Cloning of rat cytochrome P450RAI (CYP26) cDNA and regulation of its gene expression by all-trans-retinoic acid in vivo

Wang, Yuanping; Zolfaghari, Reza; Ross, A. Catharine

doi:10.1016/s0003-9861(02)00043-7

Cited by 76 publications

(82 citation statements)

References 37 publications

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“…22 This result is consistent with that obtained in the present study; an increase in the elimination (clearance) of ATRA after 180 minutes of IV administration. Results obtained in rats in the present study seem similar to those recorded in monkeys subjected to IV injection of ATRA, 20 involving plasma disappearance of ATRA characterized by 3 distinct phases: a brief, initial exponential decline followed by a relative plateau in the disappearance curve (the duration of which was dose dependent), and finally, a terminal exponential decay.…”

Section: Discussionsupporting

confidence: 93%

Pharmacokinetics of the time-dependent elimination of all-trans-retinoic acid in rats

Saadeddin

Torres‐Molina

Carcel-Trullols

et al. 2004

AAPS J

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KEYWORDS: all-trans-retinoic acid, time-dependent elimination, pharmacokinetic model, rat, intravenous administration, oral administration The time-dependent elimination kinetics of all-transretinoic acid (ATRA) has been associated with autoinduction of its metabolism and has led to the hypothesis that rapid development of acquired clinical resistance to ATRA may be prevented by coadministration of metabolic inhibitors. This study in rats was performed to investigate the pharmacokinetics and onset of timedependent elimination of ATRA, with the purpose of establishing an animal model suitable for in vivo preclinical studies of compounds capable of inhibiting ATRA metabolism. After the intravenous (IV) bolus administration of single doses of ATRA (1.60 mg kg ), the plasma concentration-time curves showed an accelerated decline at 180 minutes after dosing. The plasma clearance (Cl) of ATRA, determined after IV administration of a second dose (1.60 mg kg -1 ), at 180 minutes was greater than Cl after a single dose, thus indicating the existence of a time-dependent elimination process detectable 180 minutes after administration of the first dose. Such time-dependent elimination was confirmed by means of an IV constant-rate infusion of 0.48 mg h -1 kg -1 of ATRA during 10 hours. Peak plasma ATRA concentration was achieved at 180 minutes, after which the plasma concentration decreased to reach a much lower apparent steady-state drug concentration at 420 minutes. The area under the plasma concentration-time curve (AUC) obtained after oral administration of a second ATRA dose (1.60 mg kg -1 ) was ~8% of the AUC obtained after a single oral dose; consistent with a time-dependent increase in the elimination of ATRA, as was observed after IV administration.

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Section: Discussionsupporting

confidence: 93%

Pharmacokinetics of the time-dependent elimination of all-trans-retinoic acid in rats

Saadeddin

Torres‐Molina

Carcel-Trullols

et al. 2004

AAPS J

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“…In vitamin A-deficient rats, the testicular expression of Cyp26a1 becomes undetectable (Wang et al, 2002), possibly reflecting the presence of a canonical RA response element in the Cyp26a1 promoter region (Loudig et al, 2005). However, expression of the RA-degrading enzymes Cyp26a1 and Cyp26b1 is apparently not decreased in the peritubular cells of vitamin A-deficient mice (present study).…”

Section: Vitamin A-deficiency Affects Ra Synthesis But Not Ra Degradamentioning

confidence: 44%

Retinoids and spermatogenesis: Lessons from mutant mice lacking the plasma retinol binding protein

et al. 2006

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Using Rbp4-null mice as models, we have established for the first time the kinetics of the spermatogenetic alterations during vitamin A deficiency (VAD). Our data demonstrate that the VAD-induced testicular degeneration arises through the normal maturation of germ cells in a context of spermatogonia differentiation arrest. They indicate that retinoic acid (RA) appears dispensable for the transition of premeiotic to meiotic spermatocytes, meiosis, and spermiogenesis. They confirm that RA plays critical roles in controlling spermatogonia differentiation, spermatid adhesion to Sertoli cells, and spermiation, and suggest that the VAD-induced arrest of spermatogonia differentiation results from simultaneous blocks in RA-dependent events mediated by RA receptor ␥ (RAR␥) in spermatogonia and by RAR␣ in Sertoli cells. They also provide evidence that expression of major RA-metabolizing enzymes is increased in mouse Sertoli cells upon VAD and that vitamin A-deficient A spermatogonia differ from their RA-sufficient counterparts by the expression of the Stra8 gene.

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“…CYP26A1 and CYP26B1 also increase in some tissues when the concentration of RA rises ( 21 ). Conversely, in the situation of VA defi ciency, when the concentration of RA is very low, LRAT is downregulated ( 22 ), and CYP26 is maintained at a very low level ( 23,24 ). Therefore, to a certain extent, the self-regulatory mechanisms involving RA render the body able to modulate its retinol metabolism and thus to avoid both VA deficiency and toxicity.…”

Section: Gene Mrna Level Determinationmentioning

confidence: 99%

Acidic retinoids synergize with vitamin A to enhance retinol uptake and STRA6, LRAT, and CYP26B1 expression in neonatal lung

Ross

2010

Journal of Lipid Research

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This article is available online at http://www.jlr.org but unlike VA, which is stored in tissues as retinyl ester (RE) and mobilized to produce RA ( 4 ), no signifi cant amount of RA is stored and the pool of RA turns over rapidly ( 5 ). RA and other retinoids have been shown to enhance alveolar septation in neonatal rats and mice (as reviewed in Refs. 2,3,6,7 ) and in some cases to improve lung repair after injury in adults ( 3,8,9 ). Most of the VA present in the lungs is in the form of RE ( 10-12 ). In fullterm infants, a process of signifi cant RE accumulation in the lungs has begun from the third trimester of fetal life, after which the stored RE becomes quickly depleted during late gestation and early postnatal life ( 10 ). By contrast, preterm infants often have low VA status at birth ( 13-15 ), which may contribute to poor lung maturation and increased susceptibility to respiratory diseases ( 16 ). Therefore, ways to improve RE storage in the lungs in the postnatal period could be useful clinically for supporting retinoid-requiring metabolic functions and aiding postnatal lung development.Previously, we tested a combination of VA (retinol) and RA, referred to as VARA (10:1 molar mixture of VA and RA) as an oral supplement for promoting lung RE formation ( 12 ). Lung RE increased synergistically, at least 4-fold more than for an equal amount of VA alone ( 17 ). As RA is not reduced to retinol in vivo and thus is not a substrate for tissue RE synthesis, the increase in RE in the lungs implies that RA plays a regulatory role in this organ, in some manner facilitating RE formation. The synergistic effect of VARA was selective for the lungs, as RE formation in the liver did not differ between VARA and an equal dose of VA only ( 12,17 ). In a metabolic study using [ 3 H]retinol to trace the uptake of newly absorbed retinol, we found that RA served to direct more of the [ 3 H]retinol tracer and, thus, the oral VA supplement, into the neonatal lung ( 12 ).Abstract Vitamin A (VA) is essential for fetal lung development and postnatal lung maturation. VA is stored mainly as retinyl esters (REs), which may be mobilized for production of retinoic acid (RA). This study was designed 1 ) to evaluate several acidic retinoids for their potential to increase RE in the lungs of VA-supplemented neonatal rats, and 2 ) to determine the expression of retinoid homeostatic genes related to retinol uptake, esterifi cation, and catabolism as possible mechanisms. When neonatal rats were treated with VA combined with any one of several acidic retinoids (RA, 9-cis -RA, or Am580, a stable analog of RA), lung RE increased ‫ف‬ 5-7 times more than after an equal amount of VA alone. Retinol uptake and esterifi cation during the period of absorption correlated with increased expression of both STRA6 (retinol-binding protein receptor) and LRAT (retinol esterifi cation), while a reduction in RE after 12 h in Am580-treated, VA-supplemented rats correlated with a strong and persistent increase in CYP26B1 (RA hydroxylase). We conclude that neona...

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Cloning of rat cytochrome P450RAI (CYP26) cDNA and regulation of its gene expression by all-trans-retinoic acid in vivo

Cited by 76 publications

References 37 publications

Pharmacokinetics of the time-dependent elimination of all-trans-retinoic acid in rats

Pharmacokinetics of the time-dependent elimination of all-trans-retinoic acid in rats

Retinoids and spermatogenesis: Lessons from mutant mice lacking the plasma retinol binding protein

Acidic retinoids synergize with vitamin A to enhance retinol uptake and STRA6, LRAT, and CYP26B1 expression in neonatal lung

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