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

A tumor appeared on the back of a transgenic mouse carrying the SV40 T-antigen under control of a mouse major urinary protein promoter. High levels of mRNA for the mitochondrial uncoupling protein (UCP) indicated that the tumor was a hibernoma. The tumor has been established as a transplantable tumor line in nude (nu/nu) mice and used as a source of cells to develop a tissue culture system for analyzing brown fat development and differentiation. Ucp expression in tumor cells cultured in Dulbecco's modified Eagle's medium and 10% fetal calf serum was virtually undetectable. Addition of 10(-7) M norepinephrine resulted in approximately a 30-fold induction of Ucp mRNA within 4 h. The induction by norepinephrine was independent of cell density and also independent of thyroid hormone and insulin during the first 5 days in culture. However, in order to maintain the inducibility of Ucp during prolonged culture periods, it was necessary to supplement the medium with insulin. In contrast to Ucp, the expression of Gdc-1, which encodes the cytoplasmic glycerol-3-phosphate dehydrogenase and which is also induced in brown fat by cold exposure, was repressed by norepinephrine and induced by the addition of insulin. Characterization of the adrenergic receptors required for Ucp induction with agonists and antagonists indicated that beta 1 receptors are predominantly utilized; there is no evidence for utilization of beta 3 and alpha 1 receptors for Ucp induction.
Mol Endocrinol 1992 May
PMID:Adrenergic regulation of the mitochondrial uncoupling protein gene in brown fat tumor cells. 160 85

Appropriate glycosylation of gonadotropins is essential for the full expression of their biological activity. In this investigation we have compared the properties of glycosylation deficient human chorionic gonadotropin (hCG) produced by chemical deglycosylation (HF treatment--DG-hCG) or recombinant techniques (site directed mutagenesis). Among the recombinant hCG molecules secreted into the culture medium, the following variants containing selective N-glycosylation deletions at delta alpha 1 or delta alpha 1,2 or in both subunits could not stimulate steroidogenesis in mouse Leydig tumor cells (MA-10 cell line) and in this respect were very similar to DG-hCG. The other variants were fully active like native hCG, but the alpha + delta beta 1,2 recombinant hCG was a partial agonist. In radioimmunoassay with antibodies against native hCG, the DG-hCG as well as all recombinant hCG variants, including the wild type (WT), were similar. However, with antisera against DG-hCG or affinity purified antibodies specific to DG-hCG the alpha/delta 1,2 beta mutant, the WT hormone and native hCG were less active. In this assay mutants containing N-glycosylation deletions in the alpha subunit as well as the delta alpha 1,2/delta beta 1,2, variant showed higher activity. A similar pattern was evident in reaction with a selected monoclonal antibody showing preferential binding of 125I-labeled DG-hCG (antagonist). Affinity purified antibody directed against native hCG conformation was successful in converting DG-hCG and some inactive glycosylation deficient variants into an active form by stimulating progesterone in MA-10 cells. These data suggest that there are similarities as well as subtle differences in conformation of DG-hCG and various recombinant hCG molecules.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1992 Jun
PMID:Comparison of the biological and immunological properties of glycosylation deficient human chorionic gonadotropin variants produced by site directed mutagenesis and chemical deglycosylation. 163 18

The transforming growth factors-beta (TGF-beta) affect the metabolic activities of each of the cell types in the ovary. In vitro studies using immature rat ovaries have shown the expression of TGF-beta 1 and/or TGF-beta 2 mRNA in thecal/interstitial cells and in granulosa cells (Mulheron and Schomberg, 1990; Mulheron et al., 1991). To obtain information on the localization of TGF-beta 1 and TGF-beta 2 in the rat ovary in vivo, we have examined the immunohistochemical staining using antibodies specific for either TGF-beta 1 or TGF-beta 2. In the adult ovary the immunostaining for TGF-beta 1 was intense, whereas the staining for TGF-beta 2 was faint. The pattern of immunostaining for TGF-beta 1 and TGF-beta 2 remained constant in the interstitial cell compartment and was not affected by the stage of the oestrous cycle. Since the interstitium surrounds follicles at all stages of development we conclude that TGF-beta is not actively involved in regulating the progression of follicles at discrete stages. At the time of antrum formation in the follicle, intense staining for TGF-beta 1 was observed in thecal cells. Around the preovulatory stage of development, TGF-beta 1 and TGF-beta 2 immunoreactivity was also found in the granulosa cells. In the corpus luteum, intense staining for TGF-beta 1 was found in some areas, whereas other areas were negative. Weak to moderate staining for TGF-beta 2 was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1992 Mar
PMID:Immunohistochemical localization of transforming growth factor-beta 1 and -beta 2 during follicular development in the adult rat ovary. 163 13

