Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Cysteinyldopa”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 235 records · Page 13Linked to original sources
PubMedDate not supplied

Establishment and characterization of human vaginal malignant melanoma xenotransplants.

Human vaginal malignant melanoma represents rare gynecological malignancies of poor prognosis. We have established a melanoma tumor line in nude mice, designated Mela-1, and have examined the histological and biological characteristics of this tumor. The Mela-1 tumor has preserved the histological, histochemical and biological characteristics of malignant melanoma even after 20 passages. Tumor cells are of epitheloid shape varying in size. An ultrastructural study revealed that the tumor cells were characterized by the presence of cells with deeply indented nuclei, and both types of melanosomes, eumelanosomes and pheomelanosomes, in various stages of maturation with vesiculo-globular bodies in the cytoplasm. Melanin analysis of the tumor indicated the Mela-1 tumor to be pheomelanic. Immunohistochemical examinations revealed that the Mela-1 cells were stained positively by melanoma-associated antibody (NKI/C3) and by antibodies for S-100 protein and vimentin, and negatively for keratin and CEA. The levels of AFP, CA125 and CEA in sera of tumor-bearing mice were within normal range. The 5-S-cysteinyldopa level in sera of tumor-bearing mice correlated well with the size of the tumor. Chromosomal analysis showed the human karyotype with great heterogeneity and a modal number of 102 chromosomes. Thus the Mela-1 tumor will be useful in establishing the biological characteristics in the search for an effective treatment of human malignant melanoma of the vagina.

Animals↗
PubMed1978

Trichochromes in red human hair.

The presence of trichochromes B and C in red human hair was confirmed with an analytical procedure which does not give rise to the formation of these compounds as artifacts. The trichochrome precursor 5-S-cysteinyldopa previously demonstrated in red guinea-pig hair was not detected in red human hair.

Adolescent↗
PubMed1996

[Amines and pteridines].

Polyamines (putrescine, spermidine and spermine) play important roles in cell proliferation and differentiation, and have been established as tumors markers. We and other workers have confirmed that N1-acetylspermidine in tumor tissues, spermidine and spermine in erythrocytes, and N1,N12-diacetylspermine in urine might be the most sensitive indicators for various forms of tumors. Neopterin is a marker of cell-mediated immunostimulation, and may be a helpful marker in monitoring cancer patients. HPLC and immunological assays of neopterin, biopterin, and N2-(3-aminopropyl)biopterin(oncopterin) in urine might be useful in the clinical study of pteridines, as cancer markers. Serum 5-S-cysteinyldopa level is a useful and specific biochemical marker for malignant melanoma.

Biomarkers, Tumor↗
PubMed1977

Column cation-exchange separation of melanin-related metabolites in urine from cases of melanoma.

We describe recent developments in the use of a stable free radical, diphenylpicrylhydrazyl, as a colorimetric detector of reducing metabolites in melanoma urines. A procedure for buffering aqueous/solvent reagent solutions is presented, and examples of the baseline stability achieved for reference chromatograms and urine samples are provided. Chromatograms of phaeomelanin precursors and of an extract of a highly pigmented hamster melanoma are also presented. Identities are tentatively assigned for some of the chromatographic peaks that have previously been correlated with disease, including isomers of cysteinyldopa, and observations of new pigment- and tumor-related metabolites in the chromatograms are noted.

Animals↗
PubMed1997

Glutathione efflux associated with a low gamma-glutamyl transpeptidase activity in human melanoma cells.

The cellular concentration of reduced glutathione (GSH) modulates the sensitivity of human melanoma cells to alkylating drugs in vitro. To investigate whether the membrane-associated enzyme gamma-glutamyl transpeptidase (gamma-GTP) involved in GSH breakdown was expressed in melanoma cells, the enzymatic activity of gamma-GTP as well as the secretion of GSH were measured in human melanoma cells from four different cell lines (Me8, JUSO, GLL19, Swift). All the cells showed low gamma-GTP activities (0-1 mU/mg protein) and released GSH in culture supernatants at significant rates. After incubation for 24 h in growth medium containing 0.1 mmol/L cystine, the levels of GSH in supernatants ranged from 56 to 111 nmol GSH/mg protein. The GSH metabolism of melanoma cells was also evaluated by measuring the levels of the melanogenesis intermediate 5-S-cysteinyldopa under different experimental conditions. The results of these experiments suggest that melanoma cells have a low ability to metabolize the tripeptide GSH, which appears to be responsible for GSH secretion and accumulation in culture supernatants.

