scholarly journals A biologically active metabolite of retinoic acid from rat liver

1965 ◽  
Vol 97 (1) ◽  
pp. 180-186 ◽  
Author(s):  
M Zile ◽  
HF Deluca
Keyword(s):  
Retinoic Acid ◽  
Methyl Ester ◽  
Vitamin A ◽  
Active Metabolite ◽  
Active Form ◽  
Active Material ◽  
Biologically Active ◽  
Growth Assay ◽  
Hydrolysis Of ◽  
Acidic Compound

1. Four major radioactive fractions have been isolated from the livers of vitamin A-deficient rats given [6,7-(14)C(2)]retinoic acid. 2. At least one of these was more potent than retinoic acid and approximately equal to retinol in the growth assay for vitamin A activity. 3. The biologically active material was chromatographically distinct from retinoic acid, retinol and retinal. 4. Alkaline hydrolysis of this material yielded an acidic compound containing all the radioactivity. 5. The methyl ester of the acidic product was unlike the methyl ester of retinoic acid in its chromatographic behaviour. 6. It is suggested that this metabolite may represent the active form of retinol in its growth-supporting role.

scholarly journals Regulation of Hepatitis C Virus Infection by Cellular Retinoic Acid Binding Proteins through the Modulation of Lipid Droplet Abundance

2019 ◽  
Vol 93 (8) ◽  
Author(s):  
Bo-Ram Bang ◽  
Meng Li ◽  
Kuen-Nan Tsai ◽  
Haruyo Aoyagi ◽  
Shin-Ae Lee ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Life Cycle ◽  
Hepatitis C ◽  
Vitamin A ◽  
Active Metabolite ◽  
Antiviral Effect ◽  
Biologically Active ◽  
Viral Pathogens ◽  
Intrinsic Mechanism ◽  
Retinoic Acid Binding Proteins

ABSTRACTRetinoid (vitamin A) is an essential diet constituent that governs a broad range of biological processes. Its biologically active metabolite, all-transretinoic acid (ATRA), exhibits a potent antiviral property by enhancing both innate and adaptive antiviral immunity against a variety of viral pathogens, such as, but not limited to, HIV, respiratory syncytial virus (RSV), herpes simplex virus (HSV), and measles. Even though the hepatocyte is highly enriched with retinoid and its metabolite ATRA, it supports the establishment of efficient hepatitis C virus (HCV) replication. Here, we demonstrate the hepatocyte-specific cell-intrinsic mechanism by which ATRA exerts either a proviral or antiviral effect, depending on how it engages cellular retinoic acid binding proteins (CRABPs). We found that the engagement of CRABP1 by ATRA potently supported viral infection by promoting the accumulation of lipid droplets (LDs), which robustly enhanced the formation of a replication complex on the LD-associated endoplasmic reticulum (ER) membrane. In contrast, ATRA binding to CRABP2 potently inhibited HCV via suppression of LD accumulation. However, this antiviral effect of CRABP2 was abrogated due to the functional and quantitative predominance of CRABP1 in the hepatocytes. In summary, our study demonstrates that CRABPs serve as an on-off switch that modulates the efficiency of the HCV life cycle and elucidates how HCV evades the antiviral properties of ATRA via the exploitation of CRABP1 functionality.IMPORTANCEATRA, a biologically active metabolite of vitamin A, exerts pleiotropic biological effects, including the activation of both innate and adaptive immunity, thereby serving as a potent antimicrobial compound against numerous viral pathogens. Despite the enrichment of hepatocytes with vitamin A, HCV still establishes an efficient viral life cycle. Here, we discovered that the hepatocellular response to ATRA creates either a proviral or an antiviral environment depending on its engagement with CRABP1 or -2, respectively. CRABP1 supports the robust replication of HCV, while CRABP2 potently inhibits the efficiency of viral replication. Our biochemical, genetic, and microscopic analyses reveal that the pro- and antiviral effects of CRABPs are mediated by modulation of LD abundance, where HCV establishes the platform for viral replication and assembly on the LD-associated ER membrane. This study uncovered a cell-intrinsic mechanism by which HCV exploits the proviral function of CRABP1 to establish an efficient viral life cycle.

