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 melanogenic activity of tyrosinase as a function of temperature was studied in 9 different skin and melanoma tissues of vertebrates. The 600 times g supernatant fraction of tissue homogenates was incubated with 14C-L-tyrosine at 0 degrees to 60 degrees C for 16 hr and the 14C-melanin product was determined. The range of optimal temperature occurred at 35 degrees to 45 degrees C. The maximal activity and thermostability depended on the source of the enzyme preparation utilized. Thermal activation and species differences in the optimal temperature for maximal activity are complicated processes which depend upon many factors. At cold conditions, a higher percentage of maximal activity was achieved with enzyme from cold-blooded species than with enzyme from warm-blooded species.
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PMID:Thermal activation and inactivation of melanin formation in vertebrate skins and melanomas. 80 28

D,L-tryptophan[benzene ring-14C (U)] and D,L-tryptophan (methylene-14C) are incorporated significantly into melanin of Harding-Passey mouse melanoma. D,L-5-hydroxytryptophan (methylene-14C) and 5-hydroxytryptamine-3-14C (serotonin) gave an incorporation of radioactivity into melanin significantly lower than tryptophan. D,L-tyrosine-2-14C was incorporated into melanin as well as tryptophan. Therefore tryptophan must be considered an important precursor in the biogenesis of melanins too.
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PMID:Studies on melanogenesis of tryptophan in Harding-Passey mouse melanoma. 124 96

Pigmentation of RVH 421 human melanoma cells is induced when cell division is inhibited by cytochalasin D or L-tyrosine phosphate. Increased pigmentation correlates with increased tyrosinase activity when this is monitored over a time-course. Parallel measurements show that the amount of tyrosinase mRNA correlates with enzyme activity in cells growing without these additives. In contrast, in the presence of cytochalasin D or L-tyrosine phosphate, the increase in amount of tyrosinase mRNA is not sufficient to account for the increase in enzyme activity, indicating that these compounds act mainly at a post-transcriptional level.
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PMID:Induction of tyrosinase in human melanoma cells by L-tyrosine phosphate and cytochalasin D. 137 60

L-DOPA, the product of enzymatic hydroxylation of L-tyrosine, is released by melanotic melanoma cells in vivo and in vitro. Here we report that DOPA at pharmacologically relevant micromolar doses dramatically inhibits the stimulation of DNA synthesis by lipopolysaccharide and concanavalin A in murine splenocytes and human lymphocytes, having little or no effect on unstimulated (control) lymphocytes or proliferating fibroblasts. Therefore we propose that melanogenically active melanoma cells can inhibit the host's immune response via the release of DOPA and/or its oxidation products.
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PMID:Dopa inhibits induced proliferative activity of murine and human lymphocytes. 162 34

Human tyrosinase (5.5 mg) has been purified from a single human melanotic melanoma metastasis (50.5 g). In the presence of dioxygen, L-tyrosine proved to be a very poor substrate for this enzyme with barely detectable activity compared to L-dopa. However, saturating superoxide anion (i.e., greater than 5 x 10(-3) M) enhanced the oxidation rate of L-tyrosine to dopachrome 40-fold. Hydrogen peroxide was shown to be a competitive inhibitor of tyrosinase when L-tyrosine was the substrate. This reversible inhibition is based on a slow pseudocatalase activity for tyrosinase. Monothiols and dithiols inhibit tyrosinase by different mechanisms. Reduced human thioredoxin and 2,3-dithiopropanol are allosteric inhibitors of tyrosinase yielding bis-cysteinate complexes with one of the copper atoms in the enzyme active site. Bis-cysteinate tyrosinase activity is down-regulated to 30% of native enzyme activity in the L-dopa assay; suggesting a true regulatory role for dithiols. Monothiols such as reduced glutathione and beta-mercaptoethanol are much less reactive with tyrosinase although 10(-3) M monothiol totally inhibits enzyme activity. Reduced thioredoxin inhibits tyrosinase 23-fold more than reduced glutathione under the same experimental conditions.
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PMID:Studies on the reactions between human tyrosinase, superoxide anion, hydrogen peroxide and thiols. 165 10

