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)

A high percentage of the total tyrosinase found in Harding-Passey mouse melanoma occurs as a soluble form. This paper shows that melanosomal tyrosinase can be solubilized by several endogenous proteases to yield active tyrosinase. This enzyme, once proteolytically solubilized, can be further degraded, leading to enzyme inactivation. The nature and specificity of the main proteases involved in the solubilization process change depending on the size and necrosis stage of the tumour. Cathepsin B could be the main protease responsible for the solubilization in small tumours (less than 0.5 g). Large tumours are rich in necrotic cells, and cathepsin D and serine-proteases are the main hydrolytic enzymes involved in the proteolytic action on melanosomes. These results support the view that the high activity of tyrosinase found in the soluble fraction of malignant melanoma is mainly an artefact resulting from degradation of melanosomes by a variety of endogenous proteases, rather than the result of the actual occurrence of high levels of an independent cytosolic isozyme.
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PMID:Action of endogenous proteases on the distribution of tyrosinase isozymes in Harding-Passey mouse melanoma. 250 24

The biosynthesis, structure, and topology of a melanoma-associated antigen, previously defined with the monoclonal antibody NKI/C-3 was studied. A polyclonal rabbit antiserum was raised against the antigen with a broader reactivity than the previously used monoclonal antibody NKI/C-3. The antigen was shown to consist of a single protein backbone to which two or three N-linked glycans were added cotranslationally. Extensive further heterogeneity was generated in the Golgi compartment and was shown to be dependent on the presence of complex type sugars. Although the antigen is associated with melanomas, it was not codistributed with the tyrosinase activity associated with melanogenesis. The antigen did show codistribution with cathepsin D, which is a marker for lysosomal functions.
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PMID:Structural heterogeneity of a human melanoma-associated antigen. 264 40

Melanomas exhibiting mutated ras genes are frequently invasive and amelanotic. Transfecting melanocytes with ras oncogenes causes transformation and a loss of visible pigmentation. We analyzed murine melanocytes rendered amelanotic by transfection with the v-rasHa oncogene. Consistent with previous reports, tyrosinase and tyrosinase-related protein-1 (TRP-1) were not expressed by transformed cells. In addition, lack of expression of TRP-2 and the product of the silver locus was documented. Levels of melanosomal matrix antigens, the pink-eyed dilution locus protein and lysosome-associated membrane protein-1 were markedly reduced. Residual matrix antigens were localized by immunofluorescence to large vacuoles distributed peri-nuclearly in transfected cells. Electron microscopy demonstrated the absence of typical melanosomes and the presence of large vacuolar structures, also in a peri-nuclear distribution. Although levels of lysosomal hydrolases, such as beta-glucuronidase and cathepsin D, were diminished, marked elevations were observed in the expression of cathepsins B and L, 2 thiol proteases implicated in the acquisition of invasiveness. Our data demonstrate that transfection of melanocytes with v-rasHa is sufficient to disrupt the biogenesis of melanosomes and to up-regulate thiol protease synthesis, providing insights into the amelanotic and invasive nature of melanomas exhibiting mutations in ras genes.
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PMID:Melanosomal and lysosomal alterations in murine melanocytes following transfection with the v-rasHa oncogene. 863 74

The hair follicles exhibit an intrinsic hair cycle that is divided into three phases; growth (anagen), transition (catagen) and quiescence (telogen). To make sure of the effects on hair growth by chemical substances, we should evaluate the induction of the anagen phase and/or elongation of the anagen period and delay in catagen separately, but the regulatory mechanism of the hair cycle is unclear. We have investigated the levels of biochemical markers in the third hair cycle period of C3H mouse (8 weeks, male) after depilation and compared them with those in a non-treated group. The dorsal areas (2 cm x 4 cm) were clipped and depilated with hair remover. The dorsal skin samples were collected 1, 8, 11, 15 and 18 days after depilation and the levels of biochemical markers, i.e. skin transglutaminase, skin sulfhydryl oxidase, cathepsin D, gamma-glutamyl transpeptidase, alkaline phosphatase, acid phosphatase, tyrosinase activities and histamine content in each skin sample were examined. The levels of gamma-glutamyl transpeptidase, tyrosinase and alkaline phosphatase were relevant to hair re-growth in the control group, but not skin transglutaminase, skin sulfhydryl oxidase, cathepsin D activities. The histamine content increased just after depilation treatment and returned to the normal level within two weeks, compared with the non-treated group. All these results suggest that the markers examined in this C3H mice model are useful for studying the distinctive process of hair re-growth caused by active substances.
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PMID:Evaluation of biochemical indices as a hair cycle marker in C3H mice. 884 Jan 42

