| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 269, Issue 52, 32821-32827, 12, 1994
SB Kurlandsky, JH Xiao, EA Duell, JJ Voorhees and GJ Fisher
The biological activity of all-trans retinol, in human keratinocytes, was
investigated through metabolic and functional analyses that assessed the
capacity for retinol uptake and metabolism and the mechanism of
retinol-induced activation of gene transcription. Human keratinocytes
converted all-trans retinol predominantly to retinyl esters, which
accounted for 60 and 90% of cell-associated radiolabel after a 90-min pulse
and a 48-h chase, respectively. Human keratinocytes also metabolized
all-trans retinol to low levels of all- trans retinoic acid (11.47-131.3
ng/mg of protein) in a dose-dependent manner, between 0.3 and 10 microM
added retinol. Small amounts of 13- cis retinoic acid (5.47-8.62 ng/mg of
protein) were detected, but 9-cis retinoic acid was detected only when
keratinocytes were incubated with radiolabeled retinol. There was no
accumulation of the oxidized catabolic metabolites 4-hydroxy- or
4-oxoretinoic acid; however, 5,6- epoxy retinoic acid was detected at
pharmacological levels (10 and 30 microM) of added retinol. Biological
activity of retinol was assessed through analysis of two known retinoic
acid-mediated responses: 1) reduction of type I epidermal transglutaminase
and 2) activation of a retinoic acid receptor-dependent reporter gene, beta
RARE3-tk-CAT. Both all-trans retinol and all-trans retinoic acid reduced
type I epidermal transglutaminase in a dose-dependent manner; however, the
ED50 for all- trans retinol (10 nM) was 10 times greater than for all-trans
retinoic acid (1 nM). All-trans retinol also stimulated beta RARE3-tk-CAT
reporter gene activity in a dose-dependent manner. Half-maximal induction
was observed at 30 nM retinol, which was again 10-fold greater than
observed with all-trans retinoic acid. Cotransfection of human
keratinocytes with expression vectors for dominant negative mutant retinoic
acid and retinoid X receptors reduced retinol-induced beta RARE3-tk-CAT
reporter gene activation by 80%. Inhibition of conversion of all-trans
retinol or all-trans retinaldehyde to all-trans retinoic acid by citral
reduced beta RARE3-tk-CAT activity 98 and 86%, respectively. These data
demonstrate that retinol-induced responses in human keratinocytes are
mediated by its tightly regulated conversion to retinoic acid, which
functions as a ligand to activate nuclear retinoic acid receptors.
Biological activity of all-trans retinol requires metabolic conversion to all-trans retinoic acid and is mediated through activation of nuclear retinoid receptors in human keratinocytes
Department of Dermatology, University of Michigan, Ann Arbor 48109-0528.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  R. L. Sedjo, J. Ranger-Moore, J. Foote, N. E. Craft, D. S. Alberts, M.-J. Xu, and A. R. Giuliano Circulating Endogenous Retinoic Acid Concentrations among Participants Enrolled in a Randomized Placebo-Controlled Clinical Trial of Retinyl Palmitate Cancer Epidemiol. Biomarkers Prev., November 1, 2004; 13(11): 1687 - 1692. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. P. Simmons, F. Andreola, and L. M. De Luca Human melanomas of fibroblast and epithelial morphology differ widely in their ability to synthesize retinyl esters Carcinogenesis, November 1, 2002; 23(11): 1821 - 1830. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. J. Fisher, S. Kang, J. Varani, Z. Bata-Csorgo, Y. Wan, S. Datta, and J. J. Voorhees Mechanisms of Photoaging and Chronological Skin Aging Arch Dermatol, November 1, 2002; 138(11): 1462 - 1470. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Guo, A. Ruiz, R. R. Rando, D. Bok, and L. J. Gudas Esterification of all-trans-retinol in normal human epithelial cell strains and carcinoma lines from oral cavity, skin and breast: reduced expression of lecithin:retinol acyltransferase in carcinoma lines Carcinogenesis, November 1, 2000; 21(11): 1925 - 1933. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Lane, A. C. Chen, S. D. Roman, F. Derguini, and L. J. Gudas Removal of LIF (leukemia inhibitory factor) results in increased vitamin A (retinol) metabolism to 4-oxoretinol in embryonic stem cells PNAS, November 9, 1999; 96(23): 13524 - 13529. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. H. Gough, S. VanOoteghem, T. Sint, and N. Y. Kedishvili cDNA Cloning and Characterization of a New Human Microsomal NAD+-dependent Dehydrogenase that Oxidizes All-trans-retinol and 3alpha -Hydroxysteroids J. Biol. Chem., July 31, 1998; 273(31): 19778 - 19785. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. C. Roos, F. K. Jugert, H. F. Merk, and D. R. Bickers Retinoid Metabolism in the Skin Pharmacol. Rev., June 1, 1998; 50(2): 315 - 333. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. J. Fisher, Z. Wang, S. C. Datta, J. Varani, S. Kang, and J. J. Voorhees Pathophysiology of Premature Skin Aging Induced by Ultraviolet Light N. Engl. J. Med., November 13, 1997; 337(20): 1419 - 1429. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. B. Kurlandsky, E. A. Duell, S. Kang, J. J. Voorhees, and G. J. Fisher Auto-regulation of Retinoic Acid Biosynthesis through Regulation of Retinol Esterification in Human Keratinocytes J. Biol. Chem., June 28, 1996; 271(26): 15346 - 15352. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Soref, Y.-P. Di, L. Hayden, Y. H. Zhao, M. A. Satre, and R. Wu 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 J. Biol. Chem., June 22, 2001; 276(26): 24194 - 24202. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