gamma-Aminobutyric acid (GABA)-activated Cl- currents in neonatal rat cortical neurons and in cultured cells engineered for the expression of specific molecular forms of the GABAA receptor alpha, beta, and gamma subunits, were recorded with the patch-clamp technique in the whole-cell configuration. The effects of various allosteric modulators of GABAA receptors were determined. Diazepam and clonazepam showed greater efficacy as positive modulators of GABA-elicited currents in alpha 2 beta 1 gamma 2 or alpha 3 beta 1 gamma 2 receptors than in alpha 1 beta 1 gamma 2 or alpha 5 beta 1 gamma 2 receptors or in cortical neurons. Alpidem was more efficacious at alpha 1 beta 1 gamma 2 or alpha 2 beta 1 gamma 2 receptors than at alpha 1 beta 1 gamma 2 or alpha 5 beta 1 gamma 2 receptors or in cortical neurons. Conversely, zolpidem was equally efficacious for all these receptors except for alpha 5 beta 1 gamma 2. Both imidazopyridines (alpidem and zolpidem) were virtually ineffective at modulating the GABA response of alpha 5 beta 1 gamma 2 receptors and in almost all the receptors assembled from alpha 1, alpha 2, alpha 3 or alpha 5 subunits together with beta 1 and gamma 1 subunits. The beta-carboline derivatives methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) and methyl-beta-carboline-3-carboxylate (beta-CCM) elicited a positive allosteric modulation of alpha 1 beta 1 gamma 1 or alpha 2 beta 1 gamma 1 receptors, whereas they acted as negative allosteric modulators at nearly all other receptors tested, as they do in cortical neurons. Although the positive allosteric modulation by beta-carbolines never exceeded a doubling of the GABA response, DMCM was more efficacious at alpha 1 beta 1 gamma 1 receptors and beta-CCM was more efficacious at alpha 2 beta 1 gamma 1 receptors. DMCM was inactive at alpha 3 beta 1 gamma 1 receptors, whereas beta-CCM was virtually inactive at alpha 5 beta 1 gamma 1 receptors. The benzodiazepine 4'-chlorodiazepam, which is a negative modulator resistent to flumazenil inhibition, acted at all the various GABAA receptors that contained a gamma subunit.
Mol Pharmacol 1991 Jun
PMID:Influence of recombinant gamma-aminobutyric acid-A receptor subunit composition on the action of allosteric modulators of gamma-aminobutyric acid-gated Cl- currents. 164 44

Monoclonal antibodies to major histocompatibility complex Class II proteins have been useful probes in understanding both the biochemistry and biology of these proteins. Almost all of the monoclonal antibodies previously described have been produced by immunization of mice with living cells. These antibodies react with native Class II proteins, but not usually with denatured material. It has been difficult to obtain specific anti-Class II antibodies which react with denatured proteins. Antibodies reactive with denatured proteins and with well-defined specificities would be useful in studies of Class II assembly and trafficking during the process of antigen presentation. In order to produce such an antibody we have immunized hamsters with a synthetic peptide corresponding to residues 146-177 (beta 1 domain) of the mouse A beta b protein. An antibody has been produced which reacts with the mouse Class II A beta chain from H-2b, H-2d, H-2p, and H-2q mice in immunoblotting assays, but not with the beta chain from H-2f, H-2j, H-2k or H-2s mice. Comparison of the amino acid sequences of these proteins along with the reactivity patterns of the antibody on synthetic peptides corresponding to homologous regions from A beta b, A beta k, A alpha b and Dp suggest that the region of 153 to 155 is critical for the reactivity of this antibody. This antibody does not react with native Class II protein found on the surface of living mouse cells.
Mol Immunol
PMID:Production and characterization of a peptide specific, anti-major histocompatibility complex class II, monoclonal antibody. 164 72

An experimental method to test the hypothesis that antipsychotic (neuroleptic) agents influence gene expression in the mouse brain has been developed using the cis and trans stereoisomers of flupenthixol. The cis form of the drug is known to be clinically effective against some of the psychotic symptoms of schizophrenia as opposed to the trans isomer which is relatively inactive. A 2- to 3-fold increase in the abundance of dopamine 2 receptor mRNA was observed in the cis treated mice after a period of ten weeks. No change was observed in the expression of the dopamine D2 receptor gene upon treatment with the trans isomer. No change in the amount of 5-HT1A, 5-HT1C, alpha 1 adrenergic, beta 1 and beta 2 adrenergic neuroreceptor mRNA was found in the mice treated with active drug. The results show a long-term adaptation to D2 antagonism at the level of gene expression which occurs over a similar time scale to that of the clinical response to neuroleptic treatment of schizophrenia.
Brain Res Mol Brain Res 1991 May
PMID:Stereospecific effect of flupenthixol on neuroreceptor gene expression. 164 66

