Role of Thiol Compounds in Mammalian Melanin Pigmentation. II. Glutathione and Related Enzymatic Activities

Abstract

Previously, we reported evidence suggesting that, in addition to tyrosinase, glutathione-reductase plays an important role in the regulation and control of the biosynthetic activity of melanocytes. Further investigations were performed on a mammal presenting a well-defined genotype for coat pigmentation, the mutant mouse [subline C57 BL (6J)], namely the nonagouti black (a/a) mutant and the yellow (Ay/a) mutant showing, respectively, pure uniform eumelanin and phaeomelanin pigmentation. Analysis of thiol compounds and glutathione-related enzyme levels in mouse skin gave similar results to those found in tortoise-shell guinea pig skin. The observed differences in the glutathione and glutathione-related enzyme content between black and yellow (or red) skin provide evidence that the increase of glutathione-reductase activity in the environment of the melanocytes may stimulate the pigment cells to produce phaeomelanin instead of eumelanin pigment.

Pink-eyed Dilution Protein Modulates Arsenic Sensitivity and Intracellular Glutathione Metabolism

“…Thiol compounds have been suspected to play a significant role in melanin pigmentation, but the exact mechanisms have remained unknown (Benedetto et al, 1981(Benedetto et al, , 1982Jara et al, 1988;del Marmol et al, 1993;Ito, 1993). Pheomelanin is synthesized from cysteinyl-DOPA building blocks, and the p gene is not transcribed during the pheomelanic phase of the murine agouti hair cycle (Tamate et al, 1989;Rinchik et al, 1993).…”

“…Pheomelanin is synthesized from cysteinyl-DOPA building blocks, and the p gene is not transcribed during the pheomelanic phase of the murine agouti hair cycle (Tamate et al, 1989;Rinchik et al, 1993). Low levels of reduced GSH have been found to be associated with eumelanin production (Benedetto et al, 1981(Benedetto et al, , 1982. Tyrosinase activity is also important in the eumelanin/pheomelanin switch: high tyrosinase activity had been associated with eumelanogenesis and lower tyrosinase activity with pheomelanogenesis (Ito, 1993;Lamoreux et al, 1995).…”

Redox Regulation in Human Melanocytes and Melanoma

“…GSH levels influence melanin synthetic pathways through the formation of adducts with DQ, an unstable intermediate in melanin synthesis produced by tyrosinase action on tyrosine and dopa (7)(8)(9)(10). Like cysteinyldopa, glutathionyldopa formation favors pheomelanin over eumelanin synthesis.…”

Brightness of melanin-based plumage coloration is a cue to oxidative stress in Himalayan Black Bulbuls (Hypsipetes leucocephalus nigerrimus)

“…Glutathione (GSH), another key intracellular antioxidant, has been suggested to inhibit eumelanogenesis and eumelanin-based black ornaments, and might be crucial to the expression of melanin-based traits (Benedetto et al 1982). GSH is a tripeptide thiol found in virtually all animal cells, and often considered as a vital antioxidant.…”