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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

F9 embryonic teratocarcinoma stem cells differentiate into an epithelial cell type called extraembryonic endoderm when treated with retinoic acid (RA), a derivative of retinol (vitamin A). This differentiation is presumably mediated through the actions of retinoid receptors, the RARs and RXRs. To delineate the functions of each of the different retinoid receptors in this model system, we have generated F9 cell lines in which both copies of either the RAR alpha gene or the RAR gamma gene are disrupted by homologous recombination. The absence of RAR alpha is associated with a reduction in the RA-induced expression of both the CRABP-II and Hoxb-1 (formerly 2.9) genes. The absence of RAR gamma is associated with a loss of the RA-inducible expression of the Hoxa-1 (formerly Hox-1.6), Hoxa-3 (formerly Hox-1.5), laminin B1, collagen IV (alpha 1), GATA-4, and BMP-2 genes. Furthermore, the loss of RAR gamma is associated with a reduction in the metabolism of all-trans-RA to more polar derivatives, while the loss of RAR alpha is associated with an increase in metabolism of RA relative to wild-type F9 cells. Thus, each of these RARs exhibits some specificity with respect to the regulation of differentiation-specific gene expression. These results provide an explanation for the expression of multiple RAR types within one cell type and suggest that each RAR has specific functions.
Mol Cell Biol 1995 Feb
PMID:Targeted disruption of retinoic acid receptor alpha (RAR alpha) and RAR gamma results in receptor-specific alterations in retinoic acid-mediated differentiation and retinoic acid metabolism. 782 50

The effect of retinol deficiency and curcumin and turmeric feeding on brain microsomal Na(+)-K(+)ATPase activity was investigated. The brain Na(+)-K(+)ATPase activity registered an increase of 148.5% as compared to the control group. Upon treating retinol deficient rats with curcumin or turmeric, the abnormally elevated activity showed a decrease of 36.9 and 47.1%, respectively, when compared to the retinol deficient group. An increase in Vmax by 67% and Km by 66% for ATP was observed in the retinol deficient group. Curcumin or turmeric fed retinol-deficient groups reduced the Vmax by 25 and 33%, while Km was reduced by 25 and 31%, respectively, compared to the retinol deficient group. Arrhenius plot of Na(+)-K(+) ATPase showed a typical bi-phasic pattern in all the groups. Cholesterol:Phospholipid ratio showed a decrease in the retinol-deficient group by 67.8%, which showed a marked increase in curcumin or turmeric treated groups. Detergents could increase the Na(+)-K(+) ATPase activity more in the control group than in the retinol deficient groups. Curcumin or turmeric improved the detergent action on the enzyme. Subsequent freezing and thawing over a period of 30 min decreased the enzyme activity by 22.8% in the retinol deficient group compared to 15.9% decrease in the control group. Curcumin or turmeric treated groups showed a decrease in the enzyme activity by 22.0 and 19.2%, respectively, when compared to the zero time in each group. In the presence of concanavalin-A (Con-A) there was only 52.4% stimulation in the enzyme activity in retinol deficient groups, compared to 108.0% in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Biochem 1994 Aug 31
PMID:Effect of retinol deficiency and curcumin or turmeric feeding on brain Na(+)-K+ adenosine triphosphatase activity. 784 84

Previous results from our laboratory gave evidence that safe doses of vitamin A were very effective in protecting rats from adriamycin-induced oxidative stress and lethal cardiotoxicity (Tesoriere, L. et al. (1994) J. Pharmacol. Experim. Ther. 269, 430-436). This was an incentive also to evaluate whether or not vitamin A affected the antitumor activity of adriamycin. K562 human erythroleukemia cells were exposed to adriamycin or to adriamycin plus vitamin A. Presence of 2.5 to 15 microM all-trans retinol in the cell culture did not impair the cytotoxicity of adriamycin. Rather, an enhanced cell death was observed when cell colony was exposed to both compounds. Additional assays showed that all-trans retinol counteracted the lipoperoxide formation, assayed as malondialdehyde, induced in cell cultures by the redox cycling activity of adriamycin. These data strongly encourage a new therapeuthical approach with safe doses of vitamin A as an adjuvant in cancer chemotherapy.
Biochem Mol Biol Int 1994 Sep
PMID:Vitamin A preserves the cytotoxic activity of adriamycin while counteracting its peroxidative effects in human leukemic cells in vitro. 784 45

Vitamin A is an important factor during gestation and its metabolite, retinoic acid (RA), is a potent teratogen. However, RA action on the placenta is still poorly understood. In this study we analysed the presence of RARs and RXRs in human trophoblastic cells. We determined that RAR alpha was the more expressed form in term placenta, and that RAR beta was induced by RA treatment. Then we analysed RA effects on endocrine activities and on epidermal growth factor (EGF) receptor expression. We found that RA decreased 125I-labeled EGF binding and EGF-dependent phosphorylation. Furthermore, RA treatment led to a concentration-dependent decrease in the amount of EGFR protein expression. This treatment also decreased EGF receptor mRNA levels, suggesting transcriptional regulation of the EGF receptor. Thus we demonstrated that RA could interact with feto-placental development by modulating trophoblast EGF receptors expression, probably via its nuclear receptors.
Mol Cell Endocrinol 1994 Nov
PMID:Nuclear retinoic acid receptor characterization in cultured human trophoblast cells: effect of retinoic acid on epidermal growth factor receptor expression. 785 22

