The Pro-Oxidant Activity of Pheomelanin is Significantly Enhanced by UVA Irradiation: Benzothiazole Moieties Are More Reactive than Benzothiazine Moieties.

Hitomi Tanaka,Yui Yamashita,Kana Umezawa,Tomohisa Hirobe,Kazumasa Wakamatsu,Shosuke Ito

doi:10.3390/ijms19102889

Hitomi Tanaka, Yui Yamashita + Show 4 more

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https://doi.org/10.3390/ijms19102889

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Abstract

It is generally considered that eumelanin (EM) is photoprotective while pheomelanin (PM) is phototoxic. A recent study using a mouse model demonstrated that PM produces reactive oxygen species (ROS) that cause DNA damage and eventually lead to melanomagenesis. A biochemical study showed that PM possesses a pro-oxidant activity. PM consists of benzothiazine (BT) and benzothiazole (BZ) moieties, BT moieties being transformed to BZ moieties by heat or light. In this study, we compared the effects of ultraviolet A (UVA) irradiation using synthetic PMs with different BT to BZ ratios and using various coat color mouse hairs. We found that UVA irradiation of BZ-PM increased glutathione (GSH) depletion and generated more H2O2 than UVA irradiation of BT-PM. Non-irradiated controls did not exhibit strong pro-oxidant activities. Upon UVA irradiation, yellow mouse hairs oxidized GSH and produced H2O2 faster than black or albino mouse hairs. Next, to examine the mechanism of the pro-oxidant activity of BT-PM and BZ-PM, we examined the pro-oxidant activities of 7-(2-amino-2-carboxyethyl)-dihydro-1,4-benzothiazine-3-carboxylic acid (DHBTCA) and 6-(2-amino-2-carboxyethyl)-4-hydroxybenzothiazole (BZ-AA) as BT and BZ monomers, respectively. Their pro-oxidant activities were similar, but a large difference was seen in the effects of ROS scavengers, which suggests that the redox reactions may proceed via singlet oxygen in BZ-AA and via superoxide anions in DHBTCA. These results show that UVA enhances the pro-oxidant activity of PM, in particular BZ-PM.

Highlights

Melanoma is a malignant skin tumor that arises from melanocytes
We recently examined the photoreactivity. These results showed that in the short wavelength part of ultraviolet A (UVA) (320–360 nm), the photogeneration efficiency of singlet oxygen is higher for synthetic pheomelanins than for DHICA-melanin and DOPA-melanin
We considered that the excitation of different melanin chromophores is responsible for the photogeneration of singlet oxygen in the wavelength range

Summary

Introduction

Melanoma is a malignant skin tumor that arises from melanocytes. The incidence of melanoma is increasing worldwide every year, especially in subjects with fair skin and light-colored hair [1]. A recent study by Fajuyigbe et al examined the DNA protection factors (DNA-PFs) of constitutive melanin by comparing fair skin with dark skin and showed that the DNA-PF of melanin is dependent on its epidermal localization and comparable to the differences in keratinocyte carcinoma incidence between light and black skin types [9]. The ultraviolet (UV) portion of sunlight that reaches the earth’s surface is comprised of UVA (ultraviolet A) (320–400 nm) and UVB (290–320 nm). Both UVA and UVB lead to tanning of human skin following sun exposure. UVB promotes pigmentation that is photoprotective, whereas UVA induces photooxidation of preexisting melanin pigments that may not be photoprotective [17,18]

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