scholarly journals Inflammation induced by lipopolysaccharide does not prevent the vitamin A and retinoic acid-induced increase in retinyl ester formation in neonatal rat lungs

2012 ◽  
Vol 109 (10) ◽  
pp. 1739-1745 ◽  
Author(s):  
Lili Wu ◽  
A. Catharine Ross
Keyword(s):  
Gene Expression ◽  
Retinoic Acid ◽  
Vitamin A ◽  
Retinol Binding Protein ◽  
Neonatal Rat ◽  
Control Group ◽  
Retinyl Ester ◽  
Protein Receptor ◽  
Ester Formation ◽  
Lecithin:Retinol Acyltransferase

Vitamin A (VA) plays an important role in post-natal lung development and maturation. Previously, we have reported that a supplemental dose of VA combined with 10 % of all-trans-retinoic acid (VARA) synergistically increases retinol uptake and retinyl ester (RE) storage in neonatal rat lung, while up-regulating several retinoid homeostatic genes including lecithin:retinol acyltransferase (LRAT) and the retinol-binding protein receptor, stimulated by retinoic acid 6 (STRA6). However, whether inflammation has an impact on the expression of these genes and thus compromises the ability of VARA to increase lung RE content is not clear. Neonatal rats, 7- to 8-d-old, were treated with VARA either concurrently with lipopolysaccharide (LPS; Expt 1) or 12 h after LPS administration (Expt 2); in both studies, lung tissue was collected 6 h after VARA treatment, when RE formation is maximal. Inflammation was confirmed by increased IL-6 and chemokine (C–C motif) ligand 2 (CCL2) gene expression in lung at 6 h and C-reactive protein in plasma at 18 h. In both studies, LPS-induced inflammation only slightly reduced, but did not prevent the VARA-induced increase in lung RE. Quantitative RT-PCR showed that co-administration of LPS with VARA slightly attenuated the VARA-induced increase of LRAT mRNA, but not of STRA6 or cytochrome P450 26B1, the predominant RA hydroxylase in lung. By 18 h post-LPS, expression had subsided and none of these genes differed from the level in the control group. Overall, the present results suggest that retinoid homeostatic gene expression is reduced modestly, if at all, by acute LPS-induced inflammation and that VARA is still effective in increasing lung RE under conditions of moderate inflammation.

scholarly journals Opposing actions of cellular retinol-binding protein and alcohol dehydrogenase control the balance between retinol storage and degradation

2004 ◽  
Vol 383 (2) ◽  
pp. 295-302 ◽  
Author(s):  
Andrei MOLOTKOV ◽  
Norbert B. GHYSELINCK ◽  
Pierre CHAMBON ◽  
Gregg DUESTER
Keyword(s):  
Retinoic Acid ◽  
Vitamin A ◽  
Alcohol Dehydrogenase ◽  
Retinol Binding Protein ◽  
Dietary Vitamin ◽  
Gene Encoding ◽  
Retinyl Ester ◽  
Ester Formation ◽  
Retinyl Esters ◽  
Cellular Retinol Binding Protein

Vitamin A homoeostasis requires the gene encoding cellular retinol-binding protein-1 (Crbp1) which stimulates conversion of retinol into retinyl esters that serve as a storage form of vitamin A. The gene encoding alcohol dehydrogenase-1 (Adh1) greatly facilitates degradative metabolism of excess retinol into retinoic acid to protect against toxic effects of high dietary vitamin A. Crbp1−/−/Adh1−/− double mutant mice were generated to explore whether the stimulatory effect of CRBP1 on retinyl ester formation is due to limitation of retinol oxidation by ADH1, and whether ADH1 limits retinyl ester formation by opposing CRBP1. Compared with wild-type mice, liver retinyl ester levels were greatly reduced in Crbp1−/− mice, but Adh1−/− mice exhibited a significant increase in liver retinyl esters. Importantly, relatively normal liver retinyl ester levels were restored in Crbp1−/−/Adh1−/− mice. During vitamin A deficiency, the additional loss of Adh1 completely prevented the excessive loss of liver retinyl esters observed in Crbp1−/− mice for the first 5 weeks of deficiency and greatly minimized this loss for up to 13 weeks. Crbp1−/− mice also exhibited increased metabolism of a dose of retinol into retinoic acid, and this increased metabolism was not observed in Crbp1−/−/Adh1−/− mice. Our findings suggest that opposing actions of CRBP1 and ADH1 enable a large fraction of liver retinol to remain esterified due to CRBP1 action, while continuously allowing some retinol to be oxidized to retinoic acid by ADH1 for degradative retinoid turnover under any dietary vitamin A conditions.

