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

Tyrosinase in a melanosome is known to be inactivated during melanin formation in vivo, and a similar inactivation was observed in vitro when melanosomes isolated from Harding Passey mouse melanoma were incubated with dopa. Tyrosinase, whether particle bound or in soluble form, was inactivated during the dopa-tyrosinase reaction and the reduction rate of its activity was proportional to the reaction time. Tyrosinase inactivation also occurred when ascorbic acid was added to the reaction system; in which dopaquinone, an oxidation product of dopa which is immediately converted back to dopa by ascorbic acid thus preventing melanin formation. When 14C-dopa or 14C-ascorbic acid were added to the reaction mixture, these radioactive substances were not recovered from the inactivated enzyme protein fraction after incubation. In addition this inactivation of tyrosinase by dopa was not inhibited by any of: 1.4-diazabicyclo[2.2.2]octane, scavenger for singlet oxygen; D-mannitol, that for hydroxyl radical; superoxide dismutase, that for superoxide anion; and catalase, cleavaging enzyme for hydrogen peroxide. Thus the inactivation of tyrosinase appears to be due to neither these radicals, nor reaction products from dopa or ascorbic acid, but to changes in the enzyme itself.
 ...
PMID:Inactivation of tyrosinase by dopa. 677 5

Recent studies have demonstrated that preincubation of SK-Mel-28 melanoma cells with ferric ammonium citrate (FAC) resulted in marked stimulation of 59Fe uptake from 59Fe-125I-transferrin (Tf), but only at Tf concentrations above that required for saturation of the Tf receptor (Richardson and Baker (1992) J. Biol. Chem. 267, 13972-13979). The mechanism responsible for this stimulation was unknown and is the subject of the present report. Preincubation of cells with FAC (25 micrograms/ml), followed by a 2 h incubation with 59Fe-125I-Tf (0.1 mg/ml; 1.25 microM), resulted in temperature-dependent 59Fe uptake to approx. 200% of the control value. Furthermore, the effect was not specific for melanoma cells and was also observed in other normal and neoplastic cells. Preincubation of melanoma cells with FAC also stimulated 59Fe uptake from 59Fe-citrate, but to a far greater extent than that observed with 59Fe-125I-Tf (viz., > 20-fold that seen for the control). Interestingly, neither receptor-mediated endocytosis nor the postulated diferric Tf reductase were involved in the FAC-activated Fe uptake process from Tf. However, the addition of free radical scavengers to FAC such as catalase, superoxide dismutase, ceruloplasmin, Hepes, mannitol and high concentrations of BSA or ascorbate, markedly depressed FAC-activated 59Fe uptake from 59Fe-125I-Tf and 59Fe-citrate. These agents when added to control cells had no effect on 59Fe uptake. The addition of superoxide generating agents and hydrogen peroxide to minimum essential medium (MEM) containing FAC but not to MEM alone, also stimulated 59Fe uptake. These data suggest that the initial activation of the FAC-stimulated Fe uptake system was caused by the production of hydroxyl radicals via the Fe-catalysed Haber-Weiss reaction. We propose that this Fe uptake process represents an important cellular defense mechanism against oxidant stress generated in the presence of low-molecular-weight Fe complexes.
 ...
PMID:Identification of a mechanism of iron uptake by cells which is stimulated by hydroxyl radicals generated via the iron-catalysed Haber-Weiss reaction. 748 42

X-rays were used to induce melanin biosynthesis in brown and black guinea pigs in vivo. During the course of pigmentation, the expression of thioredoxin reductase was increased, whereas for the other antioxidant enzymes, superoxide dismutase (cytosol Cu/Zn-enzyme), catalase, and glutathione reductase, levels and activities decreased. Isobutylmethylxanthine induced eumelanin biosynthesis in murine melanoma cells (Cloudman S-91). In these cells, thioredoxin reductase levels coincided with melanogenesis. Our results suggest that both tyrosinase and thioredoxin reductase respond to oxidative stress in the epidermis as well as in melanoma cells and react with superoxide anion radicals to stimulate melanogenesis and to prevent peroxidative damage, respectively.
 ...
PMID:Thioredoxin reductase induction coincides with melanin biosynthesis in brown and black guinea pigs and in murine melanoma cells. 752 41

