Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The lag in cresolase activity and inhibition by excess tyrosine of mushroom tyrosinase which was observed when assayed at pH 6.8 was found to be absent when assayed at pH 5.0. The absence of lag and inhibition by excess tyrosine of tyrosinase at pH 5.0 were brought about only after the enzyme was kept at pH 5.0, at 0-4 degrees C, for 1.5 h. The enzyme kept at pH 5.0 for 1.5-3 h at 0-4 degrees C when brought back to pH 6.8, acquires lag and inhibition by excess tyrosine when its activity was measured at pH 6.8. The pH-dependent changes in the kinetic properties of the mushroom tyrosinase are similar to the pH-dependent changes in the kinetic properties of tyrosinase from B-16 murine melanoma and human skin, and thus appear to be a general property of tyrosinase from diverse sources.
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PMID:pH-dependent interconvertible forms of mushroom tyrosinase with different kinetic properties. 249 46

In cultured cells of the Bomirski Ab amelanotic hamster melanoma line, the substrates of tyrosinase, L-tyrosine, and L-DOPA induce the melanogenic pathway. In this report, we demonstrate that these substrates regulate the subcellular apparatus involved in their own metabolism and that this regulation is under the dynamic control of one of the components of this apparatus, tyrosinase, via tyrosine hydroxylase activity. Culturing cells with nontoxic but melanogenically inhibitory levels of phenylthiourea (PTU; 100 microM) strongly inhibits induction of both the tyrosine hydroxylase and DOPA oxidase activities of tyrosinase by L-tyrosine (200 microM) but has no effect on the induction of either activity by L-DOPA (50 microM). De novo synthesis of premelanosomes precedes the onset of tyrosine-induced melanogenesis. Thereafter, increases in the population of melanosomes (likewise inhibited by PTU) correlate positively with increases in tyrosinase activity induced by L-tyrosine. Melanogenesis induced by L-DOPA in the absence of L-tyrosine is rate-limited not by tyrosinase but by inadequate melanosome synthesis. Our findings indicate that in Bomirski Ab amelanotic hamster melanoma cells the synthesis of the subcellular apparatus of melanogenesis is initiated by L-tyrosine and is regulated further by tyrosinase and L-DOPA, which serves as a second messenger subsequent to tyrosine hydroxylase activity.
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PMID:L-tyrosine, L-dopa, and tyrosinase as positive regulators of the subcellular apparatus of melanogenesis in Bomirski Ab amelanotic melanoma cells. 249 48

Citrate stimulates cresolase activity of tyrosinase from B-16 murine melanoma and human skin. Maximal stimulation by citrate was obtained at 2 mM, and stimulation was decreased at higher concentrations. Citrate stimulates tyrosinase not only from mammalian sources but also from mushroom. The stimulation was not due to reversal of inhibition of enzyme activity by excess tyrosine. On rapid decrease in pH of the enzyme solution from 6.8 to 5.0-5.2, the enzyme is no longer inhibited by excess tyrosine even when its activity was assayed at pH 6.8. Citrate also stimulates this form of enzyme. However, the stimulation is more at acidic pH than at pH 6.8. At higher concentrations of citrate the stimulatory effect decreases at both pH 5.0 and pH 6.8. Inhibition of this enzyme occurs at higher concentrations (22 mM) at pH 6.8. The physiological role of stimulation of cresolase activity of tyrosinase by citrate is yet to be unravelled.
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PMID:Citrate activates tyrosinase from B-16 murine melanoma and human skin. 249 49

