Regulation of DHICA-mediated antioxidation by dopachrome tautomerase: implication for skin photoprotection against UVA radiation.
Dopachrome tautomerase (Dct) is a critical enzyme in the melanogenesis pathway that isomerizes the intermediate dopachrome to 5,6-dihydroxyindole-2-carboxylic acid (DHICA) and influences the proportion of DHICA monomer incorporated into the 5,6-dihydroxyindole (DHI) polymer in eumelanin. To investigate whether Dct inactivation affects skin photoprotection against ultraviolet radiation, we examined levels of reactive oxygen species (ROS), sunburn cell formation, epidermal cell apoptosis, and melanin composition in skins of Dct(-/-) knockout mice compared with skins of wild-type C57BL/6 mice under UVA-induced oxidative stress. The results demonstrate that Dct inactivation elevates the level of ROS, increases the numbers of sunburn cells and apoptotic cells, and decreases the amount of eumelanin in the epidermis upon exposure to chronic UVA radiation. Moreover, we determined the effects of DHICA-melanin, DHI-melanin, and a mixture of both on hydroxyl radical generation in the Fenton reaction utilizing an electron spin resonance assay. DHICA-melanin exhibits a potent hydroxyl radical-scavenging activity, whereas DHI-melanin does not. Thus, this study suggests that DHICA monomers are required to incorporate into the DHI polymer backbone of eumelanin, which highlights the important role of Dct in the regulation of DHICA-mediated antioxidation.
Jiang
Shan
S
Department of Dermatology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Liu
Xiao-Ming
XM
Dai
Xin
X
Zhou
Qiong
Q
Lei
Tie-Chi
TC
Beermann
Friedrich
F
Wakamatsu
Kazumasa
K
Xu
Shi-Zheng
SZ
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D017209:Apoptosis / Q000528:radiation effects; D020287:In Situ Nick-End Labeling; D007211:Indoles / Q000378:metabolism*; D019746:Intramolecular Oxidoreductases / Q000378:metabolism*; D008543:Melanins / Q000378:metabolism / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011836:Radiation Tolerance / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000528:radiation effects; D012867:Skin / Q000378:metabolism* / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects
D000975:Antioxidants; D007211:Indoles; D008543:Melanins; D017382:Reactive Oxygen Species; C041877:eumelanin; C030692:5,6-dihydroxy-2-indolylcarboxylic acid; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase