1,4-Naphthoquinones as inducers of oxidative damage and stress signaling in HaCaT human keratinocytes
1,4-Naphthoquinones as inducers of oxidative damage and stress signaling in HaCaT human keratinocytes
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DOI：
10.1016/j.abb.2010.02.002
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发表时间：
2010-04-15
影响因子：
3.9
通讯作者：
Klotz, Lars-Oliver
中科院分区：
文献类型：
--
作者：
Klaus, Viola;Hartmann, Tobias;Klotz, Lars-Oliver
本文研究了1,4-萘醌、甲萘醌（2-甲基-1,4-萘醌）和天然来源的结构相关醌- 5-羟基萘醌核桃酮、白丹素、2-羟基萘醌劳酮和拉帕醌在人角质形成细胞（HaCaT）中的生物学效应。1,4-萘醌和甲萘醌以及核桃酮和白铅素具有高度的细胞毒性，强烈诱导活性氧（ROS）的形成和耗尽细胞谷胱甘肽。此外，它们诱导氧化DNA碱基损伤和DNA链断裂的积累，正如碱性DNA解绕试验所证明的那样。lawsone和lapachol（高达100 μ M）在这些检测中都没有活性。细胞毒性和氧化作用与应激信号刺激并行：除lawsone和lapachol外，所有测试的醌类均强烈诱导表皮生长因子受体（EGFR）和相关ErbB2受体酪氨酸激酶的磷酸化。水蛭素、核桃酮和甲萘醌的EGFR激活被超氧化物歧化酶模拟物减弱，表明ros相关机制有助于这些萘醌激活EGFR。(C) 2010出版的爱思唯尔公司。
Selected biological effects of 1,4-naphthoquinone, menadione (2-methyl-1,4-naphthoquinone) and structurally related quinones from natural sources - the 5-hydroxy-naphthoquinones juglone, plumbagin and the 2-hydroxy-naphthoquinones lawsone and lapachol - were studied in human keratinocytes (HaCaT). 1,4-naphthoquinone and menadione as well as juglone and plumbagin were highly cytotoxic, strongly induced reactive oxygen species (ROS) formation and depleted cellular glutathione. Moreover, they induced oxidative DNA base damage and accumulation of DNA strand breaks, as demonstrated in an alkaline DNA unwinding assay. Neither lawsone nor lapachol (up to 100 mu M) were active in any of these assays. Cytotoxic and oxidative action was paralleled by stimulation of stress signaling: all tested quinones except lawsone and lapachol strongly induced phosphorylation of the epidermal growth factor receptor (EGFR) and the related ErbB2 receptor tyrosine kinase. EGFR activation by plumbagin, juglone and menadione was attenuated by a superoxide dismutase mimetic, indicating that ROS-related mechanisms contribute to EGFR activation by these naphthoquinones. (C) 2010 Published by Elsevier Inc.