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

An experimental study using human melanoma (NEL-MI), rat hepatoma (Fu5-5), and human kidney (293-31) cell lines was undertaken in order to evaluate the antitumor activity of 4-hydroxyanisole (4-OHA) in vitro. Prior reports have indicated highly specific antitumor activity of 4-OHA against melanoma cells in vitro. This specific antitumor activity has been proposed to be due to the oxidation of 4-OHA by tyrosinase to cytotoxic oxidation products. Dose-dependent cytotoxicity was observed when cells were cultured for 72 h in the presence of 4-OHA. At 100 microM, 4-OHA produced growth inhibition of 62%, 32%, and 55% in melanoma, hepatoma, and kidney cell lines, respectively. No effect was seen at 10 microM 4-OHA. 1,000 microM 4-OHA produced 100% kill. Tyrosinase activity was detected only in melanoma cells. The effect of 100 microM 4-OHA on the incorporation of 3H DNA precursors in melanoma, hepatoma, and kidney cells was also studied. Thymidine incorporation was inhibited in all three cell lines at the lowest cell density tested, with the greatest inhibition seen on melanoma cells. As cell density increased, the effect of 4-OHA on thymidine incorporation decreased. With respect to RNA synthesis, 4-OHA significantly reduced the incorporation of uridine in all three cell lines, with the greatest effect in melanoma cells. Cell density also affected the inhibition of uridine incorporation, but to a lesser extent than that observed on thymidine incorporation. The effect of 4-OHA on leucine incorporation was modest and uninfluenced by cell density. Thus, cytotoxicity of 4-OHA may involve two different mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Specificity of growth inhibition of melanoma by 4-hydroxyanisole. 249 44

A distinguishing characteristic of cells of the melanocyte lineage is the expression of the melanosomal enzyme tyrosinase that catalyzes the synthesis of the pigment melanin. A tyrosinase cDNA clone, designated BBTY-1, was isolated from a library constructed from the pigmented TA99+/CF21+ melanoma cell line SK-MEL-19. Expression of BBTY-1 in mouse L929 fibroblasts led to synthesis and expression of active tyrosinase, and, unexpectedly, to stable production of melanin. Melanin was synthesized and stored within membrane-bound vesicles in the cytoplasm of transfected fibroblasts. BBTY-1 detected a 2.4-kb mRNA transcript in nine of nine pigmented, tyrosinase-positive melanoma cell lines. Tyrosinase transcripts of the same size and abundance were detected in a subset (three of eight) of nonpigmented, tyrosinase-negative melanoma cell lines, suggesting that post-transcriptional events are important in regulating tyrosinase activity. Two melanocyte antigens, recognized by mAbs TA99 and CF21, that are specifically located within melanosomes and are coexpressed with tyrosinase activity, did not react with transfected mouse fibroblasts expressing human tyrosinase, supporting the conclusion that these antigenic determinants are distinct from the tyrosinase molecule coded for by BBTY-1.
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PMID:Induction of pigmentation in mouse fibroblasts by expression of human tyrosinase cDNA. 249 55

Tyrosinase synthesis and its posttranslational processing was compared in hair follicular melanocytes of C3H-HeAvy mice during eumelanogenesis and phaeomelanogenesis. Tyrosinase activity was increased during eumelanogenesis and this was paralleled by an increase in tyrosinase synthesis, as measured by the incorporation of [35S]methionine. Although tyrosinase activity was lower during phaeomelanogenesis there was no change in tyrosinase synthesis. alpha-Melanocyte stimulating hormone (alpha-MSH) increased tyrosinase activity and its synthesis during eumelanogenesis but not during phaeomelanogenesis. Bromo-adenosine 3,5-cyclic monophosphate sodium salt (8-bromo-cAMP) was similarly effective during eumelanogenesis, but unlike alpha-MSH stimulated tyrosinase synthesis during phaeomelanogenesis. This suggests that during phaeomelanogenesis the melanocytes may fail to express MSH receptors. This cannot account for the lower tyrosinase activity, however, for alpha-MSH acts predominantly at the level of tyrosinase synthesis and this was similar during eumelanin and phaeomelanin production. The reduced tyrosinase activity is, therefore, presumably due to some posttranslational change. Accordingly, less tyrosinase was associated with the melanosomal fraction during phaeomelanogenesis than during eumelanogenesis. Glycosylation of tyrosinase, as measured by the incorporation of [3H]glucosamine was also reduced during phaeomelanogenesis. Although 8-bromo-cAMP increased glycosylation of tyrosinase in both eumelanin and phaeomelanin producing melanocytes, it failed to alter the subcellular distribution of the enzyme. It would appear that, although glycosylation of tyrosinase is lower during phaeomelanogenesis, the reduced tyrosinase expression is the result of decreased uptake of tyrosinase by the melanosome.
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PMID:Regulation of tyrosinase synthesis and its processing in the hair follicular melanocytes of the mouse during eumelanogenesis and phaeomelanogenesis. 250 79

