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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of tumor-promoting phorbol diesters to potentiate the action of epidermal growth factor (EGF) on cell proliferation is associated with phosphorylation of EGF receptors, acute depression of EGF binding, and inhibition of EGF receptor tyrosine kinase activity. In the present studies, normal human fibroblasts and A431 carcinoma cells were labeled with [32P]phosphate and treated with and without 10 nM 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA). The EGF receptors then were isolated by immunoprecipitation and digested with trypsin. Analysis of the labeled receptor phosphopeptides by reversed-phase HPLC revealed that PMA induces the phosphorylation of a unique phosphopeptide containing [32P]phosphothreonine. Comparison of several chemical and physical properties of the 32P-labeled phosphopeptide with the primary structure of the EGF receptor suggested the identify Lys-Arg-Thr(P)-Leu-Arg. This was confirmed by direct demonstration that a synthetic peptide of this structure comigrates during HPLC and electrophoresis with the 32P-labeled phosphopeptide isolated from the EGF receptors of normal human fibroblasts. The phosphorylated site on the peptide corresponds to threonine-654 of the EGF receptor, which is located on the cytoplasmic side of the plasma membrane nine residues distant from the transmembrane domain. These data indicate that phosphorylation of the EGF receptor in human fibroblasts and A431 cells at threonine-654 may regulate the EGF receptor tyrosine kinase activity and the binding of EGF.
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PMID:Tumor-promoting phorbol diesters cause the phosphorylation of epidermal growth factor receptors in normal human fibroblasts at threonine-654. 298 76

The proliferation of 3T6 cells was substantially decreased when the monolayer cultures were allowed to reach confluency. This growth inhibition (so-called density-dependent inhibition) was of the same magnitude as that following serum depletion in non-confluent cultures. Each type of growth inhibition was correlated to a depression of the activity of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG CoA) reductase, an enzyme that regulates the biosynthesis of cholesterol and isoprenoid derivatives (e.g. dolichol) by catalysing the reduction of HMG CoA (which is derived from acetyl-CoA) into mevalonate. However, the depression of enzyme activity was more substantial in cells exposed to cell crowding than that in serum-depleted cells (87 and 48%, respectively). On the other hand, there was a 60-65% inhibition of the incorporation of mevalonate into dolichol due to serum deprivation, while it remained at normal level in confluent cultures, which implies that the inhibitory effects on dolichol synthesis due to these two experimental conditions were approximately equipotent. Addition of epidermal growth factor (EGF) to the cell cultures, whose proliferation was inhibited due to serum depletion, restored DNA synthesis completely, and these effects were related to a normalization of the activity of HMG CoA reductase and of the incorporation of mevalonate into dolichol. In contrast, in confluent cells addition of EGF only caused a slight increase in DNA synthesis and activity of HMG CoA reductase, and there was no significant increase in the incorporation of mevalonate into dolichol either.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The role of HMG CoA reductase and dolichol synthesis in the control of 3T6 cell proliferation: effects of cell crowding, serum depletion and addition of epidermal growth factor. 326 15

Observations on the effect of thyroid hormones on mouse submaxillary gland epidermal growth factor (EGF) and on the complementary effect of EGF on cultured thyroid cells led us to examine the interaction between EGF and thyroid hormones in the whole animal, during and after 24 h of infusion of 3.3 micrograms/kg X h mouse EGF into 6 merino ewes. There was a profound depression of both circulating T4 and T3 levels, to less than 20% of saline-infused control values, extending beyond the end of infusion. Plasma TSH concentrations were unchanged during the first 8 h of the infusion, excluding the likelihood of a suppressive effect of EGF on the hypothalamic-pituitary axis. Serum rT3 and 3,3'-diiodothyronine, however, experienced a more transitory 6-fold increase. These findings are consistent with a dual inhibitory effect of EGF on both thyroid hormone secretion and peripheral metabolism.
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PMID:Epidermal growth factor: effect on circulating thyroid hormone levels in sheep. 348 43

Increased protein tyrosyl phosphorylation in response to growth factors has been assumed to be solely due to activation of protein tyrosine kinases (PTKs). We report that total cellular protein tyrosine phosphatase (PTPase) activity declined in MDA-MB 468 breast carcinoma cells exposed to epidermal growth factor (EGF). The PTPase activity decreased with concentration as well as with time of EGF incubation. As EGF induces increases in intracellular Ca2+ concentrations and such changes may result in depression of PTPase activity, we treated cells with the calcium ionophore A 23187. Increases in calcium induced by the ionophore resulted in activation of cellular PTPases as indicated by increased dephosphorylation of tyrosine phosphorylated EGFR by cellular lysates. Thus, both the extracellular ligand EGF and the intracellular messenger Ca2+ were shown to modulate cellular PTPase activity in MDA-MB 468 breast carcinoma cells. However, EGF-induced decreases in PTPase activity cannot be attributed to EGF-induced increases in intracellular Ca2+ levels.
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PMID:Role of intracellular Ca2+ in the epidermal growth factor induced inhibition of protein tyrosine phosphatase activity in a breast cancer cell line. 768 60