Pathways of melanosome biogenesis in retinal pigment epithelial (RPE) cells have received less attention than those of skin melanocytes. Although the bulk of melanin synthesis in RPE cells occurs embryonically, it is not clear whether adult RPE cells continue to produce melanosomes. Here, we show that progression from pmel17-positive premelanosomes to tyrosinase-positive mature melanosomes in the RPE is largely complete before birth. Loss of functional Rab38 in the "chocolate" (cht) mouse causes dramatically reduced numbers of melanosomes in adult RPE, in contrast to the mild phenotype previously shown in skin melanocytes. Choroidal melanocytes in cht mice also have reduced melanosome numbers, but a continuing low level of melanosome biogenesis gradually overcomes the defect, unlike in the RPE. Partial compensation by Rab32 that occurs in skin melanocytes is less effective in the RPE, presumably because of the short time window for melanosome biogenesis. In cht RPE, premelanosomes form but delivery of tyrosinase is impaired. Premelanosomes that fail to deposit melanin are unstable in both cht and tyrosinase-deficient RPE. Together with the high levels of cathepsin D in immature melanosomes of the RPE, our results suggest that melanin deposition may protect the maturing melanosome from the activity of lumenal acid hydrolases.
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PMID:Melanosome maturation defect in Rab38-deficient retinal pigment epithelium results in instability of immature melanosomes during transient melanogenesis. 1767 Nov 65

Preliminary mechanism of acidic electrolyzed water (AEW) ice on improving the quality and safety of shrimp was investigated by examining the physicochemical and microbiological changes, sarcoplasmic proteins and enzymatic activities. The results showed that compared with tap water (TW) ice, AEW ice had an obvious (p<0.05) capability in limiting the changes of pH and shrinkage of muscle fibers in shrimp. Plate count enumeration and PCR-DGGE indicated that AEW greatly inhibited growth of bacteria on shrimp. Additionally, AEW ice had no adverse effects on sarcoplasmic proteins by SDS-PAGE method. And AEW ice displayed inhibitory activity (p<0.05) toward cathepsin B and polyphenol oxidase (PPO), although it did not present positive effects on inhibiting cathepsin D, acid phosphatase and lipase activity. Thus, this study brought new evidence to further demonstrate that AEW ice can serve as a promising technology for improving the quality of aquatic products in food industry.
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PMID:Preliminary mechanism of acidic electrolyzed water ice on improving the quality and safety of shrimp. 2562 41

Melanin metabolism disorders may cause severe impacts on the psychological and social activities of patients. Different from the other two steps of melanin metabolism, namely synthesis and transport, little has been known about the mechanism of melanin degradation. Isoimperatorin (ISO) suppressed the activity of tyrosinase, an essential enzyme in melanin biosynthesis, hence, we investigated the effects and mechanism of ISO in melanin reduction. ISO stimulation significantly reduces the melanin contents and PMEL 17 protein levels; meanwhile, the activity and the protein levels of two critical lysosomal enzymes, Cathepsin B and Cathepsin D, can be significantly increased by ISO treatment. MiR-3619 inhibited the expression of CSTB and CSTD, therefore affecting ISO-induced degradation of melanin. In summary, ISO reduces the melanin content via miR-3619/CSTB and miR-3619/CSTD axes. ISO could be a potent skin-whitening agent, which needs further in vivo and clinical investigation.
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PMID:Isoimperatorin (ISO) reduces melanin content in keratinocytes via miR-3619/CSTB and miR-3619/CSTD axes. 3229 3