title: Dopachrome tautomerase decreases the binding of indolic melanogenesis intermediates to proteins.
abstract: Dopachrome tautomerase (DCT) is a recently characterized enzyme contributing to the control of melanogenesis in mammals. The enzyme catalyzes the rearrangement of L-Dopachrome (L-DC) to 5,6-dihydroxyindole 2-carboxylic acid (DHICA), while the spontaneous rearrangement of L-DC leads to 5,6-dihydroxyindole (DHI). Due to the lower reactivity of DHICA in comparison to DHI, DCT could provide a protective mechanism against the cytotoxicity of decarboxylated indolic melanogenic intermediates by limiting the formation of these highly reactive decarboxylated species within melanocytes. We have followed the binding of radioactive melanogenic precursors to a model protein, bovine serum albumin (BSA). Using L-DC as initial melanin precursor, this binding was decreased by DCT in a concentration-dependent manner. In the presence of tyrosinase, the binding of L-Dopa-derived intermediates to BSA was also decreased by DCT and the percentage of decrease was even higher than using L-DC as initial melanin precursor. SDS-PAGE followed by fluorographic detection of radioactive bands showed the formation of covalent adducts between BSA and melanin precursors, as well as of aggregated forms of this protein. This aggregation was also diminished by DCT. These data indicate that DCT could play a protective role against the cytotoxic action of decarboxylated indoles within mammalian melanocytes.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine, University of Murcia, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Salinas
authors.forename: J C
authors.initials: JC
authors.lastname: García-Borrón
authors.forename: F
authors.initials: F
authors.lastname: Solano
authors.forename: J A
authors.initials: JA
authors.lastname: Lozano
mesh_terms: D000818:Animals; D007211:Indoles / Q000378:metabolism*; D019746:Intramolecular Oxidoreductases; D007535:Isomerases / Q000378:metabolism*; D008543:Melanins / Q000096:biosynthesis*; D008544:Melanocytes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011498:Protein Precursors / Q000378:metabolism*; D011809:Quinones / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000378:metabolism*
chemical_list: D007211:Indoles; D008543:Melanins; D011498:Protein Precursors; D011809:Quinones; D012710:Serum Albumin, Bovine; D007535:Isomerases; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase