Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.10.3.1 (tyrosinase)
 9,065 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The s.c. administration of gamma-L-glutaminyl-4-hydroxybenzene (GHB) to neonatal black mice produced a prompt, generalized, and selective swelling and lysis of the melanocytes of the hair follicles. The findings indicate that this cytotoxic effect was dependent upon the intracellular activation of GHB by tyrosinase. Supportive of this conclusion were: (a) an absence of comparable cytological alterations in adjacent keratinocytes; (b) a lack of response by melanocytes of albino mice; and (c) patterns of deficient pigmentation produced by GHB in juvenile black mice, suggesting that susceptible follicles were those in the tyrosinase-producing growth phase. The administration of GHB also induced condensation, or "apoptosis," of individual follicular keratinocytes of both black and albino mice and in the melanocytes in the latter. This response was apparently independent of tyrosinase. It was transitory and without appreciable effect on hair growth. The findings further characterize the selective cytolytic properties of GHB for mammalian cells that possess tyrosinase and suggest a potential for this natural compound as a chemotherapeutic agent against melanocarcinoma.
Cancer Res 1979 May
PMID:The cytotoxicity of gamma-L-glutaminyl-4-hydroxybenzene for cells that contain tyrosinase, a study of melanocytes in the hair follicle of the mouse. 10 60

Serum tyrosinase activity in many persons with metastatic diseases was found to be significantly higher than activity in normal persons. The highest activity was observed in melanoma and breast carcinoma. The electrophoretic patterns of serum tyrosinase, resolved by electrophoresis of a serum tyrosinase fraction followed by incubation of the gel sample with L-dopa, and represented as sets of RF's of melanin bands, were characteristically different in melanoma, breast carcinoma, and certain other diseases. The RF's of melanin and protein bands in the serum enzyme preparations from melanoma patients were concisely defined. Further, some potent serum fractions inhibiting tyrosinase melanogenic activity have been obtained, and the presence of tyrosinase inhibitors in the serum enzyme preparation has also been demonstrated. More detailed exploration of these serum tyrosinase parameters may provide more specific and sensitive detection for certain malignant diseases.
Cancer Res 1979 Sep
PMID:Serum tyrosinase in malignant disease, its activity, and the electrophoretic patterns of the enzyme as carried by immunoglobulins'. 11 92

The tyrosinase activity in two sucrose gradient isolated melanosome fractions from a melanotic hamster melanoma was found to increase after alpha-chymotrypsin treatment. The enhancement in tyrosinase activity had its maximum at a concentration of 1 mg/ml alpha-chymotrypsin after 120 min incubation at 37 degrees C. No direct activating effect of alpha-chymotrypsin was found either on the soluble tyrosinase fraction from freshly prepared untreaed whole-tumor homogenate or on purified mushroom tyrosinase. The activating effect of alpha-chymotrypsin upon the melanosome tyrosinase is believed to be due to the endopeptidic hydrolysis of the--CO--NH--bound existing between tyrosinase and tyrosine and phenylalanine residues in the melanin molecule. Although alternative interpretations are not excluded, the observed enhancement in tyrosinase activity after alpha-chymotrypsin treatment of melanosomes might indicate the existence of an "enzyme liberating" mechanism in the melanosomes.
J Cancer Res Clin Oncol 1979 Oct
PMID:Chymotrypsin activation of melanosome tyrosinase in hamster melanotic melanoma. 11 73

A human melanoma cell line established in our laboratory was characterized in terms of tyrosinase activity and anionic polysaccharide production. Tyrosinase levels were diluted during the growth phase and increased after the cell culture became confluent. The anionic polysaccharides produced included hyaluronic acid, heparitin sulfate, and a high-molecular-weight condroitin 4-sulfate. In contrast, a primary culture of human melanocytes derived from embryonic iris produced much greater amounts of hyaluronic acid, about 30-fold less heparitin sulfate, and a mixture of chondroitin 4-sulfate and dermatan sulfate. Saccharides secreted into the culture medium were generally identical to those remaining cell associated except for the melanoma heparitin sulfate, wherein the latter fraction appeared to be of lower molecular weight.
Cancer Res 1976 Feb
PMID:Anionic polysaccharide production and tyrosinase activation in cultured human melanoma cells. 13 Sep 71

