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J. Biol. Chem., Vol. 276, Issue 26, 24194-24202, June 29, 2001
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From the Multiple retinoic acid responsive cDNAs were
isolated from a high density cDNA microarray membrane, which was
developed from a cDNA library of human tracheobronchial epithelial
cells. Five selected cDNA clones encoded the sequence of the same
novel gene. The predicted open reading frame of the novel gene encoded
a protein of 319 amino acids. The deduced amino acid sequence contains
four motifs that are conserved in the short-chain alcohol
dehydrogenase/reductase (SDR) family of proteins. The novel gene shows
the greatest homology to a group of dehydrogenases that can oxidize
retinol (retinol dehydrogenases). The mRNA of the novel gene was
found in trachea, colon, tongue, and esophagus. In situ
hybridization of airway tissue sections demonstrated epithelial
cell-specific gene expression, especially in the ciliated cell type.
Both all-trans-retinoic acid and 9-cis-retinoic
acid were able to elevate the expression of the novel gene in primary
human tracheobronchial epithelial cells in vitro. This
elevation coincided with an enhanced retinol metabolism in these
cultures. COS cells transfected with an expression construct of the
novel gene were also elevated in the metabolism of retinol. The results
suggested that the novel gene represents a new member of the SDR family
that may play a critical role in retinol metabolism in airway epithelia
as well as in other epithelia of colon, tongue, and esophagus.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EMBL Data Bank with accession number(s) AY017349.
Characterization of a Novel Airway Epithelial
Cell-specific Short Chain Alcohol Dehydrogenase/Reductase Gene Whose
Expression Is Up-regulated by Retinoids and Is Involved in the
Metabolism of Retinol*
§¶,§
,,
Center for Comparative Respiratory Biology
and Medicine and the ** Department of Nutrition, University of
California at Davis, Davis, California 95616
*
This work was supported in part by Grants HL35635, ES06230,
ES09701, ES00628 from the National Institutes of Health (NIH).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Supported by American Lung Association Grant RG-025L N and NIH
F32 HL09573.
To whom all correspondence should be addressed: Center for
Comparative Respiratory Biology and Medicine, Surge 1 Bldg., Rm. 1121, University of California at Davis, One Shields Ave., Davis, CA 95616. Tel.: 530-752-2648; Fax: 530-752-8632; E-mail: rwu@ucdavis.edu.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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