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)

Because glycosylation-dependent melanization inhibition induced in cultured B-16 melanoma cells by glucosamine is reversible, producing synchronized initiation of melanogenesis after its removal, we have analyzed the possible dynamics of initial melanogenesis through their interruption by glutathione. The addition of glutathione at 0.2% concentration to the theophylline-stimulated recovery process completely interrupts the initiation of melanization for at least 72 h. At the electron microscopic level, theophylline-treated cells have many vacuolar melanosomes with distinct pigmentation which contain some vesicles (64% of total premelanosomes) or amorphous, filamentous, or granular materials within the interior which are suggestive of pheomelanotic melanosomes. The addition of glutathione induces a complete absence of melanization in the premelanosomes, within which a filamentous interior with periodicity is generally re-formed with almost complete disappearance of internal vesicles, providing dramatic changes to the size and shape characteristic of eumelanotic melanosome. Electron microscopic dopa reaction of glutathione-treated cells shows a predominant localization of tyrosinase activity in the Golgi-associated endoplasmic reticulum-lysosome and coated vesicles, but not in premelanosomes, in contrast to their dispersed distribution in all melanogenic organelles in the theophylline-treated control, suggesting a lack of tyrosinase translocation. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of tyrosinase in the large granule fraction shows that in analogy with electron microscopic observations, glutathione blocks the reappearance of membrane-bound T3 tyrosinase which occurs in the theophylline-treated control during the recovery process, whereas the dynamics of T1 tyrosinase is almost the same as that of the control. These findings suggest that glutathione provides a new situation of interrupted melanogenesis in which melanization cannot proceed despite complete formation of melanosome matrix structure and a lack of inhibition of cellular metabolisms including protein glycosylation.
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PMID:Analysis of initial melanogenesis including tyrosinase transfer and melanosome differentiation through interrupted melanization by glutathione. 250 95

Coated vesicles have been found to contain much higher tyrosinase and gamma-glutamyl transpeptidase activities than premelanosomes. This indicates that similar to tyrosinase, gamma-glutamyl transpeptidase, an enzyme responsible for pheomelanogenesis, is highly concentrated in coated vesicles after its maturation in Golgi associated endoplasmic reticulum (GERL). Furthermore, in the pre- and post-dopaquinone melanogenic pathway, coated vesicles convert dopachrome to colorless indole compounds more quickly than in premelanosomes because of their higher dopachrome conversion factor activity. Melanosomes have been found to exhibit indole conversion factor activity, while coated vesicles show indole blocking factor activity. In moderately tyrosinase-rich premelanosomes, the levels of dopachrome conversion factor and indole blocking factor are lower than in coated vesicles or melanosomes. High levels of indole blocking factor in coated vesicles may indicate why melanin polymer formation does not occur there in vivo despite their high tyrosinase activity.
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PMID:Melanogenic regulatory factors in coated vesicles from melanoma cells. 257 41

Golgi complex and endoplasmic reticulum (ER) were isolated from suspension-cultured cells of sycamore (Acer pseudoplatanus L.) by stepwise sucrose density gradient centrifugation using protoplasts as starting material. The purity of the two organelle fractions isolated was assessed by measuring marker enzyme activities. Localization of glycolipid and glycoprotein glycosyltransferase activities in the isolated Golgi and ER fractions was examined; three glycosyltransferases, i.e., galactosyltransferase, fucosyltransferase, and xylosyltransferase, proved to be almost exclusively confined to the Golgi, whereas the ER fractions contained glycolipid glycosyltransferase. The Golgi complex was further subfractionated on a discontinuous sucrose density gradient into two components, migrating at densities of 1.118 and 1.127 g/cm3. The two fractions differed in their compositional polypeptide bands discernible from Na-dodecylsulfate gel electrophoresis. Galactosyltransferase distributed nearly equally between the two protein peaks and xylosyltransferase activities using the endogenous acceptor also appeared to be localized in the two subcompartments. By contrast, fucosyltransferase, engaged in the terminal stage of glycosylation, banded in the lower density fractions. Golgi-specific alpha-mannosidase, which is presumably engaged in the sugar trimming of Asn-N-linked glycoprotein carbohydrate core, was enriched fourfold in specific activity in the fractions of the higher density. The overall experimental results indicate that the cotranslational glycosylation of Asn-N-linked glycoproteins, e.g., polyphenol oxidase (laccase), takes place in the ER, while subsequent post-translational processing of the oligosaccharide moiety proceeds successively in the two physically separable compartments of the Golgi complex.
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PMID:Golgi-specific localization of transglycosylases engaged in glycoprotein biosynthesis in suspension-cultured cells of sycamore (Acer pseudoplatanus L.). 309 42