Tyrosinase activity was compared in the skin and hair bulbs of young black and agouti mice between 4 and 12 days old. Differences in activity were found to be maximal in both the hair and skin at the time of yellow pigment synthesis in agouti mice. Histological examination suggested that the number of dopa-positive melanocytes is similar in the hair bulbs of agouti and black mice. The level of SH-compounds in the hair bulb was examined and found to be elevated in agouti tissue at the time of phaeomelanin formation. It was shown that sulphydryl compounds such as cysteine and glutathione have an inhibitory effect on tyrosinase, and it is possible that the elevated levels of SH-compounds are responsible for a reduction in tyrosinase activity in agouti mice. In agouti hair bulbs, this effect can be reversed in vitro by addition of copper.
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PMID:Tyrosinase activity in the first coat of agouti and black mice. 251 68

Tyrosinase activity was tested on some tyrosine-containing peptides (enkephalins and exorphins). All they are substrates for tyrosinase, showing a good affinity for the enzyme, in some cases higher than tyrosine itself. Aminoacid analysis after hydrolysis of long-lasting incubation mixtures of tyrosinase with Leu-enkephalin in presence of reductants demonstrates the formation of DOPA. The production of a new peptide containing DOPA derived from the oxidation of Leu-enkephalin was revealed by high performance liquid chromatography (HPLC).
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PMID:Enkephalins and exorphins oxidation by tyrosinase. 251 78

Mouse melanoma cells in culture respond to melanocyte-stimulating hormone (MSH) by demonstrating increased activity of tyrosinase, the rate-limiting enzyme for melanin synthesis. Because this stimulation is strictly dependent upon continued transcription and translation, we have carried out studies to determine if MSH increases the level of tyrosinase mRNA. The abundance of tyrosinase message levels in melanoma cells treated with either MSH or dibutyryl cAMP was determined by Northern blot analysis utilizing a 946 base pair mouse tyrosinase cDNA probe. The tyrosinase cDNA was isolated from a lambda gt11 expression library generated from mRNA isolated from theophylline-induced Cloudman melanoma cells. The abundance of tyrosinase mRNA was determined in an amelanotic cell clone (AM-7AS) and a melanotic cell clone (MEL-11AS). The melanotic cell line had five times as much tyrosinase activity and almost 10 times more tyrosinase mRNA than the amelanotic line. Tyrosinase activity and mRNA increased in both cell lines after MSH addition. The amelanotic line treated with MSH for three days showed a fivefold increase in tyrosinase activity and a twofold increase in tyrosinase mRNA. The melanotic cell line treated with MSH for three days showed a 3.7-fold increase in enzyme activity and an eightfold increase in the abundance of tyrosinase mRNA. Dibutyryl cAMP also stimulated tyrosinase activity and the accumulation of tyrosinase mRNA. The data suggest that MSH, acting through cAMP, promotes an accumulation of tyrosinase mRNA.
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PMID:Regulation of tyrosinase mRNA levels in mouse melanoma cell clones by melanocyte-stimulating hormone and cyclic AMP. 254 86

