Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three transgenic mouse models which proved to develop endocrine tumours are reviewed and discussed. The neoplasms were induced through the production of the transforming oncoprotein simian virus 40 (SV40) large T-antigen. The SV40/metallothionein-growth hormone (MGH), the insulin/SV40 (INS/SV40) and the vasopressin/SV40 (AVP/SV40) transgenic mice models all developed endocrine tumours of pancreas mainly composed of insulin-producing B cells, with a minor PP cell component. In the pancreata of INS/SV40 and AVP/SV40 transgenic mice, non-tumour lesions (hyperplasia and dysplasia) were also described. AVP/SV40 transgenic mice presented tumour genesis in anterior pituitary too. The usefulness of transgenic mouse models in reproducing human pathology is outlined with special reference to genetically dependent tumours.
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PMID:Transgenic mouse models and peptide producing endocrine tumours: morpho-functional aspects. 252 89

Arginine vasopressin (AVP) is a potent neuroactive and vasoactive nonapeptide encoded in and processed from a precursor, preproarginine vasopressin-neuro-physin II (preproAVP-NPII). To study the physiologic consequences of a genetic model of chronic hypervasopressinemia transgenic mice were produced by introduction of a mouse metallothionein-rat-ppAVP-NPII fusion gene into the germ line of mice. Three stable transgenic pedigrees were analyzed through several generations. Levels of immunoreactive AVP and neurophysin (NP) in sera, livers, kidneys, intestines, pancreas, and brains were markedly elevated. Chromatographic analyses showed sera levels of approximately 500 pg/ml (normal 0-20 pg/ml) of authentic AVP non-apeptide and serum osmolalities were elevated, 315.4 +/- 1.4 mosm/liter (control, 307.3 +/- 1.1), consistent with a state of mild nephrogenic diabetes insipidus. Brain levels of immunoreactive AVP in transgenic mice were 3-4-fold elevated 145 +/- 15 ng/g versus 31 +/- 7 (controls). Although immunoreactive AVP in livers and intestines, and to some extent kidneys, consisted predominantly of unprocessed precursors, in brain and pancreas greater than 90% of AVP consisted of processed bioactive nonapeptide, as determined by chromatography and measurements of cAMP-generation in LLC-PK1 cells. Immunocytochemistry localized immunoreactive AVP to the exocrine pancreas and to the magnacellular neurons (SON and PVN) of the hypothalamus. Expression of the fusion gene in the hypothalamus was further demonstrated by Northern analyses of fusion gene specific transcripts and in situ histohybridization. Although the fusion gene contained only 35 base pairs of 5'-flanking DNA of the ppAVP-NPII gene, a tentative neuronal cell-specific expression element, -17GCCCAG-CC-10 resides in this sequence and may confer neuron-specific expression to the fusion gene.
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PMID:Metallothionein-vasopressin fusion gene expression in transgenic mice. Nephrogenic diabetes insipidus and brain transcripts localized to magnocellular neurons. 280 95

Preprovasopressin-neurophysin II (prepro-AVP-Np), the precursor of the cyclic, amidated nonapeptide, arginine vasopressin (AVP), is present in the central and peripheral nervous systems, adrenal glands, and gonads of rats. To study cell-specific processing of prepro-AVP-Np, a fusion gene consisting of the heavy metal-inducible promoter of the mouse metallothionein I gene and the rat prepro-AVP-Np gene was introduced by cellular transfection into several defined cell phenotypes: a fibroblast line (BHK), a pituitary growth hormone and prolactin-producing cell line (GH4), a pituitary cell line that produces several amidated peptides (AtT-20), and an insulin-producing pancreatic islet line (RIN- 1046-38). Clonal cell lines were isolated and prepro-AVP-Np-specific transcripts were detected by Northern blot hybridization analyses. Fibroblast BHK and pituitary GH4 cells transfected with the fusion gene synthesized a polypeptide (Mr = 18,000) characteristic of the glycosylated precursor, pro-AVP-Np; in metal -treated cells, this protein was the major secreted cysteine-labeled polypeptide. Extracts of RIN-1046-38 and AtT-20 cells transfected with the fusion gene contained predominantly processed neurophysin and amidated arginine vasopressin, whereas extracts of BHK and GH4 cells contained mainly precursors of AVP and neurophysin. These observations indicate that the pathways involving specific post-translational processing of pro-AVP-Np are more efficiently utilized in the prohormone-producing AtT-20 and RIN-1046-38 cells than in GH4 and BHK cells that do not synthesize any recognized prohormones.
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PMID:Provasopressin-neurophysin II processing is cell-specific in heterologous cell lines expressing a metallothionein-vasopressin fusion gene. 365 60