A spontaneous, hypomelanotic variant (MI) of the highly melanotic transplantable hamster melanoma of Bomirski (Ma) is the subject of this report. Tyrosinase activity is 2-3 times higher, but melanin content significantly lower than in the parental Ma melanotic melanoma. Acid phosphatase activity is similar in both, but beta-glucuronidase and aryl-sulfatase A are 2-3 times higher in the hypomelanotic variant. Transplanted MI melanomas grow more slowly than the parental tumor, but metastasize with similar incidence and localization. Hypomelanotic variant melanoma cells, even those in grossly nonnecrotic parts of the transplants, show signs of low viability like swelling of the cytoplasm or cellular condensation, and disintegration. Autophagic vacuoles are numerous. They appear to be formed by enclosure of a portion of cytoplasm by cisternae of smooth endoplasmic reticulum or trans-Golgi network. These limiting cisternae contain tyrosinase as evidenced by deposition of electron dense reaction product on incubation with tyrosine or DOPA. Other sites of ultrastructural tyrosinase reaction are melanosomes and the smooth-surfaced cisternae and vesicles of the trans-Golgi network. We postulate the low cell viability, associated with autophagosome formation, is the cause for the growth retardation of the MI variant, and that the lower melanin content of these tyrosinase-rich cells is due to sequestration of a substantial portion of newly synthesized enzyme into autophagic vacuoles before it has the chance of being incorporated into melanosomes.
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PMID:Pathology and ultrastructural characteristics of a hypomelanotic variant of transplantable hamster melanoma with elevated tyrosinase activity. 311 4

Previously, we have developed a mouse monoclonal antibody (MoAb) HMSA-1 (human melanosome-associated antigen-1) against the melanosome fraction of human malignant melanoma, and demonstrated the selective distribution of the HMSA-1 in neoplastic melanocytes on routine paraffin sections. This study examined, by using enzyme linked immunosorbent assay (ELISA) and immunoelectron microscopy, the subcellular distribution of the HMSA-1 in malignant melanocytes. Fractionation of cell organelles and ELISA assay indicated that the HMSA-1 is rich in fractions of large granule, melanosome and endoplasmic reticulum (ER) in melanoma cells. Immunoelectron microscopic study showed that the HMSA-1 is localized in the melanosomes of various developmental stages and vacuolar structures, which appeared to be the stage I melanosomes and which contained the matrix protein. Dopa cytochemistry revealed that the distribution of MoAb HMSA-1 reaction product is localized in the area different from that of tyrosinase, indicating that the synthetic processes of melanosomal matrix protein and tyrosinase are different. Furthermore, the reaction product with MoAb HMSA-1 was seen in the rough ER, indicating that the melanosomal matrix protein is synthesized by membrane-bound ribosomes and processed through the channel of ER.
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PMID:Immunoelectron microscopic demonstration of human melanosome associated antigens (HMSA) on melanoma cells: comparison with tyrosinase distribution. 312 59

Albino mutation in animals blocks pigmentation owing to a deficiency in tyrosinase, although it does not affect the differentiation of colorless melanocytes from the neural crest. In the albino Japanese quail (al, sex-linked), it was demonstrated that morphologically normal melanocytes differentiated from neural crest cells in culture and that these cells contained unmelanized melanosomes as expected for the mutant cells. The mutant melanocytes, however, were shown to exhibit tyrosinase activity in the Golgi-endoplasmic reticulum-lysosome region and in the Golgi vesicles. Our results seem to indicate that the mutation at the al locus affects the transport of tyrosinase from the Golgi area to melanosomes.
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PMID:Gene controlling a differentiation step in the quail melanocyte. 313 48

Pigmentation-associated antigen (PAA) or gp75 is a glycoprotein localized to the melanosomes of human melanomas and melanocytes to which a mouse monoclonal antibody (AbTA99) has been produced (T. M. Thomson et al. (1985) J. Invest. Dermatol. 85, 169). Treatment of 3H-labeled immunoprecipitated melanoma PAA with alkaline-borohydride, hydrazinolysis, or N-glycanase released three families of carbohydrate chains (I, II, and III). Peak I consists of a major component (Ia) of sialylated triantennary N-linked chains which are partially substituted with fucose on terminal positions as well as on the chitobiose core and a minor component (Ib) which is a sialylated biantennary N-linked species. Peak II was not well characterized but may be a monoantennary complex chain species. Peak III consists of typical N-linked high mannose units with six to seven mannose residues. Melanocyte PAA carbohydrate chains have the same general features as melanoma PAA except that the biantennary complex chain predominates; this difference resembles that observed between the cell surface glycopeptides of transformed animal cells and their nontransformed counterparts. The glycosylation characteristics of this melanosomal glycoprotein are compared with those of glycoproteins from endoplasmic reticulum, Golgi, and lysosomes, and with tyrosinase. It is suggested that the glycosylation pattern is a reflection of the biosynthetic origin and cellular destination of a particular organelle and its constituents.
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PMID:Glycosylation characteristics of pigmentation-associated antigen (GP75): an intracellular glycoprotein of human melanocytes and malignant melanomas. 353 23

