HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by YAMAMOTO, Y. Articles by ROSS, A. C. Search for Related Content PubMed PubMed Citation Articles by YAMAMOTO, Y. Articles by ROSS, A. C.

Regulation of CYP26 (cytochrome P450RAI) mRNA expression and retinoic acid metabolism by retinoids and dietary vitamin A in liver of mice and rats

Department of Nutrition and Department of Veterinary Science, The Pennsylvania State University, University Park, Pennsylvania 16802, USA

¹Correspondence: Department of Nutrition, 126-S Henderson Bldg., Pennsylvania State University, University Park, PA 16802, USA. E-mail: acr6{at}psu.edu

Retinoic acid (RA), through nuclear retinoid receptors, regulates the expression of numerous genes. However, little is known of the biochemical mechanisms that regulate RA concentration in vivo. CYP26 (P450RAI), a novel cytochrome P450, is expressed during embryonic development, induced by all-trans RA, and capable of catalyzing the oxidation of [³H]RA to polar retinoids including 4-oxo-RA. Here we report that CYP26 expression in adult liver is regulated by all-trans RA and dietary vitamin A, and is correlated with the metabolism of all-trans RA to polar metabolites. In normal mouse and rat liver, CYP26 mRNA was barely detectable; however, after acute treatment with all-trans RA CYP26 mRNA and RA metabolism by liver microsomes were significantly induced. Aqueous-soluble RA metabolites were detected, but their formation was not induced. The expression of retinoid receptors, RAR- and RXR-, was not changed after RA treatment in vivo. In a model of chronic vitamin A ingestion during aging, CYP26 mRNA expression, determined by Northern blot and RT-PCR analysis, increased progressively with dietary vitamin A (P<0.0001; marginal < control < supplemented) and age (P<0.003). The relative expression of CYP26 mRNA was positively correlated with liver total retinol (log₁₀), ranging from undetectable CYP26 expression at liver retinol concentrations below 20 nmol/g to a three- to fourfold elevation at concentrations >10,000 nmol/g (r=0.90, P<0.0001). We conclude that CYP26 expression and RA metabolism are regulated in adult liver not only acutely by RA administration, as may be relevant to retinoid therapy, but under chronic dietary conditions relevant to vitamin A nutrition in humans.—Yamamoto, Y., Zolfaghari, R., Ross, A. C. Regulation of CYP26 (cytochrome P450RAI) mRNA expression and retinoic acid metabolism by retinoids and dietary vitamin A in liver of mice and rats.

Key Words: retinoic acid oxidation • vitamin A status • aging

This article has been cited by other articles:

				R. Zolfaghari, C. J. Cifelli, S. O. Lieu, Q. Chen, N.-q. Li, and A. C. Ross Lipopolysaccharide opposes the induction of CYP26A1 and CYP26B1 gene expression by retinoic acid in the rat liver in vivo Am J Physiol Gastrointest Liver Physiol, April 1, 2007; 292(4): G1029 - G1036. [Abstract] [Full Text] [PDF]

				C. J. Cifelli and A. C. Ross Chronic Vitamin A Status and Acute Repletion with Retinyl Palmitate Are Determinants of the Distribution and Catabolism of all-trans-Retinoic Acid in Rats J. Nutr., January 1, 2007; 137(1): 63 - 70. [Abstract] [Full Text] [PDF]

				C. J. Cifelli and A. C. Ross All-trans-retinoic acid distribution and metabolism in vitamin A-marginal rats. Am J Physiol Gastrointest Liver Physiol, August 1, 2006; 291(2): G195 - G202. [Abstract] [Full Text] [PDF]

				L. Liu and L. J. Gudas Disruption of the Lecithin:Retinol Acyltransferase Gene Makes Mice More Susceptible to Vitamin A Deficiency J. Biol. Chem., December 2, 2005; 280(48): 40226 - 40234. [Abstract] [Full Text] [PDF]

				M. D. Gulkac, G. Akpinar, H. Ustun, and A. Ozon Kanli Effects of vitamin A on doxorubicin-induced chromosomal aberrations in bone marrow cells of rats Mutagenesis, May 1, 2004; 19(3): 231 - 236. [Abstract] [Full Text] [PDF]

				A. C. Ross and R. Zolfaghari Regulation of Hepatic Retinol Metabolism: Perspectives from Studies on Vitamin A Status J. Nutr., January 1, 2004; 134(1): 269S - 275. [Abstract] [Full Text] [PDF]

				A. C. Ross Retinoid Production and Catabolism: Role of Diet in Regulating Retinol Esterification and Retinoic Acid Oxidation J. Nutr., January 1, 2003; 133(1): 291S - 296. [Abstract] [Full Text] [PDF]

				R. Zolfaghari and A. C. Ross Lecithin:retinol acyltransferase from mouse and rat liver: cDNA cloning and liver-specific regulation by dietary vitamin A and retinoic acid J. Lipid Res., December 1, 2000; 41(12): 2024 - 2034. [Abstract] [Full Text]