The present study was carried out to examine the role of reactive oxygen species in mediating the melanogenic effects of UVR. B16 mouse melanoma cells responded to a single dose of UVR by showing increases in their melanin content. Although there was a small increase in melanin at 48-72 hours, which was associated with a rise in tyrosinase activity at 48 h, the greatest change occurred at 3 h and this was not associated with an increase in tyrosinase activity. This short-term response, unlike the more delayed melanogenic response, was reduced by superoxide dismutase (SOD). Xanthine oxidase (XO), which generates the superoxide anion (O2-), also increased the melanin content of B16 melanoma cells with effects at 3 h and 48 h. As with UVR, the delayed response was accompanied by an increase in tyrosinase activity but no such association was evident at 3 h. In addition, the short-term effect, like that seen with UVR, was reduced with SOD and to a lesser extent with catalase. In contrast to the effects found with XO, glucose oxidase, which generates hydrogen peroxide, had no effect on the melanin content or tyrosinase activity of the B16 cells. These results confirm previous observations that UVR is able to act directly on cells to bring about delayed increases in melanogenesis. They further demonstrate that UVR also stimulates melanogenesis through a more rapid action that is not associated with an activation of tyrosinase. This effect could be mediated by the O2- which, rather than activating tyrosinase, could act by serving as a substrate for the enzyme.
 ...
PMID:The superoxide anion may mediate short- but not long-term effects of ultraviolet radiation on melanogenesis. 795 23

Low plasma selenium levels have been linked to increased risk of non-melanoma skin cancer in humans. The present study examined the relationship between selenium level in the diet and development of skin tumors induced by ultraviolet radiation in female Skh:HR-1 hairless mice. Animals were maintained on a torula yeast-based diet containing either 0, 0.1, or 0.5 mg/kg selenium as Na2SeO3. Ultraviolet light at a dose of 90 mJ/cm2, three times weekly for 20 weeks, resulted in skin tumors in all groups. Following cessation of ultraviolet light exposure, tumors continued to increase in selenium-deficient mice and those fed only 0.1 mg/kg, but leveled off for those on 0.5 mg/kg. During the carcinogenesis process, epidermal antioxidant enzymes catalase, superoxide dismutase, and glutathione peroxidase were monitored. Selenium deficiency decreased glutathione peroxidase and resulted in an early increase in superoxide dismutase and catalase in response to ultraviolet light treatment. These results indicate that dietary Se may be an important chemopreventive agent for skin cancer.
 ...
PMID:Effects of dietary selenium on UVB-induced skin carcinogenesis and epidermal antioxidant status. 817 60

Reactive oxygen species (ROS) have been frequently implicated in the initiation and promotion phases of carcinogenesis. Antioxidant enzymes, which can antagonize this process, are lowered in a number of malignancies. The enzyme most commonly decreased is the mitochondrial Mn-containing superoxide dismutase (MnSOD) encoded by a nuclear gene mapped on the band 6q21, a region frequently deleted in several human tumours. The close association of del(6q) with diminution of MnSOD has led to suggest that MnSOD might be a new type of tumour-suppressor gene. This hypothesis is also sustained by the finding that transfection of MnSOD cDNA into human melanoma cell lines suppress the malignant phenotype. There are, however, conflicting observations that tend to ascribe the deficiency of the MnSOD activity more to a defect in the expression of the gene than to its deletion. In many transformed cell lines, including some with marked del(6q), there is no change in the dosage of the MnSOD gene and the enzyme is highly inducible by various pro-oxidant agents. Transition metals (Mn, Fe) have been found to be highly deficient in human and rodent tumours. Owing to the second messenger function of ROS in activating transcription factors (NF-kB, AP-1) and to the ability of Mn to facilitate the dismutation of O2- to H2O2 and of Fe to participate in the Fenton reaction, we propose that in the early stage of carcinogenesis an impairment of the signal transduction machinery, related to the metal deficiency, might limit the binding to DNA of transcription factors and cause the defect in the MnSOD gene expression.
 ...
PMID:Defective gene expression of MnSOD in cancer cells. 826 40

The protective role of melanin, either synthetic or derived from a metastatic lung melanoma nodule, was studied in terms of its ability to interact with active oxygen species (O2., H2O2, RO., ROO., etc.). Both melanins showed the ability to react with O2.. The superoxide dismutase-like activity corresponds to 21 and 10 U/mg for synthetic and tumor melanin, respectively. The latter value accounts for about 8% of the superoxide dismutase activity of cultured melanoma cells. Neither type of melanin showed catalase-like or glutathione peroxidase-like activity. Both types of melanin reacted with RO. and ROO. radicals as determined by inhibition of the lipid peroxidation reaction of rat liver homogenates. The spontaneous lipid peroxidation of rat liver homogenate was inhibited up to 90% and 80% by synthetic and tumor melanin with half-maximal effects at 2.5 and 5.5 micrograms melanin/ml, respectively. The 2,2-azo-bis-(2 amidino propane) (AAPH)-initiated lipid peroxidation of rat liver homogenate was inhibited up to 30% and 20% by synthetic and tumor melanin, with half maximal effect at 120 and 500 micrograms melanin/ml, respectively. Both types of melanin were able to protect the in vitro inactivation of glucose oxidase, which occurs in the presence of AAPH-generated radicals.
 ...
PMID:Role of melanin as a scavenger of active oxygen species. 830 73