The stimulation of melanogenesis by L-tyrosine in hamster melanoma is several-fold higher than that by norepinephrine, epinephrine, clonidine and isoproterenol and absent in the case of tyramine dopamine and phenylephrine. Therefore, the melanogenic effect of L-tyrosine in hamster melanoma follows a different pathway than that linked to the activation of dopaminergic and adrenergic receptors.
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PMID:On the putative mechanism of induction and regulation of melanogenesis by L-tyrosine. 167 26

The effect of a number of L-tyrosine (L-Tyr) analogues on L-Tyr uptake by B16/F10 malignant melanocytes is reported. This amino acid can be taken up by two of the most ubiquitous transport systems found in animals cells, L and presumably ASC. L-Tyr analogues devoid of the amino group, like p-hydroxyphenyl pyruvic acid and related compounds, and L-Tyr analogues devoid of the carboxyl group, such as tyramine, do not affect L-Tyr uptake. The other aromatic amino acids, L-Phe and L-Trp, and the L-Tyr analogues DL-m-Tyr, L-diiodotyrosine and L-dopa, strongly inhibit the uptake of L-Tyr. This suggests that these chemicals are transported more efficiently than L-Tyr. The ASC system does not show stereospecificity, but the L system has greater affinity for L-Tyr than for D-Tyr. The ASC system also has greater affinity for tyrosine isomers with the hydroxyl group in the ortho and meta positions. The presence of a methyl group at the alpha-carbon of L-Tyr and L-dopa also increases the affinity of the ASC system for these agents. In contrast, alpha-methylation decreases the affinity of the L system in comparison to L-Tyr. Finally, L-Tyr esters do not inhibit, but stimulate the transport of L-Tyr, mainly by the ASC system.
Melanoma Res
PMID:Inhibition by analogues of L-tyrosine transport by B16/F10 melanoma cells. 182 66

Exposure of hamster amelanotic melanoma cells to L-tyrosine caused a time-dependent increase of tyrosinase protein concentrations, tyrosinase activity and level of cell pigmentation. In contrast, Northern blot analysis using mouse tyrosinase cDNA showed a steady level of tyrosinase mRNA. Thus in hamster melanoma cells the stimulation of intracellular tyrosinase concentration by L-tyrosine is mediated mainly via a posttranscriptional mechanism.
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PMID:L-tyrosine induces tyrosinase expression via a posttranscriptional mechanism. 190 10

Crosslinking of [14C]L-tyrosine to at least five hamster melanoma cell surface proteins is reported. This effect was abolished by addition of nonradioactive L-tyrosine, L-phenylalanine, or L-dopa, but not by D-tyrosine, tyramine, dopamine, norepinephrine, or epinephrine. The above proteins can be purified by tyrosine-affinity chromatography. They have molecular weights different from proteins staining for dopa oxidase and proteins that bind anti-tyrosinase antibody in Western blots. It is suggested that they may be a hithergo unrecognized part of the cellular apparatus governing melanogenesis.
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PMID:L-tyrosine-binding proteins on melanoma cells. 191 93

Melanocyte-stimulating hormone (MSH) induces melanogenesis in Cloudman mouse melanoma cells. The activities of two enzymes in the melanogenesis pathway, tyrosinase and dopachrome conversion factor, are increased as part of the induction process. Trans retinoic acid (RA), at concentrations as low as 0.1 nM, inhibited the induction of tyrosinase, dopachrome conversion factor, and melanogenesis, but had no effect on the basal levels of either enzyme or of cellular melanin content. Half-maximal effects of RA occurred at a concentration of 10 nM; maximal effects were observed at 1 microM. The effects of RA on melanogenesis were independent of its effects on cellular growth since one Cloudman line tested was growth-inhibited by RA and another was growth-stimulated by RA, but the induction of melanogenesis by MSH in both lines was inhibited by RA. Mixing experiments with cell lysates failed to demonstrate the induction of a tyrosinase inhibitor by RA. The effects of RA were not limited to MSH or to Cloudman melanoma cells since RA blocked cholera toxin-inducible melanogenesis in Cloudman cells, as well as the induction of tyrosinase activity by L-tyrosine in Bomirski hamster melanoma cells. The effects of RA were specific to melanogenesis, however, since RA did not interfere with MSH-induced changes in cellular morphology and growth. Thus, RA appears to be a new and potent tool for understanding mechanisms regulating induction of the pigmentary system.
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PMID:Retinoic acid is a potent inhibitor of inducible pigmentation in murine and hamster melanoma cell lines. 210 63


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