Pyrularia thionin, isolated from nuts of Pyrularia pubera, is a strongly basic peptide of 47 amino acids. The amino acid sequence and configuration of its four disulfide bonds place this plant peptide, known to be hemolytic, cytotoxic, and neurotoxic, among the thionins. We report and compare several cellular responses mediated by Pyrularia thionin: hemolysis of human erythrocytes, activation of an endogenous phospholipase A2 in Swiss 3T3 cells, cytotoxicity toward HeLa and mouse B16 melanoma cells in culture, viability of rat hepatocytes and lymphocytes measured by trypan blue exclusion, and lethality in mice. Cellular responses related to ion movement include a toxin-mediated influx of Ca2+ into mouse P388 cells measured by Fura-2 fluorescence, depolarization of mouse P388 plasma membrane measured by fluorescence of bis(1,3-diethylthiobarbituric acid)trimethine oxonol (bisoxonol), and depolarization of frog (Rana pipiens) sartorius muscle determined by direct measurement of membrane potential. Graded iodination of Pyrularia thionin leads to a related loss of activity for hemolysis, phospholipase A2 activation, cytotoxicity, and lethality in mice. The mediated Ca2+ influx into and depolarization of P388 cells require Ca2+ in the external medium and are inhibited by 100 microM Ni2+. Depolarization of sartorius muscle by Pyrularia thionin also requires a functional Ca2+ channel, as shown by verapamil inhibition. This muscle depolarization also involves phospholipase A2 activation because dexamethasone and quinacrin, but not indomethacin, protect against depolarization. The IC50 values for viability of rat hepatocytes and splenic lymphocytes measured by trypan blue exclusion were 0.17 and 40 microM, respectively. The general response of cells to Pyrularia thionin involves a membrane alteration leading to depolarization and a channel-mediated influx of Ca2+. There is a related activation of phospholipase A2 that results in loss of membrane integrity, hemolysis in the case of erythrocytes, and eventually cell death. Iodination of Pyrularia thionin leads to a corresponding inhibition of all three cellular responses, which indicates an essential role for tyrosine in either maintenance of peptide structure or interaction of the peptide with cellular membranes.
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PMID:Cellular responses to Pyrularia thionin are mediated by Ca2+ influx and phospholipase A2 activation and are inhibited by thionin tyrosine iodination. 250 25

This study sought to determine whether human melanoma cells express integrin-related receptors that mediate their adhesion to laminin. We found that antibodies against the integrin beta 1 chain blocked cell attachment to laminin-coated surfaces. Furthermore, immunofluorescence staining demonstrated beta 1 complexes in vinculin-positive focal adhesion plaques on the basal surface of cells attached to laminin substrates. Chromatography of detergent extracts of 125I-surface-labeled cells on laminin-Sepharose columns recovered two major laminin-binding proteins (100 and 130 kDa, reduced) that bound with high affinity to the columns and were eluted with EDTA. Both proteins were specifically immunoprecipitated from column fractions with monoclonal and polyclonal antibodies to the integrin beta 1 subunit, indicating that they form a noncovalent heterodimer complex. The alpha-like subunit is composed of a 30-kDa light chain that is joined by a disulfide bond to the 100-kDa heavy chain. This complex was not recovered from columns of fibronectin- or collagen type I- or IV-Sepharose. Laminin-binding by the alpha beta 1 complex was independent of Arg-Gly-Asp or Tyr-Ile-Gly-Ser-Arg-like sequences, but required the presence of divalent cations. The 100-kDa alpha-like subunit was electrophoretically and immunochemically distinct from the other known alpha subunits, alpha 1-alpha 6. The results indicate that human melanoma cells express a novel laminin-specific integrin beta 1 complex which may mediate the cells' interactions with this ligand.
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PMID:Human melanoma cells express a novel integrin receptor for laminin. 252 55

The specific binding of an alpha MSH analogue (Ac-[Nle4, D-Phe7] alpha MSH4-11 NH2) was enhanced in the presence of 10% dialyzed fetal calf serum (FCS) as compared with 10% FCS (nondialyzed) in the F1 variant of B16 melanoma cells. The replenishment of dialyzed serum with adrenocorticotrophic hormone (ACTH) or insulin had no effect on the increased level of alpha MSH receptor binding in these cells. However, 10 nM alpha MSH or 1 microM ACTH under identical conditions significantly decreased the level of alpha MSH binding. Competitive binding studies involving the alpha MSH analogue revealed that the specificity of the receptor was restricted to the complete molecule of alpha MSH, our analogue, beta MSH and ACTH1-24, ACTH4-10, which contains the amino acid sequence responsible for biological activity, showed a very low affinity for the receptor. Furthermore, we observed an interesting phenomenon unique to dialyzed FCS in that once the cells were grown to confluence and melanin was produced, the cells were no longer viable. However, in McCoy's medium, which is deficient in tyrosine, the cells did not produce melanin and remained viable.
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PMID:Evidence for increased alpha MSH receptor binding in the F1 variant of B16 melanoma cells grown in dialyzed fetal calf serum. 255 51

