNA Damage; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000528:radiation effects; D008027:Light; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D012867:Skin / Q000528:radiation effects; D013941:Thymine / Q000737:chemistry; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014466:Ultraviolet Rays; D014807:Vitamin D / Q000378:metabolism
D016159:Tumor Suppressor Protein p53; D014807:Vitamin D; D009569:Nitric Oxide; D002117:Calcitriol; D013941:Thymine