Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of growth hormone (GH) and retinoids on P4502C7 mRNA levels were investigated in cultured primary hepatocytes from normal female rats. Northern blot analysis of total nucleic acids from hepatocytes maintained in culture for 90 hr showed low basal levels of P4502C7 mRNA, which were marginally increased after continuous treatment with GH. Retinal treatment gave a slightly higher induction than GH, whereas treatment with all-trans retinoic acid alone or with GH in combination with retinol induced P4502C7 mRNA to levels about one-third of those in normal female rat liver. The effects of retinoids on P4502C7 mRNA were dependent on both the dose and type of retinoid used. All-trans retinoic acid produced a saturable dose-response curve with a 50% maximal induction of P4502C7 mRNA at 1.5 microM. The isomer 9-cis retinoic acid showed a dose-dependent activation of P4502C7 mRNA similar to that of all-trans retinoic acid. Retinol gave a 50% maximal response at approximately 5 microM. In the presence of GH, the induction of P4502C7 mRNA appeared additive to the effect of retinol at all concentrations used and to all-trans retinoic acid at concentrations up to 1 microM. As determined by a quantitative solution hybridization assay, P4502C7 mRNA levels were induced 3-fold by GH, 5-fold by retinol, and 19-fold by all-trans retinoic acid. In the presence of GH, P4502C7 was induced 8-fold by retinol, whereas the induction by saturating concentration of all-trans retinoic acid showed no significant additional effect of GH. The importance of vitamin A for the expression of P4502C7 in vivo was confirmed by the low abundance of P4502C7 mRNA in vitamin A-deficient animals as compared with vitamin A-adequate control rats. Nuclear run-on experiments performed in cultured primary hepatocytes showed that both GH and retinoic acid exert their effects at the transcriptional level. We conclude that both GH and retinoids can induce P4502C7 mRNA in rat liver hepatocytes, retinoic acid being the dominant inducer.
Mol Pharmacol 1993 Nov
PMID:Growth hormone and vitamin A induce P4502C7 mRNA expression in primary rat hepatocytes. 824 23

The regeneration of visual pigment in rod photoreceptors of the vertebrate retina requires an exchange of retinoids between the neural retina and the retina pigment epithelium (RPE). It has been hypothesized that interphotoreceptor retinoid-binding protein (IRBP) functions as a two-way carrier of retinoid through the aqueous compartment (interphotoreceptor matrix) that separates the RPE and the photoreceptors. The first part of this review summarizes the cellular and molecular biology of IRBP. Work on the IRBP gene indicates that the protein contains a four-fold repeat structure that may be involved in binding multiple retinoid and fatty acid ligands. These repeats and other aspects of the gene structure indicate that the gene has had an active and complex evolutionary history. IRBP mRNA is detected only in retinal photoreceptors and in the pineal gland; expression is thus restricted to the two photosensitive tissues of vertebrate organisms. In the second part of this review, we consider the results obtained in experiments that have examined the activity of IRBP in the process of visual pigment regeneration. We also consider the results obtained on the bleaching and regeneration of rhodopsin in the acutely detached retina, as well as in experiments testing the ability of IRBP to protect its retinoid ligand from isomerization and oxidation. Taken together, the findings provide evidence that, in vivo, IRBP facilitates both the delivery of all-trans retinol to the RPE and the transfer of 11-cis retinal from the RPE to bleached rod photoreceptors, and thereby directly supports the regeneration of rhodopsin in the visual cycle.
Mol Neurobiol 1993
PMID:Interphotoreceptor retinoid-binding protein (IRBP). Molecular biology and physiological role in the visual cycle of rhodopsin. 831 67

We have previously reported metabolic cooperation between Sertoli and peritubular myoid cells in terms of synthesis of one of the main testicular extracellular matrix (ECM) constituents, glycosaminoglycans (GAG). This study concerns Sertoli cell ECM-peritubular myoid cell interactions in terms of GAG synthesis. We have examined the responses of hormones and other regulatory agents such as a combination of follicle-stimulating hormone (FSH), insulin, retinol, and testosterone (FIRT) on peritubular myoid cells, and tested if Sertoli cell ECM or serum factor substitute for the stimulation by FIRT. Testicular peritubular myoid cells cultured on Sertoli cell ECM showed significant increases in the levels of cell- and ECM-associated GAG over that when cultured on uncoated plastic. This indicates a specific cell-substratum interaction between Sertoli cell ECM and peritubular myoid cells in the testis in terms of GAG synthesis. Moreover, in terms of cell-associated GAG synthesis, peritubular myoid cell cultured on Sertoli cell ECM or on plastic in the presence of serum substituted for the stimulatory response of FIRT on peritubular myoid cells cultured on uncoated plastic. The data are discussed in relation to the possible role of cell-substratum interaction in maintaining peritubular myoid cell functions.
Mol Reprod Dev 1993 Jun
PMID:Rat Sertoli cell extracellular matrix regulates glycosaminoglycan synthesis by peritubular myoid cells in vitro. 831 20

