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The vitamin A metabolism and expression of retinoid-binding proteins differ in HaCaT cells and normal human keratinocytes
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Dermatology and Venereology)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Dermatology and Venereology)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Dermatology and Venereology)
1999 (English)In: Archives of Dermatological Research, ISSN 0340-3696, E-ISSN 1432-069X, Vol. 291, no 6, 339-345 p.Article in journal (Refereed) Published
Abstract [en]

HaCaT keratinocytes differ from normal human epidermal keratinocytes (HEK) by constitutive expression of differentiation markers which are normally suppressed by vitamin A. In search of an explanation for this discrepancy we compared the vitamin A content, the expression of retinoid-binding proteins, and the vitamin A metabolism in the two cell types. The concentrations of retinol and 3,4-didehydroretinol in cultured HaCaT cells were less than one-fifth those in HEK, and the content of fatty acyl esters was even lower. Similarly, the concentrations of cellular retinol-binding protein and cellular retinoic acid-binding protein (CRBPI and CRABPII, respectively) were 10-30 times lower in HaCaT cells than in HEK corresponding to a reduced mRNA expression of these proteins. Unexpectedly, HaCaT cells expressed RARbeta in addition to RARalpha, RARgamma and RXRalpha, which are nuclear receptors normally found in HEK. Radioactive retinol added to the culture medium appeared only transiently in HaCaT cells, and pulse labeling confirmed a defective cellular retention of retinyl esters. After 24 h of incubation with [3H]retinol, cell-associated radioactivity corresponding to retinol, 3,4-didehydroretinol, all-trans-retinoic acid and 3,4-didehydroretinoic acid was found in both HaCaT cells and HEK. [3H]Retinoic acid showed a more rapid metabolism to 4-hydroxy/4-keto-retinoic acid in HaCaT cells than in HEK, which could be explained by a higher expression of cytochrome p450RAI in the former cells. In conclusion, the abnormal uptake of vitamin A and low levels of retinoid binding proteins in HaCaT cells, linked with an aberrant metabolism of retinol, may help to explain why these cells differentiate also in the presence of retinoids.

Place, publisher, year, edition, pages
1999. Vol. 291, no 6, 339-345 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-55901DOI: 10.1007/s004030050419PubMedID: 10421060OAI: oai:DiVA.org:uu-55901DiVA: diva2:83809
Available from: 2008-10-17 Created: 2008-10-17 Last updated: 2017-12-04Bibliographically approved

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