Iron deficiency aggravates DMNQ-induced cytotoxicity via redox cycling in kidney-derived cells
Iron deficiency aggravates DMNQ-induced cytotoxicity via redox cycling in kidney-derived cells
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缺铁通过肾源性细胞中的氧化还原循环加重 DMNQ 诱导的细胞毒性
DOI：
10.1080/10715762.2022.2154668
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发表时间：
2022
影响因子：
3.3
通讯作者：
Suzuki Keiichiro
中科院分区：
文献类型：
--
作者：
Yoshihara Daisaku;Fujiwara Noriko;Eguchi Hironobu;Sakiyama Haruhiko;Suzuki Keiichiro
铁是大多数生物体的必需元素，参与许多生物功能。由于铁是氧化还原活性的过渡金属，已知过量的铁会刺激活性氧（ROS）的形成并加剧细胞毒性。铁缺乏症是世界上最常见的营养缺乏症（约占人口的30%），比铁过载更常见。然而，铁缺乏对ROS诱导的细胞毒性和维持细胞内氧化还原稳态的影响还没有完全了解。本研究报告的影响，铁缺乏对细胞毒性诱导的几种活性氧发生器的评价。与过氧化氢和erastin相反，2，3-二甲氧基-1，4-萘醌（DMNQ）（一种诱导细胞内超氧阴离子形成的氧化还原循环剂）的细胞毒性因缺铁而加剧。细胞色素b5还原酶被鉴定为负责铁耗竭条件下DMNQ的氧化还原循环的候选酶。此外，DMNQ诱导的细胞内ROS积累和NADH/NAD+比值的降低被铁缺乏增强。这些负面变化被发现通过在最初表现出非常低的NQO 1表达的肾脏来源的细胞中过表达NAD（P）H：醌氧化还原酶1（NQO 1）来改善。这些结果表明，NQO 1在铁耗尽条件下对氧化还原循环醌介导的细胞毒性起保护作用。这是因为NQO 1通过醌的双电子还原产生毒性较小的氢醌。本文报道的集体研究结果表明，不仅铁超载，铁缺乏也会加剧ROS介导的细胞毒性。
Iron, an essential element for most of living organisms, participates in many biological functions. Since iron is redox-active transition metal, it is known that excessive levels stimulate the formation of reactive oxygen species (ROS) and exacerbate cytotoxicity. An iron deficiency is the most common nutritional deficiency disorder in the world (about 30% of the population) and is more common than cases of iron overload. However, the effects of iron deficiency on ROS-induced cytotoxicity and the maintenance of intracellular redox homeostasis are not fully understood. The present study reports on an evaluation of the effects of iron deficiency on cytotoxicity induced by several ROS generators. In contrast to hydrogen peroxide and erastin, the cytotoxicity of 2,3-dimethoxy-1,4-naphthoquinone (DMNQ), a redox cycling agent that induces intracellular superoxide anion formation, was exacerbated by iron deficiency. Cytochrome b5reductase was identified as a candidate enzyme responsible for the redox cycling of DMNQ under conditions of iron depletion. Moreover, the DMNQ-induced intracellular accumulation of ROS and a decrease in NADH/NAD+ratios were enhanced by an iron deficiency. These negative changes were found to be ameliorated by overexpressing NAD(P)H:quinone oxidoreductase 1 (NQO1) in kidney-derived cells that originally showed a very low expression of NQO1. These results indicate that NQO1 plays a protective role against redox cycling quinone-mediated cytotoxicity under iron-depleted conditions. This is because NQO1 generates less-toxic hydroquinones via the two-electron reduction of quinones. The collective findings reported herein demonstrate that not only an iron overload but also an iron deficiency exacerbates ROS-mediated cytotoxicity.
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影响因子：
5.6
作者：
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通讯作者：
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DOI：
10.3390/molecules190914902
发表时间：
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影响因子：
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DOI：
--
发表时间：
2011
期刊：
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影响因子：
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