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

Total amounts and turnover rates of phosphoinositides and inositol phosphates in normal rat liver and hepatocyte nodules were investigated. Male Wistar rats were injected i.p. with [3H]inositol 18-20 h before killing. The amount of phosphatidylinositol in a homogenate preparation was roughly doubled in the nodules, though levels of polyphosphoinositides were approximately the same. Basal levels of inositol phosphates were the same in nodules and in normal liver. Turnover rates of inositol tris- and tetrakisphosphates were studied after stimulation of intact cells with vasopressin for different periods of time (0-5 min). The initial rate of formation of inositol trisphosphate after agonist exposure was fast in both nodular and normal cells. Nodular cells reached peak amount of inositol trisphosphate at 2.5-fold basal levels after 20 s, while normal cells peaked after 40 s at 4.5 times the basal amount. The level of inositol tetrakisphosphate was enhanced very quickly in normal cells, but in the nodular cells there was no increase of this inositol phosphate after vasopressin stimulation. To investigate the mechanism of this difference, the activities of inositol 1,4,5-trisphosphate kinase and of inositol 1,4,5-trisphosphate phosphatase were studied. Both activities were rapid and equal in nodules and normal liver. The amount of cell surface receptors for vasopressin was shown to be one-third in the nodules, as compared to normal cells. This quantitative decrease in receptor number was reflected in lower formation of inositol trisphosphate when stimulated with vasopressin, but could not explain the loss of inositol tetrakisphosphate response in nodules. The significance of the reported alterations in second messenger traffic for the growth regulation of nodular cells and for their progression to carcinoma is not yet known, but could add to the nodules being less dependent on growth regulating signals.
Carcinogenesis 1992 Aug
PMID:Inositol phosphates and phosphoinositides in rat liver nodules. 132 28

A quantitative in vitro transformation assay has been developed for the first time using primary rat kidney epithelial (RKE) cells. RKE cells were grown in a 50:50 mixture of 3T3 conditioned medium and DF8 medium composed of Ham's F-12/DMEM supplemented with ferrous sulfate, vasopressin, transferrin, sodium selenite and 10% fetal bovine serum. Colony forming efficiency of cells plated in this medium was high, ranging from 2.4 to 16%. Normal RKE cells treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) became transformed to a preneoplastic state of enhanced in vitro growth potential and formed large colonies of morphologically altered cells, whereas RKE cells treated with vehicle alone ceased proliferating and/or sloughed off the dish within 4-6 weeks. Relative survival and percent transformation frequency (Tf) of RKE cells exposed to MNNG were inversely proportional and both were dose dependent. MNNG concentration of 0.5, 1.0 and 2.0 micrograms/ml resulted in transformation frequencies of 0.13, 0.37 and 1.1% respectively (n = 4). Morphologically transformed colonies gave rise to cell lines with indefinite growth capacity and neoplastic potential. One of six transformed RKE cell (TRKE) lines injected into nude mice produced adenocarcinomas. This assay represents the first in vitro model for studying mechanisms of chemical transformation of normal kidney epithelial cells and may also be useful as a screen for identifying potential renal carcinogens.
Carcinogenesis 1992 Jan
PMID:Development of a quantitative in vitro transformation assay for kidney epithelial cells. 173 69

A culture system is described in which rat kidney proximal tubule epithelial cells (RPTE) can be prepared with good yield and high viability and grown in culture under serum-free conditions. The cells require EGF, insulin, cholera toxin and either 1% dialyzed serum or a complex of bovine serum albumin with oleic acid (BSA/OA). The cells can be maintained for long periods of time and express several markers for RPTE. The cells have both alkaline phosphatase and gamma-glutamyltransferase activity and respond to parathyroid hormone but not vasopressin. The specific activity of gamma-glutamyltransferase decreases when the cells begin to grow, but increases when they reach confluence. Extracellular calcium plays a role in the induction of gamma-glutamyltransferase in confluent cells. Cells grown in media containing low calcium, i.e. less than 0.4 mM, have reduced specific activity of gamma-glutamyltransferase. Extracellular calcium also alters the morphology of the cells in that cells grown in low calcium are single cells or loose clusters suggesting poor cell-cell contact. When the calcium is raised to 1.0 mM, the cells change their shape and organization to adopt the morphology of cells maintained continuously in 1.0 mM calcium. The cells can be passaged onto plastic surfaces which have been coated with collagen but cannot be subcultured on uncoated or serum coated plastic. This culture system will be a useful model for the investigation of renal carcinogenesis and the role of cell proliferation in that process.
 ...
PMID:Rat kidney proximal tubule cells in defined medium: the roles of cholera toxin, extracellular calcium and serum in cell growth and expression of gamma-glutamyltransferase. 256 95

