Enzymatic control of pigmentation in mammals

Abstract

Visible pigmentation in mammals results from the synthesis and distribution of melanin in the skin, hair bulbs, and eyes. The melanins are produced in melanocytes and can be of two basic types: eumelanins, which are brown or black, and phaseomelanins, which are red or yellow. In mammals typically there are mixtures of both types. The most essential enzyme in this melanin biosynthetic pathway is tyrosinase and it is the only enzyme absolutely required for melanin production. However, recent studies have shown that mammalian melanogenesis is not regulated solely by tyrosinase at the enzymatic level, and have identified additional melanogenic factors that can modulate pigmentation in either a positive or negative fashion. In addition, other pigment-specific genes that are related to tyrosinase have been cloned which encode proteins that apparently work together at the catalytic level to specify the quantity and quality of the melanins synthesized. Future research should provide a greater understanding of the enzymatic interactions, processing, and tissue specificity that are important to pigmentation in mammals.

Antimelanogenic Activity of 3,4-Dihydroxyacetophenone: Inhibition of Tyrosinase and MITF

“…8) Twenty ml mushroom tyrosinase (1,000 units) was added to a 96-well microplate, which was incubated at 25 C for 30 min. The amount of dopachrome produced in the reaction mixture was determined spectrophotometrically at 492 nm.…”

MIA (melanoma inhibitory activity) promoter mediated tissue-specific suicide gene therapy of malignant melanoma

“…20,21,24,25 This promoter is almost exclusively active in melanocytes and in most but not all human melanomas. 46 In contrast, hMIA promoter activity correlates with melanoma progression. 28,47 Therefore, the MIA promoter may confer melanoma-restricted expression of the suicide gene also in advanced stages of the disease.…”

Metastatic potential of human melanoma cells in nude mice - characterisation of phenotype, cytokine secretion and tumour-associated antigens

“…injected human melanoma cells (Singh et al, 1994). Furthermore, the expression of melanosomal proteins, often considered to be differentiation markers (Hearing and Tsukamoto, 1991), and the capacity for metastasis formation in nude mice were not linked.…”

“…Primer sequences were devised according to the published sequence for human tyrosinase (Smith et al, 1991), for MAGE-1 ( Van der Bruggen et al, 1991), for MAGE-3 (Gaugler et al, 1994), for TRP-1 (Shibata et al, 1992), for TRP-2 (Bouchard et al, 1994), for gplOO (Kwon et al, 1991;Wagner et al, 1995) and for MELAN-A/MART-1 (Coulie et al, 1994;Kawakami et al, 1994). The following primers were used: Tyr-l: TTG GCA GAT TGT CTG TAG CC and Tyr-2: AGG CAT TGT GCA TGC TGC TT (Hearing and Tsukamoto, 1991 Tyrosine hydroxylase assay Tyrosine hydroxylase activity was measured by monitoring conversion of L-[3H]tyrosine to L-dopa and the production of 3H20 as described (Artuc et al, 1995). Cell extracts (50 ig of protein) were incubated in 50 ,ul of a reaction mixture containing 0.25 mM L-tyrosine, 5 ,iCi ml-1 [3H]tyrosine and 0.05 mM L-dopa in 0.1 M phosphate buffer (pH 6.8) for 2 h at 37°C.…”