The effects of systems generating active oxygen species (superoxide anion, hydrogen peroxide, hydroxyl radical) on tyrosinase have been studied in cultured human melanoma cells. Tyrosinase activity was determined by measuring the quantity of 5-S-L-cysteinyl-L-dopa (5-S-CD) formed in the presence of D,L-dopa and L-cysteine. In some experiments, the enzyme protein was determined by radio immunoassay [RIA]. Exposure of cells to xanthine/xanthine oxidase or glucose/glucose oxidase resulted in a dose-related elevation of tyrosinase. Catalase, but not superoxide dismutase, prevented this increase indicating that hydrogen peroxide may be the agent responsible for the action, whereas superoxide anion is not involved. Hydroxyl radicals formed by the Haber-Weiss or Fenton type reactions were not found to produce elevation of tyrosinase. Catalase determinations showed no enzyme in the medium but a high concentration in the cells. Inhibition of intracellular catalase by 3-amino-1,2,4-triazole caused an increase in the tyrosinase level. The effects of dopac, xanthine/xanthine oxidase, and glucose/glucose oxidase all producing hydrogen peroxide, and increasing tyrosinase, were enhanced by the inhibition of catalase. It is concluded that hydrogen peroxide, formed by the systems, accounts for the elevation of tyrosinase level. When tyrosinase activities determined by 5-S-CD formation were compared to enzyme amounts found by RIA, the ratios of these values were always constant. This fact indicates that the increase in the tyrosinase activities was not due to an activation of the enzyme, but mirrored the quantities of enzyme protein present in the samples. On the basis of our findings, it is assumed that hydrogen peroxide is a regulator of tyrosinase in normal melanocytes and melanoma cells.
 ...
PMID:Hydrogen peroxide as an inducer of elevated tyrosinase level in melanoma cells. 843 9

Sodium 5,6-benzylidene ascorbate (SBA) is a conjugate of ascorbic acid (Asc) with benzyaldehyde. It has been found that the antioxidant activity of SBA is more stable and has a longer lifetime in living cells and organs than Asc. In this study, we investigated the effect of SBA on the induction of melanin in cultured melanoma (B-16) cells irradiated by UV-A. Melanin content of B-16 cells was significantly increased by UV-A irradiation. The induction was abolished by mannitol and particularly by superoxide dismutase, suggesting the involvement of O2- in the biosynthesis of melanin in cultured melanoma cells. This was theorized by the fact that the induction was also observed in B-16 cells treated with superoxide anion radicals chemically generated in the hypoxanthine/xanthine oxidase-reaction system, instead of UV-A irradiation. The induction of melanin caused by UV-A irradiation was suppressed by SBA in a dose-dependent manner. To elucidate the mechanism of this suppressive effect, the scavenging activity against O2-, and the inhibitory effect of SBA on tyrosinase activity were examined. ESR spectrometric analysis showed that SBA strongly scavenged O2-, and the presence of SBA in the medium remarkably inhibited the tyrosinase activity in cultured B-16 melanoma cells. It can be concluded that SBA effectively inhibits the melanin biosynthesis in B-16 melanoma cells induced by reactive oxygen species (ROS) generated by UV-A irradiation via tyrosinase.
 ...
PMID:Inhibitory effect of sodium 5,6-benzylidene ascorbate (SBA) on the elevation of melanin biosynthesis induced by ultraviolet-A (UV-A) light in cultured B-16 melanoma cells. 853 99

Malignant melanoma in its disseminated stage is incurable. The most widely accepted criteria for the prognostic evaluation of melanoma are histopathological and clinical parameters, and the identification of additional simple, serological tumour markers is thus of paramount importance. Manganese-containing superoxide dismutase (MnSOD) belongs to a family of metalloproteins that catalyse the metabolization of oxygen radicals in order to protect these cells from radical damage. In patients with epithelial ovarian carcinomas, serum MnSOD levels have been shown to be elevated in accordance with the progression of their clinical disease. Recently, an overexpression of MnSOD was shown to suppress the malignant phenotype of human malignant melanoma cells. Therefore, we determined serum MnSOD concentrations in 33 patients with malignant melanoma at different clinical stages. Whereas MnSOD serum levels in normal subjects (n = 11) and in dermatological patients with type I allergies (n = 10) or chronic non-allergic urticaria (n = 7) were below 200 ng/ml, the MnSOD serum concentrations in melanoma patients were statistically elevated in all clinical stages compared with normal (p < 0.005). These data suggest that elevated MnSOD serum concentrations correspond to tumour load and correlate with progression of malignant melanoma. Measurement of MnSOD serum levels might therefore provide a sensitive tool for monitoring the clinical course of melanoma.
Melanoma Res 1995 Oct
PMID:Serum manganese superoxide dismutase is a new tumour marker for malignant melanoma. 854 26


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