Cell Division↗
PubMed1976

Ultrastruct and biochemical chantes in cultured human malignant melanoma cells after heterotransplantation into nude mice.

Cells from three lines of cultured human malignant melanomas were heterotransplanted into nude mice and then recultered. The shape of the cells, the aspect of the melanosomes, and the content of 5-S-cyteinyldopa showed pronounced changes induced by the transplantation. Such results indicate that this experimental model should be used with great caution. A relationship was found between the shape of the melanosomes and the content of 5-S-cysteinyldopa in the cells.

Animals↗
PubMed2002

Stimulation of the proliferation and differentiation of mouse pink-eyed dilution epidermal melanocytes by excess tyrosine in serum-free primary culture.

The epidermal cell suspensions of the neonatal dorsal skin derived from wild type mouse at the pink-eyed dilution (p) locus (black, C57BL/10JHir-P/P) and their congenic mutant mouse (pink-eyed dilution, C57BL/10JHir-p/p) were cultured with a serum-free melanocyte growth medium supplemented with additional L-tyrosine (Tyr) from initiation of the primary culture. L-Tyr inhibited the proliferation of P/Pmelanocytes in a dose-dependent manner, whereas L-Tyr stimulated the proliferation of p/p melanoblasts and melanocytes regardless of dose. On the other hand, L-Tyr stimulated (P/P) or induced (p/p) the differentiation of epidermal melanocytes in a dose-dependent manner. In both P/P and p/p melanoblasts and melanocytes cultured with 2.0 mM L-Tyr for 14 days, slight increases in contents of eumelanin marker, pyrrole-2,3,5-tricarboxylic acid (PTCA) and pheomelanin marker, aminohydroxyphenylalanine (AHP) were observed. The average number of total melanosomes (stages I, II, III, and IV) per P/P melanocyte was not changed by L-Tyr treatment, but the proportion of stage IV melanosomes in the total melanosomes was increased. On the contrary, in p/p melanoblasts and melanocytes L-Tyr increased dramatically the number of stage II, III, and IV melanosomes as well as the proportion of stage III melanosomes. Contents of PTCA and eumelanin precursor, 5,6-dihydroxyindole-2-carboxylic acid (DHICA) of cultured media in p/p melanocytes were much more greatly increased than in P/P melanocytes. However, contents of AHP and pheomelanin precursor, 5-S-cysteinyldopa (5-S-CD) of cultured media in p/p melanocytes were increased in a similar tendency to P/Pmelanocytes. These results suggest that p/p melanocytes in the primary culture are induced to synthesize eumelanin by excess L-Tyr, but difficult to accumulate them in melanosomes.

Animals↗
PubMed2001

Quantification of melanoma-associated molecules in plasma/serum of melanoma patients.

Tumor markers for metastatic melanoma have, so far, been infrequently used. Although there is good evidence from several studies that protein S-100B serum measurement could serve as a valid marker for micro- and/or macrometastasis, the S-100B-LIAmat test has not been established as part of national and international recommendations for the care of melanoma patients. Future studies should focus on early detection of metastatic disease with S-100B compared to routine clinical, laboratory and technical evaluations. Furthermore, preliminary, interesting results on the predictive value of S-100B for the monitoring of metastatic patients during treatment should be verified in multicenter trials. The same considerations are true for melanoma-inhibitory activity (MIA), a new and interesting tool for the detection of metastatic melanoma. However, available data on the clinical use of on the MIA-ELISA are too limited to speculate on an even higher sensitivity and specificity than reported for S-100B. Melanin metabolites are candidates for valid melanoma markers, too. Quantification of 5-S-cysteinyldopa from blood or urine of melanoma patients has not been transferred from the laboratory to daily routine due to several technical problems in the assessment of this particular molecule. Cytokines, adhesion molecules and metalloproteinases are shed from melanoma cells into the serum, but these cells are not the only source of elevated serum levels. Several inflammatory conditions are responsible for high serum concentrations of these molecules. In general, they are not sensitive and specific enough to serve as "melanoma markers."