scholarly journals Multiple cytochrome P-450 genes are concomitantly regulated by vitamin A under steady-state conditions and by retinoic acid during hepatic first-pass metabolism

2011 ◽  
Vol 43 (1) ◽  
pp. 57-67 ◽  
Author(s):  
A. Catharine Ross ◽  
Christopher J. Cifelli ◽  
Reza Zolfaghari ◽  
Nan-qian Li
Keyword(s):  
Gene Expression ◽  
Retinoic Acid ◽  
Steady State ◽  
Vitamin A ◽  
Dynamic Range ◽  
Dynamic Change ◽  
The Body ◽  
Retinol Binding Protein ◽  
Dietary Vitamin ◽  
Wide Range

Vitamin A (retinol) is an essential precursor for the production of retinoic acid (RA), which in turn is a major regulator of gene expression, affecting cell differentiation throughout the body. Understanding how vitamin A nutritional status, as well as therapeutic retinoid treatment, regulates the expression of retinoid homeostatic genes is important for improvement of dietary recommendations and therapeutic strategies using retinoids. This study investigated genes central to processes of retinoid uptake and storage, release to plasma, and oxidation in the liver of rats under steady-state conditions after different exposures to dietary vitamin A (deficient, marginal, adequate, and supplemented) and acutely after administration of a therapeutic dose of all- trans-RA. Over a very wide range of dietary vitamin A, lecithin:retinol acyltransferase (LRAT) as well as multiple cytochrome P-450s (CYP26A1, CYP26B1, and CYP2C22) differed by diet and were highly correlated with one another and with vitamin A status assessed by liver retinol concentration (all correlations, P < 0.05). After acute treatment with RA, the same genes were rapidly and concomitantly induced, preceding retinoic acid receptor (RAR)β, a classical direct target of RA. CYP26A1 mRNA exhibited the greatest dynamic range (change of log 26 in 3 h). Moreover, CYP26A1 increased more rapidly in the liver of RA-primed rats than naive rats, evidenced by increased CYP26A1 gene expression and increased conversion of [3H]RA to polar metabolites. By in situ hybridization, CYP26A1 mRNA was strongly regulated within hepatocytes, closely resembling retinol-binding protein (RBP)4 in location. Overall, whether RA is produced endogenously from retinol or administered exogenously, changes in retinoid homeostatic gene expression simultaneously favor both retinol esterification and RA oxidation, with CYP26A1 exhibiting the greatest dynamic change.

scholarly journals Vitamin A combined with retinoic acid increases retinol uptake and lung retinyl ester formation in a synergistic manner in neonatal rats

2006 ◽  
Vol 47 (8) ◽  
pp. 1844-1851 ◽  
Author(s):  
A. Catharine Ross ◽  
Namasivayam Ambalavanan ◽  
Reza Zolfaghari ◽  
Nan-qian Li
Keyword(s):  
Retinoic Acid ◽  
Vitamin A ◽  
Neonatal Rats ◽  
Retinyl Ester ◽  
Ester Formation

187 9-cis RETINOIC ACID IMPROVES MATURATION RATE AND ALTERS GENE EXPRESSION OF IN VITRO-MATURED OOCYTES IN EGYPTIAN BUFFALO

2017 ◽  
Vol 29 (1) ◽  
pp. 202
Author(s):  
A. Gad ◽  
S. Abu Hamed ◽  
M. Khalifa ◽  
A. El-Sayed ◽  
S. A. Swiefy ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Retinoic Acid ◽  
Vitamin A ◽  
Oocyte Maturation ◽  
In Vitro Maturation ◽  
Polar Body ◽  
Control Group ◽  
Maturation Rate