Even though the first monoclonal antibodies (MAbs) directed against tumor cells were produced 15 yr ago, the therapeutic application of immunoconjugates is still at the beginning. This is principally because of the enormous work that is required for the development of completely new therapeutic tools. An alternative could be to only use MAbs to improve conventional treatment such as chemotherapy. To this aim, a MAb directed against doxorubicin (DXR) was produced. DXR is an anthracycline antibiotic of which the clinical usefulness in cancer chemotherapy is limited by serious side effects, such as cardiomyopathy, bone marrow depression, and gastrointestinal tract mucositis. This toxicity was found to be reduced by treatment with the antidrug MAb, as shown by reduction in body weight loss and mortality of experimental mice. To improve the DXR therapeutic index, a bifunctional hybrid MAb (DOXER2), capable of simultaneously recognizing DXR and the epidermal growth factor (EGF) receptor, was produced. This reagent was found in vitro to increase the drug toxicity on the epidermoid carcinoma cell line A431, which overexpresses the EGF-R and, at the same time, to reduce DXR cytotoxicity on EGF-R negative cells. The effect of DOXER2 on the DXR biodistribution in vivo was also investigated. In mice previously injected ip with the DOXER2, the uptake of the drug, in comparison to the control group, was found to be reduced in the intestine and in myocardial tissue, and significantly increased in the tumor.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of a bifunctional monoclonal antibody directed against a tumor marker and doxorubicin on the growth of epidermoid vulvar carcinoma grafted in athymic mice. 773 15

Interleukin-1 beta depresses the voltage-gated Ca2+ channel currents in acutely dissociated guinea-pig hippocampal CA1 neurons. This depression is observed with pathophysiological concentrations found in the cerebrospinal fluid (> or = 1.0 pg interluekin-1 beta/10 microliters). Interleukin-1 receptor antagonist (in concentrations 25-fold higher than interleukin-1 beta) completely blocked the interleukin-1 beta-induced depression of the Ca2+ channel current. This suggests that interleukin-1 beta action is through a specific interaction with an interleukin-1 membrane receptor site. The application of other cytokines and growth factors (interleukin-6, epidermal growth factor, and basic fibroblast growth factor), or bacterial lipopolysaccharide (endotoxin) had no effect, indicating specificity of action of interleukin-1 beta. The depression of the Ca2+ channel current by interleukin-1 beta was prevented by the extracellular application of pertussis toxin, and by the intracellular application of GDP[beta S], H-7, staurosporine or bisindolylmaleimide. Application of phorbol 12-myristate 13-acetate also depressed the Ca2+ channel current, but this phorbol ester-induced depression was not additive to that induced by interleukin-1 beta. These results suggest mediation of interleukin-1 beta action through a pertussis toxin-sensitive G-protein coupled interleukin-1 receptor associated with the activation of protein kinase C. The depression of the Ca2+ channel current by interleukin-1 beta may be involved in the regulation of neuronal excitability during pathological conditions and in the induction and/or progression of neurodegenerative processes.
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PMID:Interleukin-1 beta inhibits Ca2+ channel currents in hippocampal neurons through protein kinase C. 813 77

Hepatocytes isolated from male B6C3F1 mice and maintained in primary culture were exposed to epidermal growth factor (EGF), hepatocyte growth factor (HGF), acidic fibroblast growth factor (aFGF) alone or in combination with the mitoinhibitory transforming growth factor beta 1 (TGF-beta 1). Groups of mice were exposed to 3.5 g/l dichloroacetic acid (DCA), 0.1% phenobarbital (PB) or the drinking water vehicle for 0, 2, 5, 10, 20, 30, 60, or 90 days. Following a 2 h attachment period, the growth factors with or without TGF-beta 1 were added together with [3H]thymidine. The cells were harvested 48 h later and the incorporation of the labeled thymidine into cellular DNA was determined. Basal DNA synthesis was enhanced following 2 days of PB treatment after which it declined to levels significantly below that in the untreated mice. No early time enhancement of DNA synthesis was measured in the hepatocyte cultures for animals exposed to DCA, but the late time inhibition was also seen. Primary cultures of hepatocytes isolated from control and DCA treated mice exhibited similarly enhanced DNA synthesis in response to eGF, HGF, or aFGF alone or in combination with TGF-beta 1. In contrast, hepatocytes from PB treated animals were refractory to the effects of the growth factors at all time periods. These data suggest that the early depression of cell proliferation we have seen during DCA induced hepatocellular cancer is not due to an impaired ability of hepatocytes to respond to growth factors and that the mechanisms of liver tumorigenesis in the mouse induced by PB and DCA are dissimilar.
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PMID:Responsiveness of hepatocytes from dichloroacetic acid or phenobarbital treated mice to growth factors in primary culture. 861 22