The expression of various GABAA receptor subunit mRNAs (alpha 1, alpha 2, alpha 3, alpha 5, beta 1, beta 2, beta 3, gamma 2, delta) was studied in the adult rat lumbar spinal cord by in situ hybridization. Of these, only alpha 2, alpha 3, beta 3 and gamma 2 mRNAs are expressed at significant levels. The alpha 3, beta 3 and gamma 2 transcripts are present in many neurons throughout the Rexed laminae, whereas the alpha 2 mRNA is restricted to motor neurons and adjacent cells.
Brain Res Mol Brain Res 1991 May
PMID:Distribution of GABAA receptor subunit mRNAs in rat lumbar spinal cord. 164 70

The vertebrate mechanisms for generating circadian rhythms, regulating the synthesis of melatonin, and modulating the activities of pineal indole-synthesizing enzymes differ significantly among species. The synthesis of melatonin in mammalian pineal glands is stimulated by beta 1-adrenergic receptor agonists and is potentiated by alpha 1-adrenergic receptor agonists, whereas in the avian pineal gland alpha 2-adrenergic receptor agonists inhibit its synthesis. By using [3H]rauwolscine, a selective alpha 2-adrenergic receptor antagonist, we have identified for the first time alpha 2-adrenergic receptor sites in a mammalian pineal gland. [3H] Rauwolscine bound in a saturable manner to a single class of receptors, with an equilibrium dissociation constant (KD) of 1.4 nM and a density (Bmax) of 71 fmol/mg of protein, in crude synaptic membrane preparations from bovine pineal gland. Competition studies carried out with various adrenergic antagonists supported the conclusion that [3H]rauwolscine binding sites were alpha 2-adrenergic receptors. The bovine pineal alpha 2-adrenergic receptor appears to represent a pharmacological subtype distinct from the three currently proposed subtypes, i.e., alpha 2A found in a human colonic adenocarcinoma cell line (HT29 cell), alpha 2B found in rat lung, and alpha 2C found in an opossum kidney cell line (OK cell). However, the pharmacologic profile of the pineal alpha 2 receptor resembles that found in the rat submaxillary gland. We suggest that the bovine pineal receptor may represent a fourth pharmacological subtype, which would be designated as alpha 2D.
Mol Pharmacol 1991 Aug
PMID:Identification and characterization of alpha 2D-adrenergic receptors in bovine pineal gland. 165 52

The amyloid beta protein (ABP) has been shown to interact with the substance P (SP) receptor in a cell culture model that may mimic the pathogenesis of Alzheimer's disease. In the present study, however, 4 fragments of ABP (beta 1-42, beta 1-16, beta 17-28, and beta 25-35) failed to interact with SP-induced Ca2+ mobilization in SP receptor-expressing cultured cells. Therefore, the action of these ABP-related peptides in our cultured cells is unrelated to the SP receptor.
Brain Res Mol Brain Res 1991 Sep
PMID:Amyloid beta protein substituent peptides do not interact with the substance P receptor expressed in cultured cells. 166 16

A murine fibroblast cell line (AKR-2B clone 84A) and an epithelial cell line (BALB/MK) were compared for their ability to bind different transforming growth factor-beta (TGF beta) species. The results of competitive binding assays indicated that the epithelial cells had a higher affinity for TGF beta than the fibroblasts. This difference may be the basis for the sensitivity of epithelial cells to much lower concentrations of TGF beta than fibroblasts. Affinity cross-linking studies showed that both cell types express the three cell surface TGF beta-binding molecules that have been previously described for a variety of cell types. The complexity of these cell surface binding proteins was further evaluated using all possible combinations of radiolabeled ligands in competition with each of the three unlabeled TGF beta species. Differences in the ability of specific TGF beta types to compete with radiolabeled TGF beta 2 for binding to the type I and II receptors were observed, with TGF beta 1 being more potent for epithelial cells, and TGF beta 2 being more potent for fibroblasts. In addition, a difference in the ability of different TGF beta species to compete the [125I]TGF beta 3 from epithelial cell surface receptors was apparent. TGF beta 2 was not able to compete with [125I]TGF beta 3 for binding to the type II receptor at any concentration tested, while TGF beta 1 and TGF beta 3 were about equally potent in competition for this receptor type. These differences in cell surface receptor binding of structurally and biologically similar molecules may reflect different functions for these molecules.
Mol Endocrinol 1991 Dec
PMID:Differential binding of transforming growth factor-beta 1, -beta 2, and -beta 3 by fibroblasts and epithelial cells measured by affinity cross-linking of cell surface receptors. 166 3


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