Biological effects of menadione photochemistry: effects of menadione on biological systems may not involve classical oxidant production.
Biological effects of menadione photochemistry: effects of menadione on biological systems may not involve classical oxidant production.
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DOI：
10.1042/0264-6021:3500797
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发表时间：
2000-09
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影响因子：
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通讯作者：
M. McCormick;G. Denning;K. Reszka;P. Bilski;G. Buettner;G. T. Rasmussen;M. A. Railsback;B. Britigan
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文献类型：
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作者：
M. McCormick;G. Denning;K. Reszka;P. Bilski;G. Buettner;G. T. Rasmussen;M. A. Railsback;B. Britigan
由于细胞介导的甲萘醌还原会导致活性氧簇（ROS）的产生，因此这种醌被广泛用于研究活性氧簇对细胞功能的影响。我们报告了甲萘醌暴露于A549人肺上皮细胞后，细胞内钙离子（[Ca（2+）]（i））和ROS形成均呈剂量依赖性增加。引发这两种事件所需的甲萘醌浓度明显不同，ROS检测需要更高水平的甲萘醌。抗氧化防御的调节剂（例如丁硫丙磺酰亚胺、3-氨基-1，2，4-三唑）对甲萘醌引起的[Ca（2+）]（i）反应几乎没有影响，这表明ROS的形成不能解释甲萘醌依赖的[Ca（2+）]（i）改变。其他证据表明，甲萘醌光化学可能是负责观察到的[Ca（2+）]（i）的影响。具体而言：（a）用自旋捕获剂5，5-二甲基-1-吡咯啉-N-氧化物（DMPO）进行的EPR研究表明，光暴露（在340 nm处的最大效应）刺激DMPO/（.）OH自旋加合物对抗氧化剂干预不敏感;（B）DMPO抑制甲萘醌和[Ca（2+）]（i）的光依赖性增加;和（c）光（在340 nm处的最大效应）增强甲萘醌对细胞活力的有害作用，如通过（51）Cr释放所确定的。这些光效应似乎不涉及甲萘醌形成单线态氧，而是甲萘醌在三重态引发的氧化化学反应的结果。这项工作表明，光照射产生的甲萘醌物质可以对细胞功能产生生物学效应，并指出光化学在甲萘醌介导的细胞损伤研究中的潜在重要性。
Because cell-mediated reduction of menadione leads to the generation of reactive oxygen species (ROS), this quinone is widely used to investigate the effects of ROS on cellular functions. We report that A549 human lung epithelial cells exposed to menadione demonstrate a dose-dependent increase in both intracellular calcium ([Ca(2+)](i)) and ROS formation. The concentrations of menadione required to initiate these two events are markedly different, with ROS detection requiring higher levels of menadione. Modulators of antioxidant defences (e.g. buthionine sulphoximine, 3-amino-1,2,4-triazole) have little effect on the [Ca(2+)](i) response to menadione, suggesting that ROS formation does not account for menadione-dependent alterations in [Ca(2+)](i). Additional evidence suggests that menadione photochemistry may be responsible for the observed [Ca(2+)](i) effects. Specifically: (a) EPR studies with the spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) show that light exposure (maximum effect at 340 nm) stimulates menadione-dependent formation of the DMPO/(.)OH spin adduct that was not sensitive to antioxidant interventions; (b) DMPO inhibits menadione and light-dependent increases in [Ca(2+)](i); and (c) light (maximum effect at 340 nm) augments the deleterious effects of menadione on cell viability as determined by (51)Cr release. These photo effects do not appear to involve formation of singlet oxygen by menadione, but rather are the result of the oxidizing chemistry initiated by menadione in the triplet state. This work demonstrates that menadione species generated by photo-irradiation can exert biological effects on cellular functions and points to the potential importance of photochemistry in studies of menadione-mediated cell damage.