It has been hypothesized that the physiological basis of follicle selection is the differential expression of factors, which modulate the action of gonadotrophins on follicular cells, at key points during the process of follicle development. The aim of this research was to test this hypothesis by identifying factors that can enhance or attenuate the action of the gonadotrophins in stimulating follicle development using both in vivo and in vitro models. Experiments in vivo utilized sheep with an ovarian autotransplant to allow intra-arterial infusion of putative local factors and exposure of the ovary to high local concentrations. Experiments in vitro utilized physiological serum-free cell culture systems for both granulosa and theca cells that allow gonadotrophin-induced differentiation in vitro. The putative local factors tested included insulin-like growth factor-I (IGF-I LR3 analogue), transforming growth factor alpha (TGF alpha) or epidermal growth factor (EGF) and inhibin A. IGF-I stimulated both cellular proliferation and hormone production by both granulosa and theca cells in vitro and similarly stimulated ovarian follicle development and ovarian androgen and oestradiol secretion in vivo. Both TGF alpha and EGF stimulated granulosa and thecal cell proliferation in vitro in a dose-responsive manner and concomitantly inhibited hormone production, whereas intra-arterial infusion of TGF alpha in vivo resulted in induction of atresia in large antral follicles and an acute fall in ovarian hormone secretion. Inhibin A in vitro augmented gonadotrophin stimulated androgen and oestradiol production by thecal and granulosa cells, respectively, but had no effect on cell number. Paradoxically, intra-arterial infusion of inhibin A resulted in an acute depression in ovarian steroid secretion. This depression, however, was also associated with an acute depression in circulating FSH concentrations. In conclusion, these data provide strong support for the hypothesis that factors can modulate the action of gonadotrophins on follicular cells to augment (IGF-I, inhibin A) or inhibit (TGF alpha/EGF) granulosa and thecal cell differentiation. The challenge for the future in this area of research is to understand how these factors interact to enable one follicle to be selected from an ovulatory cohort.
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PMID:The modulation of gonadotrophic hormone action on the ovary by paracrine and autocrine factors. 1048 30

Tricyclic antidepressants are still a dominating group of psychotherapeutic drugs used in the treatment of depression. Oral dryness is one of their major side-effects, leading in humans to increased oral disease and dysfunction of speech, chewing, swallowing and taste. We previously reported that the tricyclic antidepressant desipramine desensitizes beta-adrenergic signal transduction in salivary glands. In this study, we evaluated the effects of this treatment on parotid and submandibular gland function, oral microbiota, and oral health in rats. Total protein secretion and salivary alpha-amylase was not affected by treatment, while cellular alpha-amylase and the content of epidermal growth factor was depressed. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed increased secretion for proline-rich proteins and glycoproteins. Surprisingly, flow rates were temporarily increased. These alterations in salivary gland function may partially explain the observed changes in oral microbiota and the increased incidence of gingivitis. Under other nutritional conditions, desipramine might have more severe impacts on oral health.
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PMID:Desipramine changes salivary gland function, oral microbiota, and oral health in rats. 1107 Jan 87

Dry mouth is one of the major side effects of cyclic antidepressants, which are still a dominating group of psychotherapeutic drugs used in the treatment of depression. In this study we analyzed the effects of 28 day tricyclic antidepressant administration and the reversibility of this treatment following a 15 day washout period on different parameters in submandibular gland function in aging rats. We postulated that desipramine would decrease gland function, accented with age, and delay recovery in senescent animals. In contrast to body weight, desipramine had no effect on glandular wet weight. While glandular DNA synthesis was changed with age and treatment, the concentration of total membrane and soluble proteins was not affected. Flow rate was significantly changed with age, but desipramine increased salivary flow in the youngest animals only. Neither age nor treatment influenced salivary protein concentrations, but the total amount of proteins secreted, revealed perturbation with age. SDS- polyacrylamide gel analysis revealed changes in protein expression with treatment and age. Desipramine decreased epidermal growth factor (EGF) levels in all age groups, but increased the secretion of peroxidase and lysozyme. Analysis of total RNA showed a pronounced decrease with age. These data indicate that desipramine has profound effects on submandibular salivary gland function.
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PMID:An analysis of submandibular salivary gland function with desipramine and age in female NIA Fischer 344 rats. 1108 May 33


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