Reverse Engineering Applied to Red Human Hair Pheomelanin Reveals Redox-Buffering as a Pro-Oxidant Mechanism.

Eunkyoung Kim,Lucia Panzella,Gregory F Payne,Alessandra Napolitano,William E Bentley,Raffaella Micillo

doi:10.1038/srep18447

Eunkyoung Kim, Lucia Panzella + Show 4 more

Open Access

https://doi.org/10.1038/srep18447

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Abstract

Pheomelanin has been implicated in the increased susceptibility to UV-induced melanoma for people with light skin and red hair. Recent studies identified a UV-independent pathway to melanoma carcinogenesis and implicated pheomelanin’s pro-oxidant properties that act through the generation of reactive oxygen species and/or the depletion of cellular antioxidants. Here, we applied an electrochemically-based reverse engineering methodology to compare the redox properties of human hair pheomelanin with model synthetic pigments and natural eumelanin. This methodology exposes the insoluble melanin samples to complex potential (voltage) inputs and measures output response characteristics to assess redox activities. The results demonstrate that both eumelanin and pheomelanin are redox-active, they can rapidly (sec-min) and repeatedly redox-cycle between oxidized and reduced states, and pheomelanin possesses a more oxidative redox potential. This study suggests that pheomelanin’s redox-based pro-oxidant activity may contribute to sustaining a chronic oxidative stress condition through a redox-buffering mechanism.

Highlights

The challenge in understanding melanin function is that these pigments are structurally complex and there are comparatively few characterization methods available
The synthetic melanins were prepared by enzymatic oxidation of dihydroxyphenylalanine and 5-S-cysteinyldopa the main biosynthetic precursors of natural eumelanin and pheomelanin, respectively
Natural melanin samples were purified from human hair by enzymatic proteolytic procedures[9]

Summary

Introduction

The challenge in understanding melanin function is that these pigments are structurally complex and there are comparatively few characterization methods available. The measured output currents are analyzed to assess the redox activities of the entrapped melanin[23,24] In essence, this reverse engineering approach aims to characterize the redox-properties of the melanin by exposing the sample to controlled redox perturbations and analyzing the output response characteristics. We first apply this experimental reverse engineering approach to compare the redox properties of pheomelanin and eumelanin using model synthetic pigments prepared by oxidation of the biosynthetic precursors under physiologically relevant conditions. We observe that both model melanins are redox-active and can engage in oxidative and reductive redox-cycling reactions. We suggest a redox buffering mechanism may explain pheomelanin’s pro-oxidative activities

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