Biomarkers, Tumor↗
PubMed1983

Glutathione reductase activity in skin exposed to 4-tertiary butyl catechol.

The effect of 4-tertiary butyl catechol (TBC), a potent depigmenting chemical, on glutathione reductase (GR) in pigmented ear skin of hairless mice was investigated. Three topical applications of TBC, which cause neither skin color changes nor melanocyte degeneration, induced an increase in enzyme activity. Since the same treatment resulted in pheomelanin formation as evidenced by electron microscopy, it is suggested that the GR increase correlates at least in part with changes in melanocyte metabolism. This enzyme generates a reduced form of glutathione which may be involved in the formation of glutathionedopas, substrates for hydrolytic enzymes to produce cysteinyldopas, and pheomelanin. Elevation of GR may be an indication of melanogenesis before clinical skin color changes due to TBC appear. It may be used for the early detection of occupational leukoderma.

Animals↗
PubMed1977

Ocular melanomas: formaldehyde-induced fluorescence in relation to mortality.

Some ocular malignant melanomas contain enough cysteinyldopa to make them fluorescent when treated with formaldehyde. In 32 ocular malignant melanomas, such fluorescence was seen in 19 cases, which had a slightly, but not significantly, worse prognosis than the 13 cases with no fluorescence. The mixed type of malignant melanoma showed fluorescence significantly more often than the B type. Fluorescence histochemistry thus gives a biochemical classification of the tumor, but not a malignancy prognosis.

Adult↗
PubMed1985

Microanalysis of eumelanin and pheomelanin in hair and melanomas by chemical degradation and liquid chromatography.

A method for the quantitative analysis of eumelanin and pheomelanin in tissues, e.g., hair and melanoma, is described. The method is simple and rapid because it does not require the isolation of melanins from the tissues. The rationale is that permanganate oxidation of eumelanin yields pyrrole-2,3,5-tricarboxylic acid (PTCA) which may serve as a quantitatively significant indicator of eumelanin, while hydriodic acid hydrolysis of pheomelanin yields aminohydroxyphenylalanine (AHP) as a specific indicator of pheomelanin. The degradation products, PTCA and AHP, can be readily analyzed by high-performance liquid chromatography. Chemical degradations of synthetic melanins, prepared from dopa, 5-S-cysteinyldopa, and their mixtures in various ratios, gave PTCA and AHP in yields that correlated with the dopa/5-S-cysteinyldopa ratio. The PTCA/AHP ratio as well as the contents of PTCA and AHP reflected well the type of melanogenesis in hair and melanomas. The amounts needed for each degradation were 0.5 mg of melanin, 2 mg of hair, and 5 mg of tissue samples. As many as 20 samples can be analyzed within 3 working days.

Animals↗
PubMed1984

Ia-like antigen expression on biologically different human melanoma cell lines.

Ia-like antigen binding of a large panel of monoclonal antibodies (six anti-human Ia-like monoclonal antibodies and ten murine anti-Ia monoclonal antibodies cross-reactive with human Ia-like antigens) were compared on seven permanent human melanoma cell lines by radioimmunoassay. Cell lines were initiated from primary or metastatic tumors and presented various levels of tumorigenicity (assessed by heterotransplantation in nude mice) and pigmentation (shown by 5-S-cysteinyldopa determination and cytological data). Two cell lines originated from the same primary melanoma, while two other pairs of cell lines originated from superficial spreading melanoma or metastatic lymph node of the same patients. Identical Ia-like allodeterminants were found in cell lines of the same individual origin. Quantitative expression of beta 2-microglobulin and Ia-like antigens was similar in all cell lines except for one, in which these molecules were expressed in lower amounts. These results indicate that Ia-like antigen expression of the cell lines is unrelated to primary or metastatic origin, degree of pigmentation and ability to grow in nude mice.

