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.
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.
Clinique de Dermatologie and DHURDV, Hôpital Universitaire, Genève, Switzerland.
D
D
Chatellard-Gruaz
R K
RK
Randolph
G
G
Hagens
J H
JH
Saurat
G
G
Siegenthaler
D001692:Biological Transport; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D006801:Humans; D007231:Infant, Newborn; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis / Q000235:genetics*; D012176:Retinoids / Q000378:metabolism*; D012867:Skin / Q000166:cytology*; D014212:Tretinoin / Q000031:analogs & derivatives / Q000378:metabolism*; D014316:Tritium; D014801:Vitamin A / Q000378:metabolism
D018168:Receptors, Retinoic Acid; D012176:Retinoids; C082928:retinoic acid binding protein II, cellular; D014316:Tritium; D014801:Vitamin A; D014212:Tretinoin