In the genetically determined pigment cell tumors of platyfish and platyfish-swordtail hybrids, the degree of malignancy of pigment cells which have been neoplastically transformed by a tumor gene (Tu) depends on the type and number of certain regulating genes (R). In the present study, the tyrosinase activities in tumors of different degrees of malignancy (black spots, premelanomas, melanomas) have been determined. The results demonstrate a close correlation between the level of tyrosinase activity and the degree of malignancy. Spot patterns consisting of completely differentiated (benign) Tu-transformed cells show no tyrosinase activity. Premelanomas containing a few incompletely differentiated (malignant) Tu-transformed cells in addition to many differentiated ones show moderate tyrosinase activities. Melanomas which contain increasing numbers of incompletely differentiated cells with increasing growth rates show high to extremely high tyrosinase activities. Thus, the tyrosinase levels present in these tumors can be used as an indicator for the degree of differentiation and, thereby, for the degree of malignancy of the neoplastically transformed pigment cells.
Z Krebsforsch Klin Onkol Cancer Res Clin Oncol 1977 Dec 15
PMID:Melanogenesis in genetically determined pigment cell tumors of platyfish and platyfish-swordtail hybrids: correlation between tyrosine activity and degree of malignancy. 14 30

1. Titration of Neurospora tyrosinase with 2-mercaptoethanol shows that the increase of absorbance at 700 nm is directly correlated to the loss of enzymatic activity. Approximately 2 mol of 2-mercaptoethanol per mole of protein are needed for full development of the green, enzymatically inactive complex. The increase of absorbance at 700 nm is also proportional to the intensity of the EPR signal and the amount of non-covalently bound 2-[35S] mercaptoethanol to the enzyme. The maximal EPR intensity reaches 70% of the protein concentration and at most 0.7--0.8 mol of 2-[35S] mercaptoethanol is bound per mol of enzyme. 2. Stopped-flow measurements show that in the reaction between 2-mercaptoethanol and Neurospora tyrosinase a raction intermediate with a strong absorption band at 360 nm is formed in an apparent second-order reaction. This intermediate displays no EPR-detectable signals. The intermediate decays in a similar complex fashion as the absorption band at 700 nm is formed. 3. The reaction of Neurospora tyrosinase with a variety of sulfhydryl compounds was also investigated. In most cases green coloured, enzymatically inactive complexes are formed displaying slightly different EPR signals. However, with cysteine and cysteamine violet coloured, enzymatically inactive complexes are formed which show rather different EPR signals. The integrated EPR intensities amount to 40--70% of the protein concentration. Based on simulations of 9 and 35 GHz spectra all observed EPR spectra can be represented as true S = 1/2 systems. The cysteamine complex can be interpreted as arising from a mixed valence Cu2+ . Cu+ complex. The 2-mercaptoethanol spectra can, however, arise from sulphur radicals. 4. Treatment of Agaricus bispora tyrosinase and Cancer pagures hemocyanin with 2-mercaptoethanol results in green-coloured, EPR detectable complexes similar to the one found with Neurospora tyrosinase. No such complexes are formed when hemocyanins from Helix pomatia and Panulirus interruptus were treated with this reagent.
 ...
PMID:The reaction of mercaptans with tyrosinases and hemocyanins. 20 26

The control of melanin production, tyrosinase activity, and cell replication by melanocyte-stimulating hormone (MSH) and cyclic AMP (cAMP) was examined in differentially metastasizing B16 mouse melanoma variants. In B16-F1 cells (low metastatic potential), MSH or cAMP greatly elevated tyrosinase activity and melanin content while inhibiting cell replication. The same parameters in B16-F5 cells (intermediate metastatic potential) were altered to a much lesser degree, whereas B16-F10 cells (high metastatic potential) were not significantly affected by MSH or cAMP. Therefore, a correlation exists between loss of hormonal regulation and increased metastatic potential.
J Natl Cancer Inst 1978 Aug
PMID:Control of melanogenesis in mouse melanoma cells of varying metastatic potential. 21 Feb 94

