Preprint Article Version 1 This version is not peer-reviewed

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

Version 1 : Received: 5 September 2018 / Approved: 5 September 2018 / Online: 5 September 2018 (08:10:43 CEST)

How to cite: Tanaka, H.; Yamashita, Y.; Umezawa, K.; Hirobe, T.; Ito, S.; Wakamatsu, K. The Pro-Oxidant Activity of Pheomelanin Is Significantly Enhanced by UVA Irradiation: Benzothiazole Moieties Are More Reactive than Benzothiazine Moieties. Preprints 2018, 2018090091 (doi: 10.20944/preprints201809.0091.v1). Tanaka, H.; Yamashita, Y.; Umezawa, K.; Hirobe, T.; Ito, S.; Wakamatsu, K. The Pro-Oxidant Activity of Pheomelanin Is Significantly Enhanced by UVA Irradiation: Benzothiazole Moieties Are More Reactive than Benzothiazine Moieties. Preprints 2018, 2018090091 (doi: 10.20944/preprints201809.0091.v1).

Abstract

It is known 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, the former being transformed to the latter 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) consumption 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.

Subject Areas

pheomelanin; mouse; benzothiazole; benzothiazine; pro-oxidant activity; melanoma; reactive oxygen species; ultraviolet-A; glutathione

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