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)

New tyrosinase-targeted compounds based on structural variants of the prototype unit 4-aminophenol have been synthesized and screened for their potential as antitumour agents against malignant melanoma. Cytotoxicity assays showed that N-4-hydroxyphenylglycine (NHPG) and its alpha-methyl derivatives methylphenylglycine and dimethylphenylglycine exhibit significant antiproliferative effects on pigmented human melanoma cell lines (HBL), with inhibitory concentrations at 50% (IC50) around 80 micrograms/ml. A marked increase in cytotoxicity was observed with morpholine-containing 4-aminophenols, e.g. N-(2-morpholinoethyl)-4-aminophenol, which showed an IC50 of 20 micrograms/ml of HBL cells. Much more pronounced was the effect of the diacetoxy-derivative, DiAcMoAc, which showed an IC50 of 15 micrograms/ml on HBL cells and as low as 2 micrograms/ml on tyrosinase-containing, non-pigmented human melanoma cells (LND1), with a toxicity response of the same order of magnitude as that of melphalan. These results open interesting perspectives in the design of new targeted pro-drugs against malignant melanoma.
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PMID:Synthesis and cytotoxic properties of new N-substituted 4-aminophenol derivatives with a potential as antimelanoma agents. 164 21

The aim of the present work was to estimate the effect of intracellular glutathione depletion on melanogenesis in human melanoma cells. We determined tyrosine hydroxylation activity, the rate-limiting step of the pathway, and 14C-melanin formation, an assay reflecting the global eumelanogenic pathway. Intracellular glutathione was depleted by treatment with buthionine-S-sulfoximine, a well-known inhibitor of gamma-glutamylcysteine synthetase. The intracellular depletion of glutathione was substantial after 20 h of incubation with 50 microM buthionine-S-sulfoximine, although a significant effect could be observed after 6 h. Tyrosine hydroxylase activity increased in parallel with glutathione depletion, to reach 160% with respect to the control values during 24 h of buthionine-S-sulfoximine treatment. We have found the response to buthionine-S-sulfoximine to be dose dependent and the two different human cell lines HBL and LND1 to have similar, if not identical, responses. 14C-melanin formation assay revealed even greater activation, up to 400% of the control values. This indicates that glutathione depletion may have two distinct effects: first, a direct one on tyrosinase activity and, second, an effect on the promotion of eumelanogenesis. The stimulation of tyrosine hydroxylase can be explained by a possible inactivation of the enzyme by endogenous thiol compounds rather than by a direct effect of buthionine-S-sulfoximine itself on tyrosinase. The data suggest that thiol compounds may play a role for stimulation of melanogenesis by ultraviolet radiation.
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PMID:Glutathione depletion increases tyrosinase activity in human melanoma cells. 790 81

Most of our knowledge of the mammalian tyrosinase related protein (TRP) activities is derived from studies using murine melanoma models, such as B16 or Cloudman S-91 melanocytes. Owing to the high degree of homology between the murine and human enzymes, it has been assumed that their kinetic behaviour could be similar. However, the protein sequences at the metal binding sites of the murine and human enzymes show some differences of possible functional relevance. These differences are more significant in the metal-A site than in the metal-B site. By using three human melanoma cell lines (HBL, SCL, and BEU), we have studied the catalytic abilities of the human melanogenic enzymes in comparison to those obtained for the counterpart murine enzymes isolated from B16 melanoma. We have found that TRP2 extracted from all cell lines show dopachrome tautomerase activity, although the activity levels in human malignant melanocytes are much lower than in mouse cells. Reconstitution experiments of the human enzyme indicate that TRP2 has Zn at its metal binding-sites. Although mouse tyrosinase does not show DHICA oxidase activity, and this step of the melanogenesis pathway is specifically catalyzed by mouse TRP1, the human enzyme seems to recognize carboxylated indoles. Thus, human tyrosinase could display some residual DHICA oxidase activity, and the function of human TRP1 could differ from that of the murine protein. Attempts to clarify the nature of the metal cofactor in TRP1 were unsuccessful. The enzyme contains mostly Fe and Cu, but the reconstitution of the enzymatic activity from the apoprotein with these ions was not possible.
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PMID:Comparison of TRPs from murine and human malignant melanocytes. 926 30

The present paper deals with the effects of two active forms of brassinosteroids (BRs) as epibrassinosteroid (24-EBL) and homobrassinosteroid (28-HBL) on percentage germination, growth in the form of shoot length, activities of auxinase (IAAO), polyphenol oxidase (PPO), superoxide dismutase (SOD), catalase (CAT) and ascorbate peroxidase (APOX) in 10 day old seedlings of Brassica juncea L. (RCM 619) under field conditions. Exogenous application of 240-EBL and 28-HBL significantly ameliorate the total protein content as compared to untreated control seedlings. 10(-8) M 28-HBL helps in enhancing the PPO activity very significantly, as compared to all other concentrations of EBL and HBL and also to that of untreated control. Similar trend was observed in IAAO activity. It was observed that all the concentrations of EBL were unable to enhance the APOX activity as compared to untreated control seedlings but 10(-8) M HBL significantly ameliorates APOX activity. CAT and SOD activities ameliorate significantly with exogenous application of EBL and HBL. Out of two active forms of BRs, 28-HBL was more effective at germination stage in scavenging the free radicals, which are produced in greater amount during germination from basic metabolic processes, whereas 28-EBL was effective in the initial growth of seedlings in the form of increase in shoot length.
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PMID:Effects of 24-epibrassinolide and 28-homobrassinolide on the growth and antioxidant enzyme activities in the seedlings of Brassica juncea L. 2357 44