Free radical oxidation has been claimed as one of the most important mechanism of damage in aging and in several diseases. Carbonyl content in tissue and circulating proteins is a stable marker of this attack. In 29 apparently healthy subjects (25-89 years old) carbonyl content of plasma proteins and retinol and tocopherols (alpha- and gamma-) were studied. Carbonyls level did not show an increase with age. A good correlation between carbonyls content and gamma-tocopherol (r = 0.44, P < 0.05) and a trend with retinol (r = 0.34, P = 0.07) was found, but not with alpha-tocopherol. An inverse correlation was observed between carbonyls and plasma proteins (r = -0.63, P < 0.01) and the natural antioxidant studied showed an increase with age and a good relationship with lipids. These data suggest that retinol and tocopherols, well known scavengers of free radicals, are involved, at least partially, in the prevention of oxidative damage of circulating proteins.
Biochem Mol Biol Int 1994 Oct
PMID:Relationships between protein carbonyls, retinol and tocopherols level in human plasma. 786 99

Vitamin A is a potent regulator of testicular function. We have reported that retinol (R) and retinoic acid (RA) induced a down regulation of luteinizing hormone/human chorionic gonadotropin (LH/CG) binding sites in K9 Leydig cells. In the present study we evaluated the effect of R and RA on LH/CG receptors, cholesterol side-chain cleavage cytochrome P-450 (P-450 scc), 17 alpha-hydroxylase/C17-20 lyase (P-450 17 alpha) and 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) mRNA levels in K9 mouse Leydig cells. To validate K9 cells as a model for studying Leydig cell steroidogenesis at the molecular level, we first investigated the effect of hCG on mRNA levels of the steroidogenic enzymes. P-450 scc, 3 beta HSD and P-450 17 alpha were expressed constitutively. The addition of 10 ng/ml hCG enhanced mRNA levels for the three genes within 2 h. Maximal accumulation of P-450 scc, P-450 17 alpha and 3 beta HSD mRNA in treated cells represents a 2.5-, 8.5- and 4-fold increase over control values, respectively. P-450 17 alpha expression reached a maximum by 4 h and then declined rapidly to return to control value by 24 h. The pattern of LH/CG receptor mRNAs in K9 cells was very similar to that of MA10 Leydig cells and showed six transcripts of 1.1, 1.6, 1.9, 2.6, 4.2 and 7.0 kb. Treatment of cells with R or RA resulted in a time- and dose-dependent decrease in all six species.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1994 Dec
PMID:Regulation by retinoids of luteinizing hormone/chorionic gonadotropin receptor, cholesterol side-chain cleavage cytochrome P-450, 3 beta-hydroxysteroid dehydrogenase/delta (5-4)-isomerase and 17 alpha-hydroxylase/C17-20 lyase cytochrome P-450 messenger ribonucleic acid levels in the K9 mouse Leydig cell line. 789 12

The Adh-1 gene product, ADH-A2, the only known murine class I alcohol dehydrogenase, is able to oxidize retinol (vitamin A) into retinaldehyde, the first enzymatic step in the conversion of retinol into its biologically active metabolite retinoic acid. We have investigated the developmental expression pattern of Adh-1 transcripts by in situ hybridization. Transcripts were first detected by embryonic day 10.5 in the mesonephros mesenchyme. During the following gestational days, Adh-1 transcripts were detected in several mesenchymal areas, such as nasal, laterocervical, and genital regions. Adh-1 transcripts were also detected in a small ectodermal domain at the anterior margins of both forelimbs and hindlimbs. During late fetal development. Adh-1 transcripts were found essentially in the epidermis and in a number of tissues which continue to express the gene after birth, such as liver, kidney, gut epithelium, adrenal cortex, testis interstitium, and ovarian stroma. In contrast, a strong expression of Adh-1 was found in the mesenchyme of developing lungs, but not in the adult organ. This highly regulated expression of Adh-1 is discussed with respect to the local synthesis of retinoic acid during development. Although the promoter of the human counterpart of Adh-1 contains a retinoic acid response element (Duester et al. [1991] Mol. Cell. Biol. 11:1638-1646), we report that this element is not conserved in the murine gene. Consistently, Adh-1 promoter-containing reporter constructs were not retinoic acid-inducible in cotransfections assays with RARs and/or RXRs, suggesting that retinoic acid regulation of Adh-1 differs from that of the human gene.
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PMID:Stage and tissue-specific expression of the alcohol dehydrogenase 1 (Adh-1) gene during mouse development. 801 87

