DUAL ROLE OF MELANINS AND MELANIN PRECURSORS AS PHOTOPROTECTIVE AND PHOTOTOXIC AGENTS - INHIBITION OF ULTRAVIOLET RADIATION-INDUCED LIPID-PEROXIDATION

DUAL ROLE OF MELANINS AND MELANIN PRECURSORS AS PHOTOPROTECTIVE AND PHOTOTOXIC AGENTS - INHIBITION OF ULTRAVIOLET RADIATION-INDUCED LIPID-PEROXIDATION
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DOI:
10.1111/j.1751-1097.1995.tb09883.x
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发表时间:
1995-06-01
影响因子:
3.3
通讯作者:
JIMBOW, K
JIMBOW, K
中科院分区:
生物学3区
文献类型:
--
作者:
SCHMITZ, S;THOMAS, PD;JIMBOW, K

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紫外线辐射(UVR)是皮肤癌的危险因素之一,也是黑色素沉着的主要诱因,而黑色素沉着是哺乳动物皮肤抗辐射损伤的主要保护机制。黑色素,真黑素和泛黑素,在抵御紫外线辐射方面可能很重要,但它们的前体通常被认为是光毒性的。现有资料表明DNA损伤是光毒性的机制。然而,黑色素前体通过脂质过氧化作用对膜损伤的影响是另一个重要的,可能更相关的(从这些分子的黑素体限制的角度来看)光毒性机制,目前尚不清楚。作为uvr -黑色素-膜相互作用的模型系统。我们在真黑素、褐黑素及其两种主要前体5,6-二羟基吲哚(DHI)和5- s -半胱氨酸多巴(SCD)存在的情况下照射脂质体,这两种黑色素前体的存在大大减少了UVR暴露导致的脂质过氧化产物的形成,黑色素前体的抗氧化活性在强氧化剂条件下(Fe3+存在)减弱。这些结果表明,黑色素前体可能在保护皮肤免受紫外线辐射的有害影响(包括光致癌作用)方面发挥重要作用。
Ultraviolet radiation (UVR) is one of the risk factors for skin cancer and the main inducer of melanin pigmentation, the major protective mechanism of mammalian skin against radiation damage. The melanin pigments, eumelanin and pheomelanin, are likely to be important in protection against UVR, but their precursors are generally considered as phototoxic. The available data suggest DNA damage as the mechanism of phototoxicity. However, the effect of melanin precursors on membrane damage through lipid peroxidation, another important and probably more relevant (from the point-of-view of the melanosomal confinement of these molecules) mechanism of phototoxicity, is net known. As a model system for UVR-melanin-membrane interactions. we irradiated liposomes in the presence of eumelanin, pheomelanin and two of their major precursors, 5,6-dihydroxyindole (DHI) and 5-S-cysteinyldopa (SCD), The presence of the two melanin precursors substantially reduced the formation of lipid peroxidation products resulting from UVR exposure, The antioxidant activity of the melanin precursors was diminished under strong prooxidant conditions (presence of Fe3+). These results suggest that melanin precursors may have an important role in the protection of skin against the harmful effects of UVR including photocarcinogenesis.