Cellular retinoic acid-binding protein and its relationship to the biological activity of four synthetic retinoids in hamster tracheal organ culture |
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Authors: | Rajendra G Mehta Leonard J Schiff Steven J Moore Ann Marie Buckley Marcia I Dawson |
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Institution: | (1) Laboratory of Pathophysiology, Life Sciences Department, IIT Research Institute, 60616 Chicago, Illinois;(2) Bio-Organic Chemistry Laboratory, Life Sciences Division, SRI International, 94025 Menlo Park, California |
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Abstract: | Summary The mechanism of action of retinoid in reversing keratinization in hamster trachea is yet unknown. The purpose of this study
was to determine if cellular retinoic acid binding protein (CRABP) is present in tracheal epithelium following incubation
in serum-free, vitamin A-deficient culture medium for 10 days, and if the effectiveness of a retinoid in reversing keratinization
in organ culture is correlated with its ability to compete for CRABP sites. The cytosol prepared from tracheal cultures contained
CRABP at a concentration of 2.61 pmoles per mg protein. Of the four retinoids with carboxyl end group selected for the study,
two of the biological active retinoids competed for the CRABP sites. However, no correlation was observed between the biological
activity of the inactive retinoids and their ability to associate with the CRABP sites. These results indicate that even though
the action of retinoid may be mediated by retinoid binding protein, it cannot be used as a sole predicator of retinoid response
in hamster trachea.
This investigation was supported by Contract N01-CP-31012 and U. S. P. H. Grants CA30512 and CA32428, which were awarded by
the Division of Cancer Etiology, National Cancer Institute, DHHS.
Editor's Statement Tracheal organ cultures provide a useful model for the study of epithelial differentiation and carcinogenesis.
Much attention has been given to the action of retinoids in this process. Mehta et al. demonstrate a lack of correlation between
biological activity and specific cytosolic binding of members of this class of compounds, pointing out the need for a more
complete biochemical understanding of the mechanism of action and active forms of retinoids in this and other systems in vivo
and in vitro. David W. Barnes |
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Keywords: | cellular retinoic acid binding protein retinoids tracheal epithelium hamster trachea |
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