Retinoic acid, a metabolite of vitamin A, regulates oocyte maturation through multiple mechanisms, including gene expression modulation or preventing oxidative stress. Effects of retinoic acid during oocyte maturation have been reported in several species; however, there have been no studies illustrating these effects in buffalo. Therefore, the objective of this study was to investigate the influence of 9-cis retinoic acid (9-cisRA), an active metabolite of vitamin A, on maturation rate and gene expression during in vitro maturation of buffalo oocytes. Cumulus-oocyte complexes (n = 360) were aspirated from surface follicles of Buffalo ovaries collected from local abattoirs and transported to the laboratory in physiological saline (0.9% NaCl) containing antibiotics (100 µg mL−1 of streptomycin sulfate and 100 IU mL−1 of penicillin) and maintained at 30°C. Grade A cumulus-oocyte complexes (evenly granulated cytoplasm and surrounded by multiple layers of cumulus cells) were randomly divided into 4 groups (90 oocytes/group) and allocated in TCM-199 medium supplemented with 10% fetal bovine serum, 0.2 mM sodium pyruvate, 50 μg mL−1 of gentamycin, and 10 μg mL−1 of FSH and contained 0 (control), 5, 50, or 200 nM of 9-cisRA for maturation. After 24 h, maturation rate was calculated as a percentage based on polar body extrusion. In addition, gene expression patterns were analysed for antioxidant related genes (SOD1, CAT, GPX4, HOMX1, and PRDX1) and oocyte quality-related genes (GDF9 and BMP15) using quantitative real-time PCR with GAPDH as a housekeeping gene. Fold changes (FC) were calculated using ΔΔCt method (FC ≥2; P < 0.05). The results showed that maturation rate (based on the extrusion of polar body) was significantly higher in 5 nM 9-cisRA oocyte group (49.4 ± 2.1%) compared with the control group (35 ± 1.8%); in contrast, the 200 nM 9-cisRA oocyte group showed the lowest maturation rate (27.2 ± 2.7%). However, the 50 nM 9-cisRA oocyte group showed no significant differences (31.2 ± 3.8%) compared with control group .Oocytes treated with 5 and 50 nM 9-cisRA during in vitro maturation showed significant up-regulation of SOD1 (3.4 and 3.08 FC), CAT (2.7 and 1.8 FC), and HOMX1 (4.5 and 4 FC), and significant down-regulation of BMP15 (−3.7 and −3.6 FC), respectively, compared with the control group. Moreover, GPX4, PRDX1, and GDF9 genes were highly expressed in the 50 nM compared with the control group (13.2, 10.4, and 1.8 FC, respectively). In contrast, the 200 nM 9-cisRA group showed significant down-regulation of CAT (−60.3 FC), GDF9 (−2.5 FC), and BMP15 (−9.7 FC) compared with the control group. In conclusion, these results suggested that a low concentration of 9-cisRA (5 nM) in maturation media can improves maturation rate of buffalo oocytes and up-regulates the expression of oxidative stress response-related genes.

scholarly journals Multiple pathways ensure retinoid delivery to milk: studies in genetically modified mice

2010 ◽  
Vol 298 (4) ◽  
pp. E862-E870 ◽  
Author(s):  
Sheila M. O'Byrne ◽  
Yuko Kako ◽  
Richard J. Deckelbaum ◽  
Inge H. Hansen ◽  
Krzysztof Palczewski ◽  
...  
Keyword(s):  
Normal Growth ◽  
Retinyl Palmitate ◽  
Postnatal Period ◽  
Retinol Binding Protein ◽  
Wild Type ◽  
Retinyl Ester ◽  
Ester Formation ◽  
Fatty Acid Transporter ◽  
Retinyl Esters ◽  
Lecithin:Retinol Acyltransferase

Retinoids are absolutely required for normal growth and development during the postnatal period. We studied the delivery of retinoids to milk, availing of mouse models modified for proteins thought to be essential for this process. Milk retinyl esters were markedly altered in mice lacking the enzyme lecithin:retinol acyltransferase ( Lrat−/−), indicating that this enzyme is normally responsible for the majority of retinyl esters incorporated into milk and not an acyl-CoA dependent enzyme, as proposed in the literature. Unlike wild-type milk, much of the retinoid in Lrat−/− milk is unesterified retinol, not retinyl ester. The composition of the residual retinyl ester present in Lrat−/− milk was altered from predominantly retinyl palmitate and stearate to retinyl oleate and medium chain retinyl esters. This was accompanied by increased palmitate and decreased oleate in Lrat−/− milk triglycerides. In other studies, we investigated the role of retinol-binding protein in retinoid delivery for milk formation. We found that Rbp−/− mice maintain milk retinoid concentrations similar to those in matched wild-type mice. This appears to arise due to greater postprandial delivery of retinoid, a lipoprotein lipase (LPL)-dependent pathway. Importantly, LPL also acts to assure delivery of long-chain fatty acids (LCFA) to milk. The fatty acid transporter CD36 also facilitated LCFA but not retinoid incorporation into milk. Our data show that compensatory pathways for the delivery of retinoids ensure their optimal delivery and that LRAT is the most important enzyme for milk retinyl ester formation.