In Bomirski Ab amelanotic hamster melanoma cells, L-tyrosine and/or L-dopa induce increases in tyrosinase activity as well as synthesis of melanosomes and melanin. L-tyrosine also modifies melanocyte-stimulating hormone (MSH) binding. In this paper we show that in the Bomirski amelanotic melanoma system MSH and agents that raise intracellular cyclic AMP induce dendrite formation, inhibit cell growth, and cause substantial increases in tyrosinase activity without inducing melanin synthesis. Tyrosinase activity is detected only in broken cell preparations, or cytochemically in fixed cells. In the continued absence of mature melanosomes, the induced enzyme remains in elements of the trans-Golgi reticulum. Comparative measurements of cyclic AMP in amelanotic and tyrosine-induced melanotic cells show similar basal levels. L-tyrosine and L-dopa have little or no effect, whereas MSH may cause a 1000% peak increase in cyclic AMP levels both in amelanotic and melanotic cells. None of these agents influences cyclic GMP or inositol trisphosphate (InsP3) levels. In agreement with the InsP3 assays, phorbol ester (TPA) has no effect on melanization, tyrosinase activity or cell proliferation. In conclusion, in the Bomirski amelanotic melanoma, MSH induces only partial cell differentiation associated with raised levels of cyclic AMP. Induction of melanosome synthesis and melanization by L-tyrosine or L-dopa appear to follow pathways unrelated to cyclic AMP, cyclic GMP or InsP3.
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PMID:MSH inhibits growth in a line of amelanotic hamster melanoma cells and induces increases in cyclic AMP levels and tyrosinase activity without inducing melanogenesis. 255 57

Tyrosinase was isolated from cultured melanoma cells using a procedure involving solubilization of the enzyme by means of Triton X-100, followed by different types of chromatography and tryptic digestion to make the enzyme soluble even in the absence of detergent. Starting with a membranous material containing 72 mg protein, 0.21 mg tyrosinase was obtained. The recovery of tyrosinase was 36% of the quantity found in the membranous starting material. In order to acquire a completely purified enzyme preparation suitable for amino acid sequence analysis, SDS-PAGE followed by blotting onto a polyvinylidene difluoride membrane was performed as a final step. The apparent molecular weight was found to be 66,000. Determination of the amino acids of the aminoterminal portion by automated Edman degradation showed the following sequence: His-Phe-Pro-Arg-Ala-X-Val-Ser-Ser-Lys-Asn-Leu-Met-Glu-Lys-Glu-X-X-Pro-Pr o-The enzyme purified has an amino acid sequence identical with that of human tyrosinase deduced from c-DNA by Kwon et al. Striking similarities between our amino acid sequence and that predicted by Yamamoto et al. from mouse tyrosinase c-DNA were also observed.
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PMID:Isolation of human tyrosinase from cultured melanoma cells. 256 29

Tyrosinase activity was increased in hair follicular melanocytes of C3H-HeAvy mice during the hair cycle and reached higher levels on days 6-8 after plucking than on day 12. Similarly, the rate of incorporation of [35S]methionine into tyrosinase was greater on days 6-8 than on day 12, but the relative difference was much less. alpha-MSH had no effect on tyrosinase activity or the rate of [35S]methionine incorporation on day 12 and, while it increased both on days 6 and 8, it had a greater effect upon the latter. Pulse-chase experiments showed that the half-life of tyrosinase was 3.5 h and that this was unaffected by alpha-MSH. The results indicate that the increases in tyrosinase activity which occur during the hair cycle involve changes in both the synthesis and activation of the enzyme and that the predominant effect of alpha-MSH is on the former of these two processes.
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PMID:Regulation of tyrosinase synthesis by alpha-melanocyte-stimulating hormone in hair follicular melanocytes of the mouse. 282 5

Four human melanoma cell lines were examined for their responsiveness to the hormones 1,25-dihydroxyvitamin D3 (1,25[OH]2D3), calcitonin, and parathyroid hormone (1-34). Cells from each of the 4 lines contained high affinity binding sites for 1,25(OH)2D3. At high cell densities, binding of 1,25(OH)2D3 was diminished due to a decrease in receptor number with no apparent change in affinity. Preincubation with 1,25(OH)2D3 (10(-10) to 10(-8) M) increased tyrosinase activity 1.3- to 3.2-fold and 25-hydroxyvitamin D3-24-hydroxylase activity 1.4- to 10-fold. Human calcitonin (0.82 to 82.5 ng/well) raised the intracellular concentration of cyclic adenosine monophosphate 1.4- to 9.4-fold. Tyrosinase activity increased in response to calcitonin in 2 of the cell lines, decreased in the third, and showed no change in the fourth. Human parathyroid hormone (1-34) in concentrations of 1 to 10 ng/ml produced no significant changes in cyclic adenosine monophosphate accumulation, cell numbers, or tyrosinase activity in any of the cell lines. This study indicates that the phenotype of human melanoma cells can be modulated by the calciotropic hormones 1,25(OH)2D3 and calcitonin.
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PMID:Human melanoma cells: functional modulation by calciotropic hormones. 283 16


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