The in vitro enzymatic conversion of beta-carotene to retinal by partially purified preparations from the intestinal mucosa of sheep, goats and cattle was demonstrated. At pH 7.8 and 37 degrees C, this enzyme from sheep, goats and cattle displayed Michaelis-Menten type kinetics with a Vmax (nmol substrate split/mg protein/h) of 0.21, 0.27, and 0.04 and an apparent Km of 4.66 x 10(-6) M, 13.4 x 10(-6) M and 1.27 x 10(-6) M respectively. Maximal reaction was obtained by addition of an appropriate combination of detergent and bile salt, sodium dodecyl sulphate and egg lecithin. The cattle enzyme was inhibited by sodium glycocholate. The activity of sheep enzyme was higher (P < 0.05) than that of goats and cattle. The measured activity of the preparations from sheep, goats and cattle grazed on the same pasture reflected their contents of the reaction product, retinol, in the liver.
Biochem Mol Biol Int 1993 Jun
PMID:A comparison of beta-carotene-splitting activity isolated from intestinal mucosa of pasture-grazed sheep, goats and cattle. 836 4

This paper reviews characteristics of microsomal membrane structure; long chain fatty acids, acyl CoA derivatives, retinoids and the microsomal formation of acyl CoA derivatives and retinyl esters. It is analyzed how the movement of these molecules at the intracellular level is affected by their respective binding proteins (Fatty acid binding protein, acyl CoA binding protein and cellular retinol binding protein). Studies with model systems using these hydrophobic ligands and the lipid-binding or transfer proteins are also described. This topic is of interest especially because in the esterification of retinol the three substrates and the three binding proteins may interact.
Mol Cell Biochem 1993 Mar 24
PMID:Interaction of fatty acids, acyl-CoA derivatives and retinoids with microsomal membranes: effect of cytosolic proteins. 838 30

The x-ray crystal structures of normal human transthyretin (prealbumin) and the amyloidogenic Val-30-Met variant have been refined at 1.7-A resolution to R-values of 0.168 and 0.179, respectively, for 19,882 and 20,362 reflections (Fobs > 2.0 sigma). Standard deviations for stereochemical parameters are 0.018 and 0.022 A for bond distances, 0.030 and 0.038 A for angle distances, and 0.035 and 0.070 A for planar 1-4 distances. The newly refined normal structure shows improvement over the original structure of Blake and Swan (Blake, C. C. F., and Swan, I. D. A. (1971) J. Mol. Biol. 61, 217-224) in stereochemistry and in the conformation of the loop regions. Residues Arg-103, Thr-123, Asn-124, and Pro-125 have now been resolved, and residues 1-9 and 126-127 have been modeled with the aid of simulated annealing refinement. The functional form of transthyretin is a tetramer, having a cylindrical cavity which will bind thyroxine and an exterior binding site for the complex of retinol with retinol-binding protein. The monomer is a beta barrel flattened to become more like a sandwich with residue 30 in the interior. The methionyl for valyl substitution forces the beta sheets of the monomer as much as 1 A apart, resulting in a distortion of the thyroxine-binding cavity, in agreement with the independent observations that the Met-30 variant has low affinity for thyroxine.
 ...
PMID:The x-ray crystal structure refinements of normal human transthyretin and the amyloidogenic Val-30-->Met variant to 1.7-A resolution. 842 15

The three-dimensional structures of the liganded and unliganded forms of human plasma retinol binding protein (RBP) in the trigonal crystal form have been solved at 2.5 A resolution. The final model of RBP complexed with retinol (holoRBP, space group R3, a = b = 104.0 A, c = 74.4 A) has a crystallographic R factor of 0.176 for 9652 reflections. The unliganded form, obtained through a purification procedure which included steps based on hydrophobic interaction chromatography, crystallized isomorphously with holoRBP and its structure has been refined to an R factor of 0.190 for 9614 reflections. The structure of the trigonal holo protein is quite similar to that of the orthorhombic form: the root-mean-square deviation of all the equivalent alpha-carbons in the two chains is 0.53 A. The structural comparison between the liganded and unliganded forms of RBP in the crystal did not reveal gross conformational changes. The most significant difference between the two forms of the protein is a conformational change involving residues from 34 to 37. In this region, the movements of side-chains of Leu35 and Phe36 are most noticeable. In particular, in the unliganded form the side-chain ring of the latter residue is in the place previously occupied by the alcoholic moiety of retinol. Our data are consistent with a model in which a region comprising these residues and at least part of the opening of the beta-barrel is involved in the recognition between RBP and transthyretin. In the case of the unliganded form, the central cavity, that is occupied by the vitamin in the two human crystalline holoRBPs, is filled by electron density that, at the present resolution, we interpret as solvent.
J Mol Biol 1993 Mar 20
PMID:Crystal structure of the trigonal form of human plasma retinol-binding protein at 2.5 A resolution. 846 67