Changes in the steady state level of retinols, retinaldehydes and retinyl esters in the trans and 11-cis forms and trans retinoic acid were measured in whole chicken eye during development from day 6 in ovo to day 3 post-hatch. These retinoids, quantified by different HPLC systems, were detected in this time sequence: trans-retinol and trans-retinyl esters in the first week in ovo, 11-cis-retinol in the second week. The highest level of 11-cis-retinaldehyde and 11-cis-retinyl esters was reached at the end of development in ovo; however, their levels increased further after hatching. The retinoic acid level decreased at the end of the first week, rising again at the end of the second week. The enzyme activities involved in the metabolism of these retinoids-acyl-CoA: retinol acyltransferase, trans-retinol dehydrogenase, 11-cis-retinol dehydrogenase, trans-retinyl ester hydrolase and trans: 11-cis-retinol isomerase were also estimated and they were detectable already in the first week of development in ovo. At day 6 of the biosynthesis of retinoic acid by the retinaldehyde dehydrogenase activity from retina cytosol was also shown.
Mol Cell Biochem 1994 Mar 16
PMID:Retinoid dynamics in chicken eye during pre- and postnatal development. 807 8

The functional role of airway mucin in the respiratory system is well recognized. The isolation of mucin cDNA clones, MUC genes, introduces new information regarding the structure of the mucin core protein; however, the nature of the authentic core protein of airway mucin is still unresolved. In this communication, the effects of vitamin A on the regulation of MUC2 gene expression in primary tracheobronchial epithelial (TBE) cells of human and nonhuman primates were examined. Vitamin A has been recognized as one of the most important nutrients in the regulation of airway mucous cell differentiation. The expression of the MUC2 gene has been demonstrated in both rat and human tracheal tissues. The monkey cDNA clone MT80 was isolated from a cDNA library derived from vitamin A-depleted cultures of monkey TBE cells using a synthetic oligonucleotide probe corresponding to the 69 nucleotides of a tandemly repeated sequence in human MUC2 cDNA. DNA sequencing revealed a similar tandemly repeated sequence, except that 72 oligonucleotide repeats were observed in the monkey cDNA clone. Using the MT80 cDNA as a probe, the expression of the MUC2 gene was studied in vitro. The corresponding MUC2 message level in primary cultures of monkey TBE cells was down-regulated by vitamin A. This result was consistently demonstrated in primary human and hamster TBE cultures. The down-regulation was both time- and dosage-dependent on vitamin A. A nuclear run-on assay demonstrated a decrease in the transcriptional rate of the MUC2 gene in nuclei isolated from vitamin A-treated cultures. These results suggest that MUC2 gene expression in TBE cells is transcriptionally down-regulated by vitamin A.
Am J Respir Cell Mol Biol 1994 May
PMID:Expression of MUC2 gene is down-regulated by vitamin A at the transcriptional level in vitro in tracheobronchial epithelial cells. 817 18

The cellular fatty acid-binding proteins (FABP) and cellular retinoid (retinol, retinoic acid)-binding proteins (CRtBP) are structurally and functionally-defined groups within an evolutionarily conserved gene family. CRtBP are expressed in both fully differentiated and developing tissues in a manner that supports a relationship to the action of retinoic acid in morphogenesis and cellular differentiation. The FABP are, by contrast, expressed only in fully differentiated tissues in a manner compatible with a major function in the metabolism of long-chain fatty acids (LCFA) for energy production or storage. The precise function(s) of FABP and CRtBP remain imperfectly understood, while subspecialization of function(s) within the two groups is suggested by the complex diversity in both of structurally distinct members that display striking tissue and temporal specificity of expression in addition to ligand specificity. Notwithstanding this considerable apparent functional diversity among the FABP and CRtBP, available evidence supports a dual set of generic functions for both protein groups in a) promoting cellular flux of poorly water-soluble ligands and their subsequent metabolic utilization or transformation, and b) sequestration of ligands in a manner that limits their association with alternative binding sites within the cell, of which members of the steroid hormone nuclear receptor superfamily (HNR) are a potentially important category. Theoretical as well as experimental models probing diffusional fluxes of LCFA in vitro and in living cells have provided support for a function for FABP in intracellular LCFA transport. Protein-bound ligand also appears to provide the substrate for metabolic transformation of retinoids bound to CRtBP, but convincing evidence is lacking for an analogous mechanism in the direct facilitation of fatty acid utilization by FABP. An emerging relationship between FABP and CRtBP function centers on their binding of, and induction by, ligands which activate or transform specific HNR-the retinoic acid receptors and the peroxisome proliferator activated receptor in the case of CRtBP and FABP, respectively. Evidence consistent with both a 'promotive' role (provision of ligands for HNR) and a 'protective' role (limiting availability of free ligand for HNR association) has been advanced for CRtBP. Available data supports a 'protective' function for cellular retinoic acid-binding proteins (CRABP) and liver FABP (L-FABP) and points to the existence of ligand-defined, lipid-binding-protein-HNR relationships in which CRABP serve to attenuate the induction of gene expression by retinoic acid, and in which L-FABP may modulate a cellular adaptive multigene response to increased LCFA flux or compromised LCFA utilization.(ABSTRACT TRUNCATED AT 400 WORDS)
Mol Cell Biochem
PMID:Cellular binding proteins for fatty acids and retinoids: similar or specialized functions? 823 63


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