Ornithine decarboxylase activity of rat lung was induced by s.c. injection of acetylcholine, norepinephrine, epinephrine, dopamine, serotonin, vasopressin, angiotensin II, and adrenocorticotropic hormone, but not by gonadotropin, aldosterone, corticosterone or hydrocortisone. The possible significance of hormonal factors in lung carcinogenesis is discussed, based on the reported promoting activity of vasopressin in cultured cells.
 ...
PMID:Induction of ornithine decarboxylase activity in rat lung by neurotransmitters and peptide hormones. 289 98

In our studies of normal and neoplastic growth regulation, we have compared growth factor induced second messenger response and mitogenic activity in a rat hepatocarcinogenesis model. Inositol phosphate (IP) turnover was measured by incubating the cells with [3H]inositol and stimulating them with either epidermal growth factor, diferric transferrin, ferricyanide, vasopressin, norepinephrine, angiotensin II or bombesin for 2 min. The IPs formed were separated on HPLC. Mitogenic responses were monitored by bromodeoxyuridine uptake and labeling index. IP turnover was stimulated by vasopressin, norepinephrine and angiotensin II in both normal and nodular cells, but not by the other four agonists tested. The IP response was somewhat lower in cells from liver nodules. All compounds except bombesin were mitogenic to both nodular cells and cells from normal rats of different ages, with epidermal growth factor inducing the largest mitogenic response. Bombesin, on the other hand, had only a minor effect on normal cells, but induced a pronounced mitogenic response in nodular cells. In normal rats, the cells' ability to respond to growth stimulation decreased with increasing rat age. In this respect, nodular cells behaved in a way more like young normal cells than their age-matched controls. Taken together, these data support the view of liver nodules being a more autonomous cell population, with increased sensitivity to growth factors and possibilities for autocrine growth stimulation.
Carcinogenesis 1994 Sep
PMID:Growth factor induced mitogenic effects and inositol phosphate responses in primary hepatocyte cultures from normal rat liver and rat liver nodules. 792 74

Mutations in DNA underlie carcinogenesis, inherited pathology, and aging and are generally thought to be introduced during meiosis and mitosis. Here we report that in post-mitotic neurons specific frameshift mutations occur at high frequency. These mutations were identified in vasopressin transcripts in magnocellular neurons of the homozygous Brattleboro rat and predominantly consist of a GA deletion in GAGAG motifs. Immunocytochemistry provides evidence for similar events in wild-type rats. However, the diseased state of the Brattleboro rat, resulting in a permanent activation of vasopressin neurons, enhanced the mutational rate. These data reveal hitherto unrecognized somatic mutations in nondividing neurons.
 ...
PMID:Frameshift mutations at two hotspots in vasopressin transcripts in post-mitotic neurons. 801 15

We detected low level expression of the gastrin-releasing peptide and neuromedin-B receptor mRNAs in cultures of human bronchial epithelium from 4 of 6 individuals. Bombesin receptor subtype-3 mRNA was undetectable in these cells. An elevation of intracellular calcium concentration was observed in response to bradykinin (6 of 6) and neurotensin (1 of 5) but not to bombesin (0 of 6), vasopressin (0 of 6), or cholecystokinin (0 of 3). In contrast, such responses are frequently noted in lung cancer cell lines. Bombesin did not stimulate the in vitro growth of an immortalized human bronchial epithelium cell line expressing low levels of bombesin receptor mRNAs. We conclude that bombesin receptors are expressed at low levels in human bronchial epithelium cells which may acquire greater responsiveness to multiple neuropeptides in the course of multistep carcinogenesis.
 ...
PMID:Receptor subtype expression and responsiveness to bombesin in cultured human bronchial epithelial cells. 813 67