The Effect of Vitamin A Supplementation on Retinoic Acid-Related Orphan Receptor γt (RORγt) and Interleukin-17 (IL-17) Gene Expression in Avonex-Treated Multiple Sclerotic Patients

2013 ◽  
Vol 51 (3) ◽  
pp. 749-753 ◽  
Author(s):  
Niyaz Mohammadzadeh Honarvar ◽  
Mohammad Hossein Harirchian ◽  
Fariba Koohdani ◽  
Feridoun Siassi ◽  
Mina Abdolahi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Retinoic Acid ◽  
Vitamin A ◽  
Orphan Receptor ◽  
Interleukin 17 ◽  
Vitamin A Supplementation

scholarly journals Effect of biscuits fortified with different doses of vitamin A on indices of vitamin A status, haemoglobin and physical growth levels of pre-school children in Chongqing

2010 ◽  
Vol 13 (9) ◽  
pp. 1462-1471 ◽  
Author(s):  
Xuan Zhang ◽  
Ke Chen ◽  
Ping Qu ◽  
You-Xue Liu ◽  
Ting-Yu Li
Keyword(s):  
Vitamin A ◽  
School Children ◽  
Vitamin A Deficiency ◽  
Daily Intake ◽  
Retinol Binding Protein ◽  
Physical Growth ◽  
Control Group ◽  
Group I ◽  
Significant Difference ◽  
Different Doses

AbstractObjectiveTo investigate the efficacy of biscuits fortified with different doses of vitamin A on improving vitamin A deficiency (VAD), anaemia and physical growth of pre-school children.DesignA randomised double-masked population-based field interventional trial with a positive control group.SettingBanan district of Chongqing, China.SubjectsA total of 580 pre-school children aged 3–6 years were randomly recruited into four groups. Children in groups I and II were given biscuits fortified with vitamin A at 30 % of the recommended daily intake (RDA) and 100 % of the RDA once a day for 9 and 3 months, respectively. Children in group III received biscuits containing 20 000 IU of vitamin A once a week for 3 months. Initially, the children in group IV received a 200 000 IU vitamin A capsule just once. At the beginning and end of the study, blood samples were collected to measure Hb, serum retinol, retinol-binding protein and prealbumin, and weight and height were measured.ResultsAll the fortification types significantly decreased the prevalence of VAD and anaemia in each group (P < 0·05). The effect of 9-month intervention on group I was the most efficient (P < 0·0045). After intervention, the Z-scores of height-for-age, weight-for-age and weight-for-height in all groups increased markedly compared with baseline (P < 0·05), but no significant difference was observed among the groups.ConclusionsData indicated that consuming vitamin A-fortified biscuits with daily 100 % RDA for 3 months has the same effect on the improvement of VAD, anaemia and physical growth as did the weekly 20 000 IU and single 200 000 IU administration in pre-school children.

scholarly journals Effect of retinoid status on α, β and γ retinoic acid receptor mRNA levels in various rat tissues

1992 ◽  
Vol 286 (3) ◽  
pp. 755-760 ◽  
Author(s):  
S Kato ◽  
H Mano ◽  
T Kumazawa ◽  
Y Yoshizawa ◽  
R Kojima ◽  
...  
Keyword(s):  
Gene Expression ◽  
Vitamin D ◽  
Retinoic Acid ◽  
Thyroid Hormone ◽  
Vitamin A ◽  
Retinoic Acid Receptor ◽  
Rat Tissues ◽  
Mrna Levels ◽  
Acid Receptor ◽  
Beta Gene

We have investigated the effects of retinoids, vitamin D and thyroid hormone on the levels of retinoic acid receptor (RAR)alpha, RAR beta and RAR gamma mRNAs in intact animals. Although vitamin A deficiency caused no significant changes in the levels of RAR alpha and RAR gamma mRNAs, the level of RAR beta transcripts was greatly decreased in various tissues of vitamin A-deficient rats, but was restored rapidly to a normal level after administration of retinoic acid. Retinol also restored the RAR beta mRNA level, but the magnitude and kinetics of the induction differed from those by retinoic acid. The use of specific inhibitors demonstrated that this autoregulation of RAR beta gene expression in vivo occurred at the transcriptional level. In addition, from these results it was postulated that the maintenance of the normal RAR beta mRNA levels seemed to require a threshold serum retinol concentration (about 25 micrograms/dl). Moreover, we found that administration of retinol and retinoic acid to normal rats caused the overexpression of RAR beta transcripts (2-15-fold) when compared with the control levels of RAR beta mRNA, although the levels of RAR alpha and RAR gamma mRNAs were not affected. Vitamin D and thyroid hormone did not modulate the levels of RAR transcripts. These findings clearly indicate the specific ligand regulation of RAR beta gene expression in intact animals. The altered levels of RAR beta according to retinoid status may affect retinoid-inducible gene expression.

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