Adult↗
PubMed1987

Photogeneration of free radicals from eumelanogenic intermediates and metabolites.

We have recently demonstrated that cysteinyldopas, pheomelanogenic precursors and excreted eumelanogenic metabolites, are photolabile and initiate DNA damage in vitro. In this study we have extended our photochemical investigations to eumelanogenic indole intermediates and metabolites. Continuous-wave photolysis of 5,6-dihydroxyindole (DHI), 5,6-dihydroxyindole-2-carboxylic acid (DHICA), or its 5-methoxylated metabolite (HMICA) with biologically relevant ultraviolet radiation (i.e., wavelengths greater than 300 nm) resulted in rapid destruction of starting material. Using ESR spin-trapping techniques we observed the initial production of free radical species; prolonged photolysis resulted in the formation of polymeric photoproducts. Radicals were trapped by the nitrone spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and characterized by their ESR spectra as hydrated electrons and hydrogen atoms. Experiments further demonstrated that while DHI photoionizes, the two indole-2-carboxylic acid derivatives do not ionize appreciably upon irradiation, rather homolysis of X-H bonds appears to be a significant photochemical pathway. The potential photobiological significance of melanogenic indole intermediates is discussed.

Chromatography, High Pressure Liquid↗
PubMed1995

Interaction of melanin with carbon- and oxygen-centered radicals from methanol and ethanol.

The interaction of dopa-melanin (DM) and cysteinyldopa-melanin (CDM) with carbon- and oxygen-centered radicals generated by benzophenone-photosensitized hydrogen abstraction from ethanol, or by pulse radiolysis of aqueous solutions of methanol and ethanol, is reported. Photosensitized formation of carbon-centered radicals and their interaction with melanin was monitored by electron paramagnetic resonance (EPR) spin trapping using DMPO, and via the melanin free radical signal itself. In the pulse radiolysis experiments, the interaction of DM or CDM with hydroxymethyl, hydroxyethyl, and the corresponding methanol peroxyl radical was monitored by recording time-dependent changes of the melanin absorbance at selected wavelengths. The data indicate that both melanins are good scavengers of carbon-centered radicals, with corresponding rate constants in the range of 10(7) to 10(8) M-1 s-1. Significantly, compared to DM, CDM is also an exceptionally efficient scavenger of oxygen-centered radicals derived from methanol with corresponding rate constants of 2.7 x 10(4) and 2 x 10(6) M-1 s-1 for DM and CDM, respectively. The results are discussed with reference to the potential role of melanin in protecting the integrity of melanosomes by inhibiting peroxidation of lipid components of the organelle membrane.

Benzophenones↗
PubMed1991

The neuromelanin of the human substantia nigra.

The pigment of the human substantia nigra was isolated after extraction of lipids and proteins with 2% sodium cholate in 30% ethanol followed by 2% sodium dodecyl sulfate in 10% glycerol. The pigment was hydrolysed with HI or degraded by treatment with KMNO4 and the samples were examined for compounds known to derive from pheomelanin (4-amino-3-hydroxyphenylalanine, AHP and 4-amino-3-hydroxyphenylethylamine, AHPEA), or from eumelanin (pyrrole-2,3,5-tricarboxylic acid, PTCA). The HI hydrolysis yielded AHPEA in large quantities, indicating cysteinyldopamine as the main source of the pheomelanin moiety of the neuromelanin, but also trace amounts of AHP, derived from cysteinyldopa oxidation products. Dopamine and small quantities of dopa were also obtained by HI hydrolysis of the neuromelanin. The yield of PTCA was low, but the amounts observed show that part of the neuromelanin is of the eumelanin type, a fact compatible with an occasional exhaustion of the glutathione-cysteine reduction system at the site of neuromelanin formation.

Chromatography, High Pressure Liquid↗
PubMed2001

Interaction of enkephalin derivatives with reactive oxygen species.