scholarly journals Studies on the relative biopotencies and intestinal absorption of different apo-β-carotenoids in rats and chickens

1976 ◽  
Vol 158 (2) ◽  
pp. 377-383 ◽  
Author(s):  
R V Sharma ◽  
S N Mathur ◽  
J Ganguly
Keyword(s):  
Retinoic Acid ◽  
Methyl Ester ◽  
Vitamin A ◽  
Intestinal Absorption ◽  
Free Acid ◽  
Beta Carotene ◽  
Weight Basis ◽  
Molar Basis ◽  
Growth Assay ◽  
Liver Storage

1. The biopotencies relative to beta-carotene of several apocarotenoids, such as 8′-, 10′- and 12′-apo-beta-carotenal and methyl 8′-apo-beta-carotenoate, were investigated in rats, on a molar basis, by both curative-growth assay and liver-storage tests. 2. In the curative-growth assays, on a molar basis the biopotencies of 8′-, 10′- and 12′-apo-beta-carotenal and methyl 8′-apo-beta-carotenoate were 72, 78, 72 and 53% respectively, whereas on a weight basis the corresponding values were 93, 111, 111 and 63%, with respect to beta-carotene taken as 100%. In terms of yield of vitamin A, these values were much lower in the liver-storage tests. 3. When 8′-apo-beta-carotenal was fed, the unchanged aldehyde together with small amounts of the corresponding alcohol and larger proportions of the acid rapidly appeared in the tissues of both rats and chickens. The 8′-apocarotenol, 8′-apocarotenoic acid and its methyl ester were absorbed unchanged. The free acid disappeared most rapidly from the tissues, but its methyl ester persisted in the tissues longest. 4. On the basis of these observations it is suggested that most of an apocarotenal is oxidized to the corresponding acid, which, in turn, is mostly degraded to retinoic acid, with small proportions of it being attacked by the dioxygenase system giving retinal.

scholarly journals A new approach to the assessment of marginal vitamin A deficiency in children in suburban Guwahati, India: hydrolysis of retinoyl glucuronide to retinoic acid

2008 ◽  
Vol 101 (6) ◽  
pp. 794-797 ◽  
Author(s):  
Pulin C. Sarma ◽  
Bhabesh C. Goswami ◽  
Krishna Gogoi ◽  
Harsha Bhattacharjee ◽  
Arun B. Barua
Keyword(s):  
Retinoic Acid ◽  
Vitamin A ◽  
Vitamin A Deficiency ◽  
Serum Retinol ◽  
Serum Samples ◽  
Group I ◽  
High Prevalence ◽  
Hydrolysis Of ◽  
Β Carotene

The objective of the present study was to determine marginal vitamin A deficiency (VAD) by testing the hydrolysis of retinoyl glucuronide (RAG) to retinoic acid (RA) in children. Previous studies in rats showed that hydrolysis occurred when rats were vitamin A deficient. Children (n 61) aged 3–18 years, were divided into two groups, I and II. Blood was collected from the children in Group I (n 19) who were not dosed with RAG. Children in Group II (n 42) were administered all-trans retinoyl glucuronide (RAG) orally, and blood was collected 4 h after the dose. All serum samples were analysed for retinoids and carotenoids. RA was detected in serum only when serum retinol was < 0·85 μmol/l. Thus, hydrolysis of RAG to RA occurred in children with VAD or marginal VAD. Serum retinol was < 0·35 μmol/l in twenty-one children, 0·35–0·7 μmol/l in twenty-three children, 0·7–0·9 μmol/l in eleven children and >1 μmol/l in six children. Mean serum retinol in sixty-one children was 0·522 (sd 0·315) μmol/l. Mean β-carotene (0·016 (sd 0·015) μmol/l) was far below normal compared to the level of lutein (0·176 (sd 0·10) μmol/l) in sixty-one children. A low β-carotene level might be due to a low intake of carotene but high demand for vitamin A. The RAG hydrolysis test may prove to be a useful approach for the determination of marginal VAD with no clinical or subclinical signs of VAD. High prevalence of VAD amongst certain communities in Assam cannot be ruled out.