In Bomirski Ab amelanotic hamster melanoma cells, L-tyrosine and/or L-dopa induce increases in tyrosinase activity as well as synthesis of melanosomes and melanin. L-tyrosine also modifies melanocyte-stimulating hormone (MSH) binding. In this paper we show that in the Bomirski amelanotic melanoma system MSH and agents that raise intracellular cyclic AMP induce dendrite formation, inhibit cell growth, and cause substantial increases in tyrosinase activity without inducing melanin synthesis. Tyrosinase activity is detected only in broken cell preparations, or cytochemically in fixed cells. In the continued absence of mature melanosomes, the induced enzyme remains in elements of the trans-Golgi reticulum. Comparative measurements of cyclic AMP in amelanotic and tyrosine-induced melanotic cells show similar basal levels. L-tyrosine and L-dopa have little or no effect, whereas MSH may cause a 1000% peak increase in cyclic AMP levels both in amelanotic and melanotic cells. None of these agents influences cyclic GMP or inositol trisphosphate (InsP3) levels. In agreement with the InsP3 assays, phorbol ester (TPA) has no effect on melanization, tyrosinase activity or cell proliferation. In conclusion, in the Bomirski amelanotic melanoma, MSH induces only partial cell differentiation associated with raised levels of cyclic AMP. Induction of melanosome synthesis and melanization by L-tyrosine or L-dopa appear to follow pathways unrelated to cyclic AMP, cyclic GMP or InsP3.
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PMID:MSH inhibits growth in a line of amelanotic hamster melanoma cells and induces increases in cyclic AMP levels and tyrosinase activity without inducing melanogenesis. 255 57

Two analogues of alpha-MSH (Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2), Ac-[Nle4, Asp5, D-Phe7, Lys10]alpha-MSH4-10NH2 and Ac-[Nle4, Asp5, D-Phe7, Lys10] alpha-MSH4-10-NH2, were synthesized, and the melanotropic activities of the peptides were compared in several bioassays. Potencies were determined in the in vitro frog and lizard skin bioassays and in the S91 melanoma cell tyrosinase assay. Both analogues were equipotent or more potent than alpha-MSH in all bioassays, and the activities of the analogues were prolonged compared to alpha-MSH. The two analogues were very resistant to inactivation by purified proteolytic enzymes (alpha-chymotrypsin, trypsin, and pepsin). The two peptides could be topically applied and transdermally delivered across the skin of mice in vivo, resulting in a shift from pheomelanogenesis to eumelanogenesis within follicular melanocytes. The cyclic analogue exhibited greater potency, prolonged activity, and stability against enzyme inactivation than did the linear peptide. The significance of the findings for the further design of melanotropin analogues is discussed, as in the possible relevance of these melanotropin analogues for use in biomedical studies.
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PMID:Linear and cyclic alpha-melanotropin [4-10]-fragment analogues that exhibit superpotency and residual activity. 255 3

The biosynthesis of melanin from tyrosine is reviewed as the basis for assessment of laboratory tests that might potentially aid in the diagnosis and management of patients with malignant melanoma. These tests include qualitative and quantitative assays for the intermediates in metabolism of melanin and catecholamines, enzyme assays, metal ion analyses, and, most recently, immunoassays. Although currently no role exists for the clinical laboratory in the early diagnosis of malignant melanoma, serial quantitative analyses of total or individual melanogens or of catecholamine metabolites in urine or plasma specimens may be of value in the management of patients with this disorder. Immunologically based methods for the diagnosis and management of malignant melanoma hold some promise for the future.
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PMID:Role of the clinical laboratory in the diagnosis and management of malignant melanoma. 267 22

The insulin receptor contains in its beta-subunit a tyrosine (-) specific protein kinase. It is believed that transmission of an insulin signal across the plasma membrane of target cells of insulin action occurs through activation of this kinase, autophosphorylation of the insulin receptor beta-subunit and subsequent phosphorylation of other cellular substrates. We studied the insulin receptor kinase in a number of insulin resistant cell systems in order to elucidate if defects of this kinase are a possible cause of cellular insulin resistance. Three different patterns of kinase abnormalities were found, in different insulin resistant cells: 1. In an insulin resistance melanoma cell line a reduced receptor kinase autophosphorylation was found apparently due to a defect of the tyrosine autophosphorylation sites of this receptor; 2. Catecholamine and phorbol ester induced insulin resistance of isolated rat fat cells as well as human fat cells was associated with a decreased activity of the insulin receptor tyrosine kinase which was apparently due to a modulation of the ATP binding site of the insulin receptor tyrosine kinase; 3. The receptor kinase isolated from the skeletal muscle of diabetic Zucker rats (fa/fa) was found to be insulin insensitive with no major alteration of maximal responsiveness. These results suggested that different forms of kinase defects exist which can contribute to the pathogenesis of cellular insulin resistance. Based on these data studies in skeletal muscle from type II diabetic patients were started. Results from five patients so far suggest that, here as well, an abnormality of the insulin receptor kinase exists which might be involved in the pathogenesis of insulin resistance in type II diabetes.
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PMID:Insulin receptor kinase defects as a possible cause of cellular insulin resistance. 282 Aug 11


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