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- Andersson, Eva, et al.
(författare)
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Differential effects of UV irradiation on the nuclear retinoid receptor levels of cultured keratinocytes and melanocytes
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Skin cancer is the most common malignancy in man. A major risk factor is UV irradiation, which not only damages DNA but may also perturb cellular signaling, e.g. via the retinoid receptor system believed to be important for cancer protection. We used cultured normal human keratinocytes and melanocytes to study the effects of UV radiation on the expression of the retinoid receptors RARα, RARβ, RARγ and RXRα. By real-time PCR and Western blot technique, the mRNA and protein levels were monitored, before and up to 4 days following 50 mJ/cm2 UVB. In keratinocytes, UVB caused a rapid drop in all four mRNA levels (minus 50-70% the first 8 h) and protein levels dropped by 30-40% followed by a gradual increase, but full normalization was ouly reached for RARα within the study period. ln melanocytes, UVB caused a quick drop both in the receptor mRNA and protein levels (minus 50-60% after 4 h), followed by normalization of the protein levels for all receptors within 2-3 days. The UV-induced depletion of vitamin A and retinoid receptors might abrogate the retinoid signaling, which subsequently might promote tumor development.
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| 2. |
- Andersson, Eva, et al.
(författare)
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The metabolism of vitamin A to 3,4-didehydroretinol can be demonstrated in human keratinocytes, melanoma cells and HeLa cells, and is correlated to cellular retinoid-binding protein expression
- 1994
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Ingår i: Biochimica et Biophysica Acta. Molecular Cell Research. - : Elsevier BV. - 0167-4889 .- 1879-2596. ; 1224:3, s. 349-354
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Tidskriftsartikel (refereegranskat)abstract
- Conversion of retinol to 3,4-didehydroretinol is probably a rate-limiting step in the formation of 3,4-didehydroretinoic acid, a candidate ligand for nuclear retinoid receptors in human epidermal keratinocytes. To investigate whether this metabolic pathway also exists in other cell systems, we compared the retinoid concentrations and the bioconversion of [3H]retinol to [3H]3,4-didehydroretinol in human primary keratinocytes, human cervical carcinoma (HeLa) cells, human melanoma (JKM86-4) cells, monkey kidney epithelium (CV-1) cells, and murine teratocarcinoma (F9) cells. The cellular retinol concentration ranged from 2.33 to 99.1 pmol/mg protein with the highest values observed in keratinocytes. 3,4-Didehydroretinol was only detected in cells of human origin and its concentration ranged from 0.24 pmol/mg in HeLa to 34.6 pmol/mg in the keratinocytes. Incubation with [3H]retinol for 1–24 h resulted in a rapid appearance of [3H]3,4-didehydroretinol in human keratinocytes, and to a lesser extent in HeLa and melanoma cells, but not in the other cells. Analysis of cellular retinol- and retinoic acid-binding protein concentrations showed a correlation to the cells' ability to accumulate 3,4-didehydroretinol, suggesting a role for these proteins in the 3,4-didehydro metabolic pathway. The combined results suggest that although 3,4-didehydroretinol is most typical for human keratinocytes, studies of its metabolism are also feasible in HeLa cells which contain low levels of retinoid-binding proteins.
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