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)

Retinol (Vitamin A) has been found to inhibit the stimulation of lymphocytes by certain mitogens. The ultrastructural morphology of phytohaemagglutinin-stimulated lymphocytes exposed to retinol 10 microgram/ml and 20 microgram/ml show that disaggregation of polyribosomes and formation of autophagic vacuoles ensue in the majority of the cells. Some of the lymphocyte clumps are unaffected and continue to show normal mitosis. The changes in the affected cell are similar to those seen in a cell undergoing hormonal involution and it is postulated that the effects of the retinol may be mediated by a retinol binding protein in the susceptible cells.
Virchows Arch B Cell Pathol Incl Mol Pathol 1979 Oct
PMID:The effect of retinol (vitamin A) on human lymphocytes stimulated by phytohaemagglutinin. An ultrastructural study. 4 8

Three independent mutations of Phycomyces blakesleeanus resulting in overaccumulation of beta-carotene are recessive and belong to the same complementation group. The corresponding gene has been named carS. Evidence is presented that gene carS is not the same as gene carA, previously defined by mutations blocking carotene production. Vitamin A increases carotenogenesis in wild types and in carS mutants to about the same extent. Intersexual heterokaryosis increases carotenogenesis most prominently in carS genetic backgrounds (up to 300 times the production of the wild type in the same conditions). Vitamin A, intersexual heterokaryosis and carS mutations are thought to stimulate carotenogenesis through different mechanisms. It is suggested that the carS gene product participates in end-product regulation of the pathway.
Mol Gen Genet 1976 Oct 18
PMID:Regulation of carotene synthesis in Phycomyces. 99 22

Mammalian alcohol dehydrogenase (ADH) catalyzes the oxidation of retinol to retinaldehyde, the rate-limiting step in the synthesis of retinoic acid. There exists a family of ADH isozymes encoded by unique genes, and it is unclear which isozymes are most important for regulation of retinoic acid synthesis during differentiation or development. A region in the human ADH3 promoter from -328 to -272 base pairs was shown previously to function as a retinoic acid response element (RARE), prompting an hypothesis for a positive feedback mechanism controlling retinoic acid synthesis (Duester, G., Shean, M. L., McBride, M. S., and Stewart, M. J. (1991) Mol. Cell. Biol. 11, 1638-1646). The ADH3 RARE contains three direct AGGTCA repeats which constitute the critical nucleotides of RAREs present in other genes. We dissected the ADH3 RARE and determined that receptor binding as well as transactivation are dependent upon only the two downstream AGGTCA motifs separated by 5 base pairs, a structure noticed previously for a RARE in the promoter for the retinoic acid receptor beta (RAR beta) gene. ADH3 and RAR beta RAREs functioned similarly in transfection assays, suggesting that the feedback mechanisms controlling ADH3 and RAR beta utilize a common RARE. We also found that the normal functioning of the ADH3 RARE was abrogated by thyroid hormone receptor in the presence of thyroid hormone. A negative thyroid hormone response element in the human ADH3 promoter was found to colocalize with the RARE. Since ADH production in rat liver is known to be repressed by thyroid hormone, these findings suggest that human ADH production may also be subject to thyroid hormone repression and that the mechanism involves an interference with retinoic acid induction.
 ...
PMID:Retinoic acid activation and thyroid hormone repression of the human alcohol dehydrogenase gene ADH3. 132 Nov 36

One of the monoclonal antibodies raised against bovine beta-lactoglobulin reacted with human serum retinol binding protein. The finding that this monoclonal antibody also reacted with the serum retinol binding proteins isolated from other animals, suggested that this epitopic conformation is conserved among these proteins. Using ELISA and various synthetic peptides of defined sequence, we show in this paper that the epitope defined by this monoclonal antibody comprises of the highly conserved core sequence of DTDY present in beta-lactoglobulin and retinol binding proteins.
Mol Immunol 1992 Apr
PMID:A common epitope of beta-lactoglobulin and serum retinol-binding proteins: elucidation of its core sequence using synthetic peptides. 137 68