Vitamin A and calcium are important regulators of growth and differentiation of epithelial cells and are intimately involved in preneoplastic and neoplastic transformation. It has been proposed that their effects are mediated by autocrine/paracrine positive and negative regulators of growth. The objectives of this investigation were to examine the effects of all-trans retinoic acid (RA) and Ca2+ on cell proliferation, anchorage-independent growth (AIG), and on the expression of transforming growth factor-alpha (TGF-alpha), transforming growth factor-beta 1 (TGF-beta 1), and p53 tumor suppressor genes in human tracheal gland epithelial (HTGE) cells immortalized by adenovirus 12-simian virus 40 (Ad12-SV40) hybrid. Cells exhibiting the transformed phenotype, AIG, were maintained in serum-free culture conditions. Calcium effects were examined at 0.15, 0.50, 1.0, and 2.0 mM concentrations. The effects of RA were determined with 10(-9), 10(-7), and 10(-6) M concentrations. Gene expression was examined by Northern and Western analyses. Ca2+ had no significant effect on cell proliferation, but it enhanced the expression of TGF-beta 1 gene and slightly inhibited p53 expression. Ca2+ had no effect on TGF-alpha. RA inhibited both cell proliferation and AIG growth, which was accompanied by enhanced expression of p53. RA had no significant effect on the expression of TGF-alpha and TGF-beta 1 genes. These results demonstrate that RA regulates growth of HTGE cells mainly by upregulating the p53 gene; Ca2+, which enhances TGF-beta 1 expression, had no effect on growth.
Am J Respir Cell Mol Biol 1993 Apr
PMID:Retinoic acid and calcium regulation of p53, transforming growth factor-beta 1, and transforming growth factor-alpha gene expression and growth in adenovirus 12-SV40-transformed human tracheal gland epithelial cells. 847 34

Apo and holo-cellular retinol-binding protein II have been crystallized, and their crystal structures have been determined to 2.1 A and 1.9 A respectively. The apo and holo-crystals have different but related triclinic space groups. The X-ray phases for both structures were determined using the molecular replacement method. The crystal co-ordinates were refined to an R-factor of 0.200 for apo, and 0.173 for holo-cellular retinol-binding protein II. The holo and apo-models have nearly the same tertiary structures. Cellular retinol-binding protein II consists of a ten-stranded anti-parallel beta-barrel with the ligand binding cavity within the barrel. Two alpha-helices cover the open end of the beta-barrel making it almost solvent inaccessible. A single portal large enough to admit a water molecule was observed opening into the binding cavity. Exogenously added retinol was found within the cavity of each holo-cellular retinol-binding protein II molecule. Each retinol was surrounded by both polar and non-polar residues. The hydroxyl group of the bound retinol hydrogen bonds to the amide group of glutamine 108. The overall conformation of the bound retinol was derived from the four different molecules of holo-cellular retinol-binding protein II present in the triclinic form. The four copies of bound retinol had essentially the same conformation as found in crystalline retinaldehyde.
J Mol Biol 1993 Apr 20
PMID:Crystal structures of holo and apo-cellular retinol-binding protein II. 848 3

Androst-4-ene-3,17-dione (androstenedione) was found to be a potent competitive inhibitor of the NADH-supported reduction of retinal in rat hepatic microsomes (Ki 42 microM, Km/Ki ratio 1.1). Similarly, the NADH-mediated reduction of androstenedione was inhibited in mixed fashion by retinal (Ki 12 microM, Km/Ki ratio 0.34). In subsequent experiments the cofactor NADH exhibited an identical Km (8 microM) in the microsomal reductions of both substrates. Acidic pH markedly stimulated the microsomal reduction of androstenedione to testosterone and was also found to enhance retinal reduction to retinol, although the latter reaction exhibited a distinct pH optimum between 6.0 and 6.5. These results suggest that a common enzyme may participate in the reduction of both substrates but at least one other enzyme probably participates in hepatic microsomal testosterone production.
J Steroid Biochem Mol Biol 1993 Jun
PMID:Kinetic evidence for the involvement of a common enzyme in the microsomal reduction of retinal and androstenedione in rat liver. 851 13


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>