Adult rat hepatocytes, after maintenance for 24 h in serum-free culture, were treated with the tumor promoters, 12-O-tetradecanoylphorbol-13-acetate (TPA) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Short-term treatment (15 min) with TPA, 1 microM, increased protein kinase C (PKC) activity in the particulate fraction of hepatocytes and, concomitantly, decreased the vasopressin (100 nM)-stimulated synthesis of inositol phosphates. The latter effect of TPA could be prevented by prior addition of the PKC inhibitor, H7 (100 microM). After short-term treatment (15 min) with TCDD, 1 pM, no effects on PKC or inositol phosphate metabolism were observed. However, after prolonged exposure to TCDD (3-48 h), the particulate PKC was significantly activated (1.5-fold). In contrast to the effect of TPA (24 h), no down-regulation was found. Moreover, long-term treatment with TCDD significantly enhanced vasopressin-stimulated inositol 1,3,4,5-tetrakisphosphate synthesis, while TPA treatment (24 h) stimulated the synthesis of inositol trisphosphates and inositol 1,3,4,5-tetrakisphosphate. The results suggest that the tumor promoters, TPA and TCDD, act differently on the signal transduction pathways in hepatocytes. Thus, the effects of TCDD on PKC and inositol phosphate metabolism might be mediated by a yet unknown mechanism rather than by direct activation of PKC as seen with TPA.
Carcinogenesis 1993 Nov
PMID:Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on protein kinase C and inositol phosphate metabolism in primary cultures of rat hepatocytes. 824 56

Tyrosine kinase receptor HER2/neu plays an important role in a number of processes including carcinogenesis. The oncogenic characteristics of HER2/neu are associated with its ability to affect a variety of apoptotic pathways creating, this way, an antiapoptotic environment in the cells overexpressing this protein. The aim of our work was to investigate the features of apoptosis regulation in hypothalamic neurosecretory cells of HER2/neu transgenic mice in aging. We detected the apoptosis protein expression (Bax, c-Raf) in comparison with apoptosis level and functional activity (vasopressin concentration) in neuroendocrine system. Besides, we studied the level of 17beta-estradiol in blood plasma. 17beta-estradiol is one of possible antiapoptotic factors in neurons. We show that the apoptosis of neuroendocrine cells increases in aged wild type mice, but not in HER2/neu ones. Recently we obtained that the mechanism of apoptosis suppression in transgenic mice is the block of p53-dependent apoptosis cascade, and it is the cause of caspadse-8 decrease and dysregulation of Bcl-2 and Mcl-1 antiapoptotic protein synthesis. In this study it has been shown that Bax concentration decreases and c-Raf-1 expression does not change. 17beta-estradiol does not decrease in plasma of aged transgenic mice and it is the factor, which can play a positive role in neuroendocrine cells survival. Besides, the vasopressin synthesis increases in young and old HER2 mice. These facts result in the increased survival of neurosecretory cells in old transgenic mice.
 ...
PMID:[Apoptosis regulation in hypothalamic neurosecretory cells of HER2/neu transgenic mice in ontogenesis]. 1838 7

Tumor necrosis factor (TNF) participates in regulation of many processes including carcinogenesis and apoptosis. However, at present, there are practically absent the works on peculiarities of regulation of apoptosis in tnf-knockout (tnf-/-) mice. These mice develop without morphological abnormalities, but they seem to have disturbances of many biological processes, such as inflammation, programmed cell death, etc. Therefore, the goal of our work was to study possible pathways of regulation of apoptosis in the absence of TNF in neurosecretory cells (NSC) of young and old mice. For this purpose, we determined immunohistochemically expression of apoptosis markers caspase-8, -9. Bax, Bcl2, Mcl1, neuropeptide vasopressin, and the apoptosis level in hypothalamus in tnf-knockout mice of different ages as compared with mice with unchanged level of TNF synthesis. It was shown that the apoptosis activation observed during aging did not depend on the tnf gene, and apoptosis at aging was caspase-dependent. It has been revealed that at aging in mouse NSC the external cell death pathway with participation of caspase-8 is activated. The pathways mediating cell death in different neurosecretory centers at aging are different. Thus, in supraoptic nucleus (SON), in all studied animal groups, animal groups, an important cause of the NSC apoptosis is Bax. In paraventricular nucleus (PVN), of the greater importance is a decrease of the antiapoptotic protection. Hence, misbalance of synthesis of proteins of the Bcl-2 family plays an important role in development of senescent apoptosis.
 ...
PMID:[Ontogenetic peculiarities of regulation of apoptosis in hypothalamic neurosecretory cells in thf-knockout mice]. 1988


1 2 Next >>