7-Dehydrocholesterol enhances ultraviolet A-induced oxidative stress in keratinocytes: roles of NADPH oxidase, mitochondria, and lipid rafts.
7-Dehydrocholesterol enhances ultraviolet A-induced oxidative stress in keratinocytes: roles of NADPH oxidase, mitochondria, and lipid rafts.
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DOI：
10.1016/j.freeradbiomed.2006.09.006
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发表时间：
2006-12
影响因子：
7.4
通讯作者：
A. Valencia;Anpuchchelvi Rajadurai;A. B. Carle;I. Kochevar
中科院分区：
文献类型：
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作者：
A. Valencia;Anpuchchelvi Rajadurai;A. B. Carle;I. Kochevar
长波太阳UVA辐射刺激活性氧（ROS）和前列腺素E2（PGE2）的形成，参与皮肤光敏和肿瘤促进。高水平的7-脱氢胆固醇（7-DHC），胆固醇的前体，导致史密斯-莱姆利-奥皮茨综合征（SLOS）患者对UVA的过度光敏。角化细胞用7-DHC部分替代胆固醇，迅速（<5分钟）增加uva诱导的ROS、细胞内钙、磷脂酶a2活性、PGE2和NADPH氧化酶活性。在这些细胞中，uva诱导的ROS和pge2的产生通过使用siRNA或使用线粒体自由基猝灭剂MitoQ来消耗NADPH氧化酶的Nox1亚基来抑制。用7-DHC部分替代胆固醇也会破坏膜脂筏结构域，尽管胆固醇的消耗也会破坏脂筏，但不会影响uva诱导的ROS和PGE2的增加。含有7-DHC的磷脂脂质体比含有胆固醇的磷脂脂质体更容易被自由基氧化。这些结果表明，7-DHC通过增强自由基介导的膜脂氧化来促进UVA诱导的快速ROS和pge2的形成，这一机制可能是SLOS中UVA光敏性的基础。
Long wavelength solar UVA radiation stimulates formation of reactive oxygen species (ROS) and prostaglandin E2(PGE2), which are involved in skin photosensitivity and tumor promotion. High levels of 7-dehydrocholesterol (7-DHC), the precursor to cholesterol, cause exaggerated photosensitivity to UVA in patients with Smith-Lemli-Opitz syndrome (SLOS). Partially replacing cholesterol with 7-DHC in keratinocytes rapidly (<5 min) increased UVA-induced ROS, intracellular calcium, phospholipase A2activity, PGE2, and NADPH oxidase activity. UVA-induced ROS and PGE2production were inhibited in these cells by depleting the Nox1 subunit of NADPH oxidase using siRNA or using a mitochondrial radical quencher, MitoQ. Partial replacement of cholesterol with 7-DHC also disrupted membrane lipid raft domains, although depletion of cholesterol, which also disrupts lipid rafts, did not affect UVA-induced increases in ROS and PGE2. Phospholipid liposomes containing 7-DHC were more rapidly oxidized by a free radical mechanism than those containing cholesterol. These results indicate that 7-DHC enhances rapid UVA-induced ROS and PGE2formation by enhancing free radical-mediated membrane lipid oxidation and suggests that this mechanism might underlie the UVA photosensitivity in SLOS.