Adult rat primary hepatocytes maintained in DMEM/F12 (Ham) media were used as a model system for studying the role of fetal calf serum (FCS) and agonists of the phosphoinositide cascade in the metabolism of metallothionein (MT) and alkaline phosphatase (ALP). Experiments were performed both after a 24 h preincubation with FCS and with bovine serum albumin (BSA). Hepatocytes were treated with dexamethasone (DEX), zinc (Zn) and with the agonists of the phosphoinositide cascade A23187, 1,2-dioctanoyl-sn-glycerol (DiC8), 12-O-tetradecanoylphorbol-13-acetate (TPA), angiotensin II (AT), platelet activating factor (PAF), Arg8-vasopressin (VP) and were analyzed for MT and ALP activity in cell homogenates. Cell viability was evaluated by lactate dehydrogenase (LDH) liberation into culture medium, induction of tyrosine aminotransferase (TAT) through DEX and by trypan blue exclusion. Overall, cell viability was improved by the FCS pretreatment and by DEX. Exposure of hepatocytes to the established direct inducers Zn and DEX of MT resulted in a manifold increase in MT, independent of whether the cultures were FCS pretreated or not. The FCS preincubation produced a moderate elevation of ALP activity by stimulating cell viability. However, ALP was unaltered in response to Zn and DEX. None of the experiments conducted with agonists of the phosphoinositide cascade led to an elevation of MT and ALP. Only the incubation of hepatocytes with A23187 resulted in a concentration dependent significant decrease of MT and ALP. This observation was due to a cytotoxic effect of A 23187, displayed by LDH leakage and an increase in the number of cells stained with trypan blue. In conclusion, in primary hepatocyte cultures agonists of the phosphoinositide did not have an effect on the metabolism of MT and ALP. Previous in vivo results indicating alterations of Zn metabolism in liver, therefore seem to be caused by indirect systemic responses.
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PMID:Studies on the metabolism of metallothionein and alkaline phosphatase of adult rat primary hepatocyte cultures: role of fetal calf serum and agonists of the phosphoinositide cascade. 823 77

Several metal ions are known to cause depolymerization of the actin cytoskeleton under some circumstances. We found that in renal mesangial and vascular smooth muscle cells, micromolar concentrations of Cd2+ result in loss of phalloidinstainable filamentous (F-) actin. The decrease in F-actin was not accompanied by a corresponding increase in G-actin. The decrease in total actin could be accounted for in part by an inhibition by Cd2+ of total protein (and actin) synthesis after 6 to 8 h without an effect on actin degradation, and the equilibrium between F- and G-actin was shifted to maintain near-constant levels of G-actin. However, Cd2+ caused significant decreases in F-actin at earlier times, indicating effects on the polymerization equilibrium independent of those on actin synthesis. Only picomolar concentrations of free intracellular Cd2+ occur in these experiments. However, it is this Cd2+ pool which is responsible for F-actin depolymerization because equal cellular concentrations of cadmium delivered as Cd-metallothionein have no effect. The effect is also very specific for Cd2+ and under the same conditions neither Mg2+, Mn2+, Co2+, Ni2+, Cu2+, Zn2+, nor Hg2+ result in any loss of F-actin. Addition of Cd2+ to mesangial and vascular smooth muscle cells had no immediate effect on free intracellular calcium concentrations ([Ca2+]i) even though Ca(2+)-signalling pathways were intact as shown with vasopressin and endothelin. Exposure to 10 microM CdCl2 for 8 h nevertheless caused an increase in [Ca2+]i to > 250 nM and increases in [Ca2+]i achieved with ionophores alone were sufficient to decrease F-actin concentrations. However, a rise in [Ca2+]i is not necessary for actin depolymerization. Depletion of cellular Ca2+ by treatment with thapsigargin did not protect F-actin against Cd2+; the effect of Cd2+ was enhanced in cells unable to increase their [Ca2+]i. We conclude that depolymerization of F-actin by Cd2+ in smooth muscle and mesangial cells is metal-specific, Ca(2+)-independent, and accompanied by a depletion of total actin protein.
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PMID:Calcium-independent effects of cadmium on actin assembly in mesangial and vascular smooth muscle cells. 867 40