Specific inhibition of core carbohydrate synthesis has been found to induce selective aberration and melanin loss in melanosomes, accompanied by alteration of the carbohydrate moiety in functioning glycoproteins, tyrosinases. In order to further clarify the biologic significance of glycoproteins in the initiation of melanization, initial melanogenesis which occurs during the recovery period following interrupted melanogenesis induced by glycosylation inhibitors, has been electron microscopically investigated. Changes in the tyrosinase activity of the corresponding melanogenic subcellular compartments have also been studied electron cytochemically. Removal of glycosylation inhibition was carried out after exposure of B-16 melanotic melanoma cells to the inhibitors for 10-20 culture days resulting in the loss of their melanization. Recovery of melanization begins visibly 48 h later, thereafter almost attaining the previous normal level by 72 h. At the electron microscopic level, re-formation of melanosomal matrix with periodicity is observed within premelanosomes 48 h after removal of glucosamine, soon followed by deposition of apparent melanin particles along their periodicity by 72 h. In tunicamycin experiments, melanization within premelanosomes starts after the concentration of the fine threadlike interior becomes less distinct followed by a prominence of multiple accumulation of microvesicles within the interior. Electron microscopic dopa reaction shows that the deposition of dopa melanin is prominent in Golgi-associated endoplasmic reticulum of lysosome and coated vesicles up to 24 h after the removal. Thereafter, predominant localization of dopa melanin in premelanosomes gradually increases and finally becomes almost uniform. These observations suggest 2 possible mechanisms for the involvement of glycosylation in melanogenesis: first, the translocation of tyrosinases may be regulated by the presence of specific carbohydrate moieties; second, melanosomal matrix proteins contain carbohydrates which may contribute to the tyrosinase-accepting function or in vivo melanizing function of tyrosinases after forming particle-bound T3 tyrosinase.
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PMID:Importance of glycoproteins in the initiation of melanogenesis: an electron microscopic study of B-16 melanoma cells after release from inhibition of glycosylation. 373 83

The fine structure of integumental erythrophores and the intracellular location of pteridine and carotenoid pigments in adult goldfish, Carassius auratus, were studied by means of cytochemistry, paper and thin-layer chromatography, ionophoresis, density-gradient centrifugal fractionation, and electron microscopy. The ultrastructure of erythrophores is characterized by large numbers of somewhat ellipsoidal pigment granules and a well-developed system of tubules which resembles endoplasmic reticulum. The combined morphological and biochemical approaches show that pteridine pigments of erythrophores are located characteristically in pigment granules and are the primary yellow pigments of these organelles. Accordingly, this organelle is considered to be the "pterinosome" which was originally found in swordtail erythrophores. Major pteridines obtainable from goldfish pterinosomes are sepiapterin, 7-hydroxybiopterin, isoxanthopterin, and 6-carboxyisoxanthopterin. Density-gradient fractions indicate that carotenoids are mostly associated with the endoplasmic reticulum. Both tyrosinase and possibly a tyrosinase inhibitor containing sulfhydryl groups are present in the pterinosome. The possible existence of a tyrosinase inhibitor is suggested by the marked increase of tyrosinase activity upon the addition of iodoacetamide or p-chloromercuribenzoic acid. In the light of their fine structure, pigmentary composition, and enzymatic properties, the erythrophores and pterinosomes are discussed with respect to their probable functions and their relationship to melanophores.
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PMID:Morphological and biochemical characterization of goldfish erythrophores and their pterinosomes. 569 82

We have found that glucosamine (1 mg/ml) or tunicamycin (0.2-0.4 micrograms/ml), specific inhibitors of lipid carrier-dependent glycosylation of protein, when added to cultured B-16 melanoma cells produce a marked loss of pigmentation, accompanied by distinctive biochemical as well as ultrastructural aberrations in their melanogenic compartments. Electron microscopic analysis shows that these newly induced unpigmented cells form uniquely altered melanosomes containing little or no melanin, although their population is not substantially reduced. Within the melanogenic compartments, selective aberration of melanosomes is seen, that is, deformity, bulging, and segregation of their interior membrane, as well as the intramelanosomal formation of irregularly concentric lamellar structure. No apparent structural deformity of Golgi apparatus, Golgi-associated endoplasmic reticulum of lysosome (GERL), and coated vesicles has been observed. Further, no substantial alteration is seen in mitochondria or other cellular structures. Quantitative analysis of altered and nonaltered melanosomes has revealed that the ratio of altered premelanosomes to the total number increases to 44% in glucosamine-treated cells and to 99.5% in tunicamycin-treated cels. Compared to 13% in the control. Electron microscopic dopa reaction has also revealed that these altered melanosomes seem to exhibit a weakly positive or a negative dopa reaction in both glucosamine- and tunicamycin-treated melanoma cells although a number of dopa-positive altered melanosomes are still seen. However, GERL and coated vesicles show no apparent decrease in dopa reaction. It may be concluded that glycoprotein synthesis is integral to the formation of normal melanosomes and to their specific melanizing function, which could be impaired by inhibition of the synthesis of asparagin-linked mannose-containing sugar chains. This results in retrogressive changes in the premelanosomal tyrosinase during its maturation process.
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PMID:Selective aberration and pigment loss in melanosomes of malignant melanoma cells in vitro by glycosylation inhibitors: premelanosomes as glycoprotein. 640 69


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