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J. Lipid Res.
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The Journal of Lipid Research, Vol. 39, 1421-1429, July 1998
Copyright © 1998 by Lipid Research, Inc.


Original Article

Differentiation of human epidermal keratinocytes is accompanied by increased expression of CRABP-II and increased cellular concentration of retinoic acids: retention of newly synthesized retinoic acids by CRABP-II

Dominique Chatellard-Gruaza, R. Keith Randolphb, Gerry Hagensa, Jean-Hilaire Saurata, and Georges Siegenthalera
a Clinique de Dermatologie and DHURDV, Hôpital Universitaire, CH-1211 Genève 14, Switzerland
b Living Skin Bank, University Hospital, SUNY at Stony Brook, Stony Brook, NY 11794

Correspondence to: Georges Siegenthaler.

Keratinocytes differentiating in vitro exhibit greater cytosolic capacity for retinoic acid synthesis from retinol or retinaldehyde as compared to nondifferentiated cells (Siegenthaler et al. 1990. Biochem. J. 268: 371–378), and increased expression of CRABP-II (Siegenthaler et al. 1988. Exp. Cell Res. 178: 114–126). Based on these observations, the content and disposition of [3H]retinoic acids were determined in intact, nondifferentiated and differentiating keratinocytes incubated with [3H]retinaldehyde or [3H]retinol. Differentiating keratinocytes contained higher levels of [3H] retinoic acids compared to undifferentiated cells when either [3H]retinaldehyde or [3H]retinol was the substrate. The largest increases in [3H]retinoic acids were achieved with [3H]retinaldehyde. Differentiation-associated increases in [3H]retinoic acids correlated with cellular content of retinoid alcohol substrates in incubations with retinaldehyde but not in incubations with retinol. Consistent with previous observations, CRABP-II was significantly increased in differentiating cells. Moreover, newly synthesized [3H]retinoic acids were retained within cells bound to CRABP-II.

The results suggest that increasing cellular concentration of retinoic acids in in vitro differentiating keratinocytes is achieved by a combination of increased activity of the retinoic acid synthesis pathway and increased cellular content of CRABP-II.—Chatellard-Gruaz, D., R. K. Randolph, G. Hagens, J-H. Saurat, and G. Siegenthaler. Differentiation of human epidermal keratinocytes is accompanied by increased expression of CRABP-II and increased cellular concentration of retinoic acids: retention of newly synthesized retinoic acids by CRABP-II. J. Lipid Res. 1998. 39: 1421–1429.

Supplementary key words: retinoic acid, 3,4-didehydroretinoic acid, retinol, retinaldehyde, retinoid, retinol esters, retinol esterification, cellular retinoic acid-binding protein


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