The structure of the unligated recombinant human cyclophilin A (CyP A) has been refined to an R-factor of 0.18 at 1.63 A resolution. The root-mean-squared deviations of the refined structure are 0.013 A and 2.50 degrees from ideal geometries of bond length and bond angle, respectively. Eight antiparallel beta-strands of CyP A form a right-handed beta-barrel. The structure of CyP A is compared with other members in the antiparallel eight-stranded beta-barrel family and with the parallel eight-stranded alpha/beta barrels. Although all known eight-stranded barrels are right-handed, the tilted angle of the strands against the barrel axis varies from 45 degrees for retinol binding protein and 49 degrees for CyP A to 70 degrees for superoxide dismutase. As a result, the beta-barrel of CyP A is not completely superimposable with other members of beta-barrels. The structure of CyP A has a unique topology, distinct from other members in the beta-barrel family. In addition, CyP A is a closed beta-barrel so that neither the immunosuppressive drug cyclosporin A (CsA) nor the proline-containing substrate can bind to the hydrophobic core of the CyP A barrel, while the hydrophobic core of most other barrels is open for ligation. These observations probably indicate that CyP A is neither functionally nor evolutionally related to other beta-barrel structures. Details of interactions between solvent molecules and the active site residues of CyP A are illustrated. A water-co-operated mechanism, where the cis<-->trans isomerization might possibly consist of (1) transition of the prolyl bond and (2) release of N or C-terminal residues of substrate from CyP, is addressed. The refined structure reveals no disulfide bridges in CyP A. Cys115 is near the CsA site, but unlikely to be directly involved in CsA binding because of steric hindrance from Thr119 and Leu122. This geometry probably rules out any mechanisms involving a tetrahedral intermediate formed between cysteine and substrate during cis<-->trans isomerization.
J Mol Biol 1992 Nov 20
PMID:Similarities and differences between human cyclophilin A and other beta-barrel structures. Structural refinement at 1.63 A resolution. 145 63

Vitamins contain reactive functional groups necessary to their established roles as coenzymes and reducing agents. Their reactive potential may produce injury if vitamin concentration, distribution, or metabolism is altered. However, identification of vitamin toxicity has been difficult. The only well-established human vitamin neurotoxic effects are those due to hypervitaminosis A (pseudotumor cerebri) and pyridoxine (sensory neuropathy). In each case, the neurological effects of vitamin deficiency and vitamin excess are similar. Closely related to the neurological symptoms of hypervitaminosis A are symptoms including headache, pseudotumor cerebri, and embryotoxic effects reported in patients given vitamin A analogs or retinoids. Most tissues contain retinoic acid (RA) and vitamin D receptors, members of a steroid receptor superfamily known to regulate development and gene expression. Vitamin D3 effects on central nervous system (CNS) gene expression are predictable, in addition to the indirect effects owing to its influence on calcium and phosphorus homeostasis. Folates and thiamine cause seizures and excitation when administered in high dosage directly into the brain or cerebrospinal fluid (CSF) of experimental animals but have rarely been reported to cause human neurotoxicity, although fatal reactions to i.v. thiamine are well known. Ascorbic acid influences CNS function after peripheral administration and influences brain cell differentiation and 2-deoxyglucose accumulation by cultured glial cells. Biotin influences gene expression in animals that are not vitamin-deficient and alters astrocyte glucose utilization. The multiple enzymes and binding proteins involved in regeneration of retinal vitamin A illustrate the complexity of vitamin processing in the body. Vitamin A toxicity is also a good general model of vitamin neurotoxicity, because it shows the importance of the ratio of vitamin and vitamin-binding proteins in producing vitamin toxicity and of CNS permeability barriers. Because vitamin A and analogs enter the CNS better than most vitamins, and because retinoids have many effects on enzyme activity and gene expression, Vitamin A neurotoxicity is more likely than that of most, perhaps all other vitamins. Megadose vitamin therapy may cause injury that is confused with disease symptoms. High vitamin intake is more hazardous to peripheral organs than to the nervous system, because CNS vitamin entry is restricted. Vitamin administration into the brain or CSF, recommended in certain disease states, is hazardous and best avoided. The lack of controlled trials prevents us from defining the lowest human neurotoxic dose of any vitamin. Large differences in individual susceptibility to vitamin neurotoxicity probably exist, and ordinary vitamin doses may harm occasional patients with genetic disorders.(ABSTRACT TRUNCATED AT 400 WORDS)
Mol Neurobiol 1992
PMID:Vitamin neurotoxicity. 146 88

