Adaptive downregulation of pheomelanin-related Slc7a11 gene expression by environmentally induced oxidative stress

Pheomelanin is a sulphur-containing yellow-to-reddish pigment whose synthesis consumes the main intracellular antioxidant (glutathione; GSH) and its precursor cysteine. Cysteine used for pheomelanogenesis cannot be used for antioxidant protection. We tested whether the expression of Slc7a11, the gene regulating the transport of cysteine to melanocytes for pheomelanogenesis, is environmentally influenced when cysteine/GSH are most required for antioxidant protection. We found that zebra finches Taeniopygia guttata developing pheomelanin-pigmented feathers during a 12-day exposure to the pro-oxidant diquat dibromide downregulated the expression of Slc7a11 in feather melanocytes, but not the expression of other genes that affect pheomelanogenesis by mechanisms different from cysteine transport such as MC1R and Slc45a2. Accordingly, diquat-treated birds did not suffer increased oxidative stress. This indicates that some animals have evolved an adaptive epigenetic lability that avoids damage derived from pheomelanogenesis. This mechanism should be explored in human Slc7a11 to help combat some cancer types related to cysteine consumption.Financial support was obtained from a Investigador FCT Fellowship (ref. IF/00870/2012/CP0189/CT0009) from the Portuguese Foundation for Science and Technology and by a Ramón y Cajal Fellowship (ref. RYC-2012-10237) from the Spanish Ministry of Economy and Competitiveness (MINECO) to I.G., and from the projects CGL2012-40229-C02-01 and CGL2015-69338-C2-2-P, both from MINECO, to C.A.A.Peer Reviewe