Molecular approaches to vertebrate limb morphogenesis

Development ◽  
1989 ◽  
Vol 107 (Supplement) ◽  
pp. 121-131 ◽  
Author(s):  
Susan M. Smith ◽  
Kevin Pang ◽  
Olof Sundin ◽  
Sarah E. Wedden ◽  
Christina Thaller ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Cell Fate ◽  
Retinoic Acid Receptor ◽  
Active Form ◽  
Mirror Image ◽  
Biologically Active ◽  
Molecular Approaches ◽  
Limb Morphogenesis ◽  
Order Of Magnitude ◽  
Temporal Expression Pattern

It has long been proposed that concentration gradients of morphogens provide cues to specify cell fate in embryonic fields. Recent work in a variety of vertebrate systems give bona fide evidence that retinoic acid, the biologically active form of vitamin A, is a candidate for such a morphogen. In the developing chick wing, for example, locally applied retinoic acid triggers striking changes in the pattern along the anteroposterior axis. Instead of giving rise to a wing with the normal 234 digit pattern, wing buds treated with retinoic acid develop a 432234 mirror-image symmetrical digit pattern. For this review, we focus on three aspects of limb morphogenesis. (1) We summarize the experimental evidence supporting the notion that retinoic acid is a candidate morphogen. (2) Limb buds contain high levels of cellular retinoic-acid-binding protein (CRABP). Using order of magnitude calculations, we evaluate how the concentration of CRABP might affect the occupancy state of the retinoic acid receptor. (3) We discuss the spatio-temporal expression pattern of homeobox-containing genes in the developing limb and speculate about the possibility that retinoic acid influences the pattern of expression of homeobox genes.

scholarly journals De Novo-Synthesized Retinoic Acid in Ovarian Antral Follicles Enhances FSH-Mediated Ovarian Follicular Cell Differentiation and Female Fertility

Endocrinology ◽  
2016 ◽  
Vol 157 (5) ◽  
pp. 2160-2172 ◽  
Author(s):  
Tomoko Kawai ◽  
Noriyuki Yanaka ◽  
JoAnne S. Richards ◽  
Masayuki Shimada
Keyword(s):  
Retinoic Acid ◽  
Vitamin A ◽  
Chorionic Gonadotropin ◽  
Granulosa Cells ◽  
Human Chorionic Gonadotropin ◽  
De Novo ◽  
Active Form ◽  
Developmental Competence ◽  
Deficient Diet ◽  
Equine Chorionic Gonadotropin

Abstract Retinoic acid (RA) is the active form of vitamin A and is synthesized from retinol by two key enzymes, alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH). As the physiological precursor of RA, retinol impacts female reproductive functions and fertility. The expression of Adh1 and Adh5 as well as Aldh1a1 and Aldh1a7 are significantly increased in the ovaries of mice treated with equine chorionic gonadotropin/FSH. The RA receptor is expressed and localized in granulosa cells and is activated by endogenous RA as indicated by LacZ expression in granulosa cells of RA-responsive transgene-LacZ transgenic mice (RA reporter mice). Coinjection of the ADH inhibitor, 4-methylpyrazole, with equine chorionic gonadotropin significantly decreases the number and developmental competence of oocytes ovulated in response to human chorionic gonadotropin/LH as compared with controls. Injections of RA completely reverse the effects of the inhibitor of ovulation and oocyte development. When mice were fed a retinol-free, vitamin A-deficient diet that significantly reduced the serum levels of retinol, the expression of the LH receptor (Lhcgr) was significantly lower in the ovaries of the vitamin A-deficient mice, and injections of human chorionic gonadotropin failed to induce genes controlling ovulation. These results indicate that ovarian de novo biosynthesis of RA is required for the follicular expression of Lhcgr in granulosa cells and their ability to respond to the ovulatory LH surge.

