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Ultraviolet irradiation depletes cellular retinol and alters the metabolism of retinoic acid in cultured human keratinocytes and melanocytes
Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
Department of Medical Sciences, Sect. of Dermatol. and Venereology, Uppsala University, Uppsala, Sweden.
Department of Medical Sciences, Sect. of Dermatol. and Venereology, Uppsala University, Uppsala, Sweden.
1999 (English)In: Melanoma research, ISSN 0960-8931, E-ISSN 1473-5636, Vol. 9, no 4, 339-346 p.Article in journal (Refereed) Published
Abstract [en]

Vitamin A is an intrinsic modulator of proliferation and differentiation in human epidermis, and may be destroyed by ultraviolet radiation (UVR) impinging on the skin. To identify the deleterious effects of a perturbed cellular vitamin A status, we investigated the endogenous retinoid concentrations and the metabolism of [3H]retinol and all-trans [3H]retinoic acid in cultured human keratinocytes and melanocytes exposed to UVR, using high performance liquid chromatography. Before UVR the retinoid content was similar in keratinocytes and melanocytes, but the uptake of [3H]retinol was three-fold higher and the uptake of [3H]retinoic acid was 10-fold higher in the melanocytes. In both cell types, UVR (UVA 360 mJ/cm2 plus UVB 140 mJ/cm2) instantaneously reduced the concentration of retinol by about 50% and that of 3,4-didehydroretinol by about 20%. The retinoid concentrations returned to normal within 1-2 days post-irradiation, despite there being no overt increase in the uptake of [3H]retinol or the biosynthesis of 3,4- didehydroretinol. However, in both types of irradiated cells, the accumulation of the biologically most active metabolite, all-trans [3H]retinoic acid, was about 60% higher than in control cells. Furthermore, the metabolism of authentically supplied [3H]retinoic acid was reduced, especially in irradiated keratinocytes, which probably contributed to the restoration of retinoid levels after UV exposure.

Place, publisher, year, edition, pages
1999. Vol. 9, no 4, 339-346 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-24867PubMedID: 10504051Local ID: 9269OAI: oai:DiVA.org:liu-24867DiVA: diva2:245190
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2012-09-14Bibliographically approved
In thesis
1. Vitamin A and ß-carotene metabolism and effects of UV irradiation in human keratinocytes and melanocytes
Open this publication in new window or tab >>Vitamin A and ß-carotene metabolism and effects of UV irradiation in human keratinocytes and melanocytes
2002 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Retinoids (vitamin A and its derivatives) are modulators of proliferation and differentiation. Both retinol (ROH) and its metabolite 3,4-didehydroretinol (ddROH) can be converted to retinoic acid (RA) and 3,4-didehydroretinoic acid (ddRA), ligands for the nuclear receptors, which induce gene transcriptions. A perturbed ROH metabolism is observed in several dermatoses and iu non-melanoma skin cancer. Dietary ß-carotene has been considered to play a critical role in the natural defence against cancer. Whether ß-carotene is converted to ROH in the skin has been debated.

We have investigated ß-carotene and retinoid metabolism, retinoid binding proteins and retinoid receptors in human keratinocytes (KCs) and melanocytes (MCs) in vitro. Similar studies of vitamin A have been done in human malignant epithelial cells (HeLa) and malignant melanoma cells. The influence of ultraviolet radiation (UVR) on retinoid metabolism and receptor expression was specially focused upon this thesis. KCs and MCs contained high concentrations of ROH, ddROH, while HeLa- and melanoma cells contained lower levels. KCs contained the highest level of the retinoid-binding proteins CRBP I and CRABP II compared to MCs, HeLa and melanoma cells. High CRABP II levels showed a correlation with the ability to accumulate ddROH. In MCs, CRABP I was highly expressed, but in melanoma cells CRABP II dominated. The difference between MCs and melanoma cells in receptor levels was most pronounced for RARß, which was highly expressed in melanoma cells. Such dissimilarities between benign and malignant MCs might play a role in differentiation and growth regulation. The uptake of [3H]ROH, [3H]RA and ß-carotene was significantly higher in MCs than in KCs. We were able to demonstrate that [14C]ß-carotene was converted to [14C]ROH in both these cell types. This suggests that this local storage of ß-carotene might serve as au alternative supply for vitamin A in the skin.

A moderate dose of UVR reduced the concentration of ROH, ddROH and [3H]RA in KCs and MCs by 20-50%. The concentration returned to starting levels in 1-2 days, and could be explained by a retarded metabolism of RA, the biologically most active metabolite. When KCs and MCs were exposed to UVR, the mRNA and protein levels of the three nuclear retinoid receptors (RARα, RARγ and RXRα) decreased rapidly. In MCs these levels were close to normal 3 days postirradiation. In KCs only the RARα mRNA and protein levels returned to baseline within 3 days. This thesis has increased our knowledge of the effects of UVR on retinoid metabolism and retinoid receptors in human cells. Further studies are needed to understand the role of ß-carotene and retinoid signaling in UV induced skin cancer.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet, 2002. 66 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 725
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25546 (URN)9993 (Local ID)91-7373-169-2 (ISBN)9993 (Archive number)9993 (OAI)
Public defence
2002-07-01, Berzeliussalen, Universitetssjukhuset, Linköping, 13:00 (Swedish)
Opponent
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2012-09-14Bibliographically approved

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