The oxidation of opioid peptides by tyrosinase in the presence of an excess of a thiol gives rise to cysteinyldopa derivatives. The major products arising from the reaction between Leu-enkephalin and cysteine are represented by 5-S-cysteinyldopaenkephalin (5-CDenk) and 2-S-cysteinyldopaenkephalin (2-CDenk). The interaction of 5-CDenk and 2-CDenk with reactive oxygen species (ROS) has been studied. These compounds are able to scavenge superoxide anion, hydroxyl and peroxyl radicals as well as to reduce the lipid peroxidation rate induced by ABAP. The scavenging activities in all instances are dose-dependent. In some cases CDenks are more active than compounds recognized as strong radical scavengers, such as Trolox and mannitol. As a result of the action of the Fenton system, the CDenks (as well as the Enks) are oxidized into pigmented derivatives. The possible implications of the interaction of CDenks and Enks with ROS on melanization process in Parkinson's disease are discussed.

Animals↗
PubMed2001

Cysteine and indole derivatives as markers for malignant melanoma.

Malignant melanoma is a skin tumour, which carries a very unfavourable prognosis. The early detection of a melanoma and even more its metastasis is of decisive importance for the survival prognosis of the patients. So there is always a desire for simple, economical and meaningful serological markers. From the cysteine- and indole-related derivatives, 5-S-cysteinyldopa (5-SCD) and 6-hydroxy-5-methoxy-indole-2-carboxylic acid (6H5MI2C) are the most important substances for this purpose. For 5-SCD, the sample pretreatment was carried out either by a manual extraction onto alumina, by an automated method onto boronic acid affinity gels or by an automated solid-phase extraction. For 6H5MI2C, liquid-liquid extractions or direct injection techniques were applied. The chromatographic analyses in the early years were mostly performed with GC-MS. Today HPLC is the nearly exclusively used separation technique. For HPLC, standard RP18 separating columns and usual compositions of eluents were applied. As detectors both the ECD and the FD showed a sufficient sensitivity and selectivity. 5-SCD and 6H5MI2C are very sensitive to light and oxidation. These properties must be taken into account in the complete analysis procedure, including the sample collection, otherwise false low values will result especially for plasma samples. For a critical discussion of the analytical methods and still more for the interpretation of the obtained results, the detailed analytical procedures must be considered. 5-SCD in plasma is one of the best markers of malignant melanoma. It shows an excellent specificity and also an adequate sensitivity in the metastatic melanoma stages. For the detection of primary melanomas and for urine instead of plasma samples, the sensitivity of 5-SCD is generally lower. Altogether, the sensitivity of this parameter is not yet sufficient. 6H5MI2C and other indole derivatives have been investigated far less than 5-SCD. 6H5MI2C correlates less clearly with the different stages of the melanoma and is therefore a less suitable marker. To improve the sensitivity of the findings, in future the investigations should be performed as multi-marker analysis with the simultaneous measurements of more than one marker substance in a given patient sample. Not only one measurement should be carried out per patient, it would be more meaningful to observe the patients with laboratory diagnostics in the follow-up.

Biomarkers, Tumor↗
PubMed1999

Free radical scavenging properties of melanin interaction of eu- and pheo-melanin models with reducing and oxidising radicals.

The human skin and eye melanin is commonly viewed as an efficient photoprotective agent. To elucidate the molecular mechanism of the melanin-dependent photoprotection, we studied the interaction of two synthetic melanins, dopa-melanin and cysteinyldopa-melanin, with a wide range of oxidising and reducing free radicals using the pulse radiolysis technique. We have found that although both types of free radicals could efficiently interact with the synthetic melanins, their radical scavenging properties depended, in a complex way, on the redox potential, the electric charge and the lifetime of the radicals. Repetitive pulsing experiments, in which the free radicals, probing the polymer redox sites, were generated from four different viologens, indicated that the eumelanin model had more reduced than oxidised groups accessible to reaction with the radicals. Although with many radicals studied, melanin interacted via simple one-electron transfer processes, the reaction of both melanins with the strongly oxidising peroxyl radical from carbon tetrachloride, involved radical addition. Our study suggests that the free radical scavenging properties of melanin may be important in the protection of melanotic cells against free radical damage, particularly if the reactive radicals are generated in close proximity to the pigment granules.

Free Radical Scavengers↗