scholarly journals Priming with Retinoic Acid, an Active Metabolite of Vitamin A, Increases Vitamin A Uptake in the Small Intestine of Neonatal Rats

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4275
Author(s):  
Yaqi Li ◽  
Cheng-Hsin Wei ◽  
J. Kalina Hodges ◽  
Michael H. Green ◽  
A. Catharine Ross
Keyword(s):  
Retinoic Acid ◽  
Vitamin A ◽  
Oral Dose ◽  
Canola Oil ◽  
Active Metabolite ◽  
Storage Capacity ◽  
Treatment Time ◽  
Neonatal Rats ◽  
Continuous Increase ◽  
Second Peak

Given that combined vitamin A (VA) and retinoic acid (RA) supplementation stimulated the intestinal uptake of plasma retinyl esters in neonatal rats, we administrated an RA dose as a pretreatment before VA supplementation to investigate the distinct effect of RA on intestinal VA kinetics. On postnatal days (P) 2 and 3, half of the pups received an oral dose of RA (RA group), while the remaining received canola oil as the control (CN). On P4, after receiving an oral dose of 3H-labeled VA, pups were euthanized at selected times (n = 4–6/treatment/time) and intestine was collected. In both CN and RA groups, intestinal VA mass increased dramatically after VA supplementation; however, RA-pretreated pups had relatively higher VA levels from 10 h and accumulated 30% more VA over the 30-h study. Labeled VA rapidly peaked in the intestine of CN pups and then declined from 13 h, while a continuous increase was observed in the RA group, with a second peak at 10 h and nearly twice the accumulation of 3H-labeled VA compared to CN. Our findings indicate that RA pretreatment may stimulate the influx of supplemental VA into the intestine, and the increased VA accumulation suggests a potential VA storage capacity in neonatal intestine.

Isolation and identification of 5,6-epoxyretinoic acid: a biologically active metabolite of retinoic acid

Biochemistry ◽  
1978 ◽  
Vol 17 (19) ◽  
pp. 4085-4090 ◽  
Author(s):  
Anne M. McCormick ◽  
Joseph L. Napoli ◽  
Heinrich K. Schnoes ◽  
Hector F. DeLuca
Keyword(s):  
Retinoic Acid ◽  
Active Metabolite ◽  
Biologically Active ◽  
Isolation And Identification

scholarly journals Leukocyte Homing, Fate, and Function Are Controlled by Retinoic Acid

2015 ◽  
Vol 95 (1) ◽  
pp. 125-148 ◽  
Author(s):  
Yanxia Guo ◽  
Chrysothemis Brown ◽  
Carla Ortiz ◽  
Randolph J. Noelle
Keyword(s):  
Retinoic Acid ◽  
Vitamin A ◽  
Immune Cell ◽  
Active Form ◽  
Cell Lineage ◽  
Vitamin A Metabolism ◽  
Immune Cell Subsets ◽  
Development And Differentiation ◽  
And Function ◽  
Leukocyte Homing

Although vitamin A was recognized as an “anti-infective vitamin” over 90 years ago, the mechanism of how vitamin A regulates immunity is only beginning to be understood. Early studies which focused on the immune responses in vitamin A-deficient (VAD) animals clearly demonstrated compromised immunity and consequently increased susceptibility to infectious disease. The active form of vitamin A, retinoic acid (RA), has been shown to have a profound impact on the homing and differentiation of leukocytes. Both pharmacological and genetic approaches have been applied to the understanding of how RA regulates the development and differentiation of various immune cell subsets, and how RA influences the development of immunity versus tolerance. These studies clearly show that RA profoundly impacts on cell- and humoral-mediated immunity. In this review, the early findings on the complex relationship between VAD and immunity are discussed as well as vitamin A metabolism and signaling within hematopoietic cells. Particular attention is focused on how RA impacts on T-cell lineage commitment and plasticity in various diseases.

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