We analyzed an X-linked metallothionein-vasopressin (MTVP) fusion transgene that undergoes X-chromosome inactivation (X inactivation) and an X-linked transferrin (TFN) transgene that escapes X inactivation with respect to methylation in the 5' regulatory regions. The MTVP transgene promoter region is unmethylated when the transgene is on the active X chromosome and methylated when on the inactive X chromosome. Interestingly, the MTVP transgene is not detectably transcribed from the male X chromosome, although it is unmethylated, consistent with its availability for transcription. The TFN transgene promoter region is hypomethylated on both the active and inactive X chromosomes, consistent with its expression from both chromosomes. The TFN and MTVP transgenes have been mapped to chromosomal regions D and C, respectively, by fluorescence in situ hybridization. These observations are discussed in the context of our understanding of the role of DNA methylation in the spread and maintenance of X-chromosome inactivation.
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PMID:Comparative methylation analysis of murine transgenes that undergo or escape X-chromosome inactivation. 987 69

Arginine vasopressin (AVP) is a major antidiuretic hormone, the overproduction of which causes diluting hyponatremia in humans and is called the syndrome of inappropriate antidiuresis (SIAD). To study physiological changes resulting from AVP overproduction and to develop an animal model of hyponatremia, the human AVP gene was expressed under the control of the metallothionein promoter in transgenic (Tg) rats. Analyses of AVP immunoreactivity (irAVP) in the tissues revealed that the transgene is expressed mainly in the central nervous system. Gel filtration showed that irAVP in the brain and plasma was properly processed AVP. AVP purified from the brains of both Tg and control rats also exerted equal bioactivity to generate cAMP in LLC-PK1 cells. The founder rats did not show any physical or anatomical abnormalities. Under basal conditions, Tg rats had high plasma AVP levels (Tg 13.8 +/- 2.5 pg/ml; control 2.7 +/- 1.2 pg/ml; n=6 in both groups; means +/- S.E.M.), decreased urine volume, and normal plasma [Na(+)]. Hypertonic saline injected i.p. did not affect AVP secretion in Tg rats. In response to a zinc-supplemented liquid diet, plasma AVP decreased in control rats, but increased in Tg rats (Tg 32.7 +/- 2.7 pg/ml; control 1.0+/-0.1 pg/ml; n=6), resulting in hyponatremia (Tg 135.2 +/- 2.5 mEq/l; control 140.8 +/- 0.4 mEq/l; n=6). To our knowledge, this is the first transgenic animal to show diluting hyponatremia. This transgenic rat may therefore provide a useful model in which to investigate various physiological alterations resulting from the oversecretion of AVP which involve SIAD, stress response, behavior, and blood pressure.
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PMID:Overexpression of vasopressin in the rat transgenic for the metallothionein-vasopressin fusion gene. 1192 82

Magnocellular neurons (MCNs) in the hypothalamo-neurohypophysial system synthesize high levels of the peptides oxytocin (OT) and vasopressin (VP) in separate cells. We used RT-PCR amplification of the RNA from single-cells dissected from supraoptic nuclei of lactating rats to produce cDNAs from identified OT or VP MCNs, which were used to construct OT- and VP-MCN-specific cDNA libraries. These cDNA libraries were then screened using labeled probes from the OT- and VP-cells' amplified cDNAs. Differentially hybridized colonies were isolated and characterized by slot blot hybridization, Southern blot hybridization, DNA sequencing, and in situ hybridization histochemistry. Using this approach, several novel cell-specific mRNAs were identified in the MCNs. One cell-specific clone, phosphofructokinase-C, was isolated from the OT-cell library, and five cell-specific clones were isolated from the VP-cell library. These were identified as paternally expressed gene (Peg)5/neuronatin, metallothionein III, Peg3, synaptotagmin V, and a 3'-phosphoadenosine 5'-phosphosulfate synthase 2-related mRNA. None of these genes would have been predicted to be differentially expressed in OT and VP MCNs, based on our current knowledge; and hence, this single cell differential gene expression approach has begun to further define the MCN phenotypes by identifying selectively expressed molecules in them.
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PMID:Identification of cell-specific messenger ribonucleic acids in oxytocinergic and vasopressinergic magnocellular neurons in rat supraoptic nucleus by single-cell differential hybridization. 1239 44