Disease relevance of Dopachrome

• Radiation resistance of human melanoma analysed by retroviral insertional mutagenesis reveals a possible role for dopachrome tautomerase [1].
• Dopachrome conversion factor, purified from Cloudman S91 melanoma cells, converts dopachrome, which is orange, to a colorless compound [2].
• Drosophila yellow -y gene and yellow -b, -c, -f and -f2 genes were expressed in an insect cell/baculovirus expression system and their corresponding recombinant proteins were screened for dopachrome-conversion enzyme activity [3].
• Expression of tyrosinase-related protein 2/DOPAchrome tautomerase in the retinoblastoma [4].
• Cloning and characterization of a dopachrome conversion enzyme from the yellow fever mosquito, Aedes aegypti [5].

High impact information on Dopachrome

• DOPAchrome tautomerase is one such melanogenic enzyme that isomerizes the pigmented intermediate DOPAchrome to DHICA (5,6-dihydroxyindole-2-carboxylic acid) rather than to DHI (5,6-dihydroxyindole), which would be generated spontaneously [6].
• TRP-2 is the much sought melanogenic enzyme DOPAchrome tautomerase (DT), which catalyses the conversion of DOPAchrome to 5,6,dihydroxyindole-2-carboxylic acid [7].
• These data indicate that the binding site for S-hexylglutathione is the same as the catalytic site for the dopachrome tautomerase activity of MIF [8].
• Therefore, aromatization of dopachrome seems to accompany its decarboxylation as well [9].
• Addition of the two epidermal cytokines, tumor necrosis factor-alpha or interleukin-1 alpha, to cultures of human melanocytes from different skin types caused decreased proliferation, tyrosinase activity and expression of tyrosinase, tyrosinase-related protein-1 and DOPAchrome tautomerase [10].

Chemical compound and disease context of Dopachrome

• Effect of amphotericin B on dopachrome tautomerase activity and other melanogenic parameters in cultured B16/F10 melanoma cells [11].
• Peroxidase, isolated from B16 mouse melanoma, converted tyrosine to dopachrome in the presence of either dopa or dihydroxyfumarate co-factor [12].

Biological context of Dopachrome

• Cloning of the human DOPAchrome tautomerase/tyrosinase-related protein 2 gene and identification of two regulatory regions required for its pigment cell-specific expression [13].
• Cell-density-dependent regulation of expression and glycosylation of dopachrome tautomerase/tyrosinase-related protein-2 [14].
• These data show that the human tyrosinase-related protein-2/DOPAchrome tautomerase gene can yield different isoforms by alternative poly(A) site usage or by alternative splicing [15].
• A resolved first-order rate constant of 249 s-1 is evaluated for the cyclization of the basic form of dopaquinone that leads to dopachrome as a product with strong absorption bands at 305 and 485 nm [16].
• In order to eliminate false results caused by tyrosinase inhibition, which also will decrease the dopachrome concentration, the oxygen consumption was followed potentiometrically [17].

Anatomical context of Dopachrome

• Tyrosinase activity and the quantities of tyrosinase enzyme, tyrosinase-related protein-1 and DOPAchrome tautomerase gradually increased with increased melanin content and Percoll density of the isolated melanocyte subpopulations [10].
• 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 [18].
• T1, T2, and T2 contain blocking factor activity, while isozyme T4, the major tyrosinase species found in melanosomes, contains activity that accelerates melanin formation from dopachrome [19].
• Detection of dopachrome isomerase on gels and membranes [20].
• The SHK-1 cells expressed transcripts specific for a mammalian CD83 homologue, a standard surface marker for activated or differentiated dendritic cells, and dopachrome tautomerase/tyrosinase-related protein-2, a melanocyte specific enzyme essential for melanin production [21].

Associations of Dopachrome with other chemical compounds

• It is shown that dopachrome (2-carboxy-2,3-dihydroindole-5,6-quinone) tautomerase (DCT) is a glycoprotein containing N-linked oligosaccharides [22].
• The basal synthesis of melanin and the activity levels of tyrosine hydroxylase, dihydroxyphenylalanine (DOPA) oxidase, or DOPAchrome tautomerase were comparable to control Caucasian melanocytes in culture [23].
• Dopamine was shown by mass spectroscopy to be oxidized to decarboxy dopachrome, an intermediate of melanin synthesis [24].
• Effect of penicillamine on the conversion of dopa to dopachrome in the presence of tyrosinase or ceruloplasmin [25].
• In the absence of tyrosine or dopa, tyrosinase did not oxidize 6-tetrahydrobiopterin, suggesting that a reaction intermediate between dopa and dopachrome was a target for the inhibition [26].

Gene context of Dopachrome

• Other factors also may influence melanogenesis and a unique melanogenic inhibitor suppresses tyrosinase and DOPAchrome tautomerase activities, but does not affect the spontaneous rate of DOPAchrome decarboxylation to DHI [27].
• For proper melanin production, several specific enzymes such as tyrosinase, tyrosinase-related protein 1 (TRP-1) and dopachrome tautomerase are required [28].
• Identification of Drosophila melanogaster yellow-f and yellow-f2 proteins as dopachrome-conversion enzymes [3].
• Dynamic regulation of the human dopachrome tautomerase promoter by MITF, ER-alpha and chromatin remodelers during proliferation and senescence of human melanocytes [29].
• This heterogeneity may be attributed to differences in the activity and expression of the three melanogenic proteins: tyrosinase and tyrosinase-related proteins 1 and 2 (gp75 and DOPAchrome tautomerase, respectively), which in turn are affected by certain regulatory factors [10].

Analytical, diagnostic and therapeutic context of Dopachrome

• This procedure is more sensitive than silver staining for detection of dopachrome isomerase and as little as 15 ng of purified protein could be easily detected on gels [30].
• The inhibition study with dihydroxyphenylalanine (DOPA) as substrate is based on separation of the enzymatic reaction components by reversed phase HPLC and the UV detection of the dopachrome formed [31].

References