The affinity of purified human vitamin D-binding protein from serum (DBP) for 25-hydroxyvitamin D3 (25-OHD3) and 1 alpha,25-dihydroxyvitamin D3 [1,25-(OH)2D3] was measured in the presence of free fatty acids (FFA), cholesterol, prostaglandins and several drugs. Mono- and polyunsaturated fatty acids markedly decreased the affinity of both 25-OHD3 and 1,25-(OH)2D3 for DBP, whereas saturated fatty acids (stearic and arachidic acid), cholesterol, cholesterol esters, retinol, retinoic acid and prostaglandins (A1 and E1) did not affect the apparent affinity. Several chemicals known to decrease the binding of thyroxine to its plasma-binding protein did not affect the affinity of DBP. The apparent affinity of DBP for both 25-OHD3 and 1,25-(OH)2D3 decreased 2.4- to 4.6-fold in the presence of 36 microM of linoleic or arachidonic acid, respectively. Only a molar ratio of FFA:DBP higher than 10,000 was able to decrease the binding of 25-OHD3 to DBP by 20%. Much smaller ratio's of FFA:DBP (25 for arachidonic and 45 for oleic acid), however, decreased the binding of 1,25-(OH)2D3 to DBP. These latter ratio's are well within the physiological range. The addition of human albumin in a physiological albumin:DBP molar ratio did not impair the inhibitory effect of linoleic acid on the binding of [3H]25-OHD3 to DBP. The binding and bioavailability of vitamin D metabolites thus might be altered by mono- and polyunsaturated but not by saturated fatty acids.
J Steroid Biochem Mol Biol 1992 Sep
PMID:Polyunsaturated fatty acids decrease the apparent affinity of vitamin D metabolites for human vitamin D-binding protein. 152 46

The metabolism of retinoic acid, retinol, and retinal has been investigated with eight purified rabbit cytochrome P-450 (P-450) isozymes, including the major forms in nasal and liver microsomes. Retinoids hydroxylated at the 4-position were found to be major metabolites with each of the isozymes examined. Only two of the isozymes, polycyclic aromatic hydrocarbon-inducible P-450 1A2 and antibiotic-inducible P-450 3A6, also catalyze the oxidation of retinal to retinoic acid, a reaction not previously attributed to P-450. P-450 1A2 showed high activities in both the 4-hydroxylation and aldehyde oxidation reactions. Phenobarbital-inducible P-450 2B4 also had high activity in the 4-hydroxylation reaction of retinoids, and cytochrome b5 was found to increase the activity of P-450 2B4 with each substrate but to increase the activity of P-450 1A2 only with retinoic acid. In microsomes, retinoic acid is converted in an NADPH-dependent manner to both 4-hydroxyretinoic acid and 4-oxoretinoic acid, but none of the isozymes investigated was found to convert the 4-hydroxy derivative to the 4-oxo derivative. Microsomes from animals treated with phenobarbital were more active than those from untreated animals in the 4-hydroxylation reaction and, consequently, showed an increase in the ratio of 4-hydroxy to 4-oxo derivatives produced. These results show that the individual forms of P-450 metabolize retinoic acid, retinol, and retinal to multiple products, and they indicate that the amounts formed may be dependent on the exposure of animals to various inducers of P-450.
Mol Pharmacol 1992 Feb
PMID:Role of isozymes of rabbit microsomal cytochrome P-450 in the metabolism of retinoic acid, retinol, and retinal. 153 19

We have studied collagen synthesis and secretion in an established liver connective tissue cell line (GRX) that can be induced in vitro to express either the myofibroblastic or the fat-storing (lipocyte) phenotype. In lipocytes, collagen synthesis was reduced. Their intracellular collagen degradation corresponded to 15% of newly synthesized collagen. In myofibroblasts, collagen synthesis was high but its secretion was considerably altered by intracellular collagen degradation, which attained up to 60% of newly synthesized collagen. In this in vitro model, we have provided direct evidence that hepatic lipocytes, involved mainly in lipid and retinol metabolism, have a low basal level of collagen synthesis. Myofibroblastic phenotype correlates with increased collagen synthesis and may be directly related to increased collagen deposition in hepatic fibrosis. Modulation of the phenotype of liver connective tissue cells are possibly one of the major points of control in normal and pathological deposition of collagen in liver parenchyma.
Exp Mol Pathol 1992 Apr
PMID:Collagen synthesis in an established liver connective tissue cell line (GRX) during induction of the fat-storing phenotype. 158 37

A three-dimensional model for the complex between human serum retinol binding protein and transthyretin (formerly named prealbumin) is presented. The model was obtained by interactive rigid-body computer graphics docking and the characterization of the molecular surfaces in terms of fractal dimension. Available experimental data, as well as results from molecular dynamics calculations, support the proposed model.
J Mol Graph 1992 Jun
PMID:A molecular model for the retinol binding protein-transthyretin complex. 163 49


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