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Publication : An analysis of retinoic acid-induced gene expression and metabolism in AB1 embryonic stem cells.

First Author  Chen AC Year  1996
Journal  J Biol Chem Volume  271
Issue  25 Pages  14971-80
PubMed ID  8663043 Mgi Jnum  J:33702
Mgi Id  MGI:81179 Doi  10.1074/jbc.271.25.14971
Citation  Chen AC, et al. (1996) An analysis of retinoic acid-induced gene expression and metabolism in AB1 embryonic stem cells. J Biol Chem 271(25):14971-80
abstractText  Murine embryonic stem cells such as the AB1 cell line undergo differentiation in the presence of retinoic acid (RA) into an extraembryonic epithelial cell type. This results in the activation of genes such as Hoxa-1, Hoxb-1, laminin, collagen IV(alpha1), tissue plasminogen activator, RARbeta, and CRABPII. The CRABPI gene is regulated in an unusual fashion; CRABPI message and protein levels are induced at low concentrations of RA, but induction is diminished at higher concentrations. AB1 cells take up RA rapidly from the medium, and the addition of low, exogenous concentrations of RA to the culture medium results in very high intracellular RA concentrations. For example, AB1 stem cells cultured in 5 nM [3H]RA have an internal [3H]RA concentration of 1-2 microM within the first hour. AB1 cells also metabolize [3H]RA to more polar RA derivatives. The half-life of RA in AB1 cells not previously exposed to RA is about 2-2.5 h versus 40-45 min in cells cultured for 2-3 days in 1 microM exogenous RA. Thus, the enzyme(s) which metabolize RA are induced or activated by RA. Furthermore, the local concentration of RA required to elicit some biological responses may be higher than previously thought.
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