A stable phenol, gamma-L-glutaminyl-4-hydroxybenzene (GHB), is oxidized by tyrosinase in the gill tissues of the mushroom Agaricus bisporus to a quinone and a second oxidation product which together suppress mitochondrial energy production and the synthesis of proteins and nucleic acids in the zygote, thus establishing dormancy in the spores. Brief incubation of cultured murine L1210 leukemia and B-16 melanoma cells with muM concentrations of the purified quinone notably prolonged survival times or blocked tumor growth in histocompatible mice inoculated i.p. with high concentrations of the exposed cells. The instability of the quinone precluded in vivo administration. The short incubation of cultured B-16 melanoma cells with mM concentrations of GHB markedly prolonged survival times or abolished tumor growth in histocompatible C57BL/6J mice inoculated i.p. with 5 X 10(6) exposed cells. This response did not occur with L1210 leukemia cells, which lack the enzyme tyrosinase. The survival times of mice bearing B-16 melanoma, but not of those with L1210 leukemia, were slightly prolonged by a single injection and were significantly extended by daily i.p. injections of GHB. Normal C57BL/6J mice, given GHB i.p. as single or multiple 400-mg/kg doses, manifested no systemic toxicity but showed depigmentation of the hair after 2 to 3 weeks. These studies provide evidence that GHB exerts cytotoxicity specifically for cells that by their content of tyrosinase convert the phenol to the quinone. This targeted response minimizes systemic toxocity and underscores the potential therapeutic application of this agent to melanocarcinoma.
Cancer Res 1977 Apr
PMID:gamma-L-Glutaminyl-4-hydroxybenzene, an inducer of cryptobiosis in Agaricus bisporus and a source of specific metabolic inhibitors for melanogenic cells. 40

Serum tyrosinase activity has been measured by adapting the [3]tyrosine assay for tyrosinase and significant elevations of serum tyrosinase activity were found in patients with malignant melanoma. In contrast to findings in a study which utilized [14C]tyrosine, augmented levels of tyrosinase activity were not observed in sera from patients with other malignancies, including subjects with carcinoma of the breast. The results of the examinations for soluble tyrosinase activity in human malignant melanoma tissue-cultured lines were all positive, whereas human cell lines from carcinoma of the breast, carcinoma of the colon and sarcoma uniformly showed no activity. The method employed for detecting tyrosinase activity holds promise as a specific diagnostic test and may be valuable for monitoring the response to clinical treatment of patients with malignant melanoma.
Int J Cancer 1977 Nov 15
PMID:Tyrosinase activity in the sera of patients with malignant melanoma: method and specificity. 41 60

A number of biochemical aspects of melanogenesis were studied in 15 variously melanized human melanomas. The tryosinase activity was correlated with the degree of melanoma varied from 3,667 to 46,183 tryosinase units, in partially melanotic melanoma it varied from 14 to 75 tryrosinase units. The subcellular distribution of tryrosinase activity was limited to the particulate fraction )144,000 x g) of the partially melanotic and amelanotic melanomas. However, the melanotic melanomas contained the enzyme in both particulate and soluble fractions, with the greater tyrosinase activity in the particulate fraction. Electrophoretic resolution of tyrosinase isozymes in the soluble fraction or lipase-solubilized tyrosinase derived from the particulate fraction revealed three isozymes in melanotic melanomas. The isozyme of intermediate mobility always was the dominant form. In partially melaotic melanomas, the solubilized tyrosinase showed six isozymes. Three were similar to those of melanotic melanomas. The remaining three isozymes showed slower mobilities, possibly with greater molecular weights than the isozymes derived from melanotic melanomas. Inhibitors of tyrosinase were present in melanomas. Increased tyrosinase activity occurred after storing the homogenate at 0-4degree, removing of supernatant from the homogenate sediment, and washing the 144,000 x g particulate fraction, which suggested the presence of water-soluble, loosely bound inhibitor (s) in the soluble fraction of partially melanotic melanoma. Another inhibitor was released from the 144,000 x g particulate fraction of melanotic melanoma after lipase digestion. These substances inhibit both the isolated dominant tyrosinase isozyme(human) and mushroom tyrosinase. As inhibition of tyrosinase activity may produce regression of abnormal cell growth, the inhibitors may provide an approach to melanoma chemotherapy.
Cancer Res 1975 Mar
PMID:Melanogenesis in human melanomas. 80 70


1 2 3 4 5 6 7 8 9 10 Next >>