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首页> 外文期刊>RSC Advances >Extracellular electron transfer mediated by a cytocompatible redox polymer to study the crosstalk among the mammalian circadian clock, cellular metabolism, and cellular redox state
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Extracellular electron transfer mediated by a cytocompatible redox polymer to study the crosstalk among the mammalian circadian clock, cellular metabolism, and cellular redox state

机译：由细胞偶联氧化还原聚合物介导的细胞外电子转移，以研究哺乳动物昼夜昼夜时钟，细胞代谢和细胞氧化还原状态的串扰

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摘要

The circadian clock is an endogenous biological timekeeping system that controls various physiological and cellular processes with a 24 h rhythm. The crosstalk among the circadian clock, cellular metabolism, and cellular redox state has attracted much attention. To elucidate this crosstalk, chemical compounds have been used to perturb cellular metabolism and the redox state. However, an electron mediator that facilitates extracellular electron transfer (EET) has not been used to study the mammalian circadian clock due to potential cytotoxic effects of the mediator. Here, we report evidence that a cytocompatible redox polymer pMFc (2-methacryloyloxyethyl phosphorylcholine-co-vinyl ferrocene) can be used as the mediator to study the mammalian circadian clock. EET mediated by oxidized pMFc (ox-pMFc) extracted intracellular electrons from human U2OS cells, resulting in a longer circadian period. Analyses of the metabolome and intracellular redox species imply that ox-pMFc receives an electron from glutathione, thereby inducing pentose phosphate pathway activation. These results suggest novel crosstalk among the circadian clock, metabolism, and redox state. We anticipate that EET mediated by a redox cytocompatible polymer will provide new insights into the mammalian circadian clock system, which may lead to the development of new treatments for circadian clock disorders.
机译：昼夜节点是内源性生物计时系统，可控制24小时节奏的各种生理和细胞过程。昼夜钟表中的串扰，细胞新陈代谢和细胞氧化还原状态引起了很多关注。为了阐明这种串扰，化合物已经用于扰动细胞代谢和氧化还原状态。然而，促进细胞外电子转移（EET）的电子介体尚未被用于研究哺乳动物昼夜速度，因为介质的潜在细胞毒性作用。在这里，我们报告了一种细胞偶联氧化还原聚合物PMFc（2-甲基丙烯酰氧基乙基磷胆碱 - 共乙烯基二茂铁）可以用作研究哺乳动物昼夜钟的介体。由氧化PMFC（OX-PMFC）介导的EET从人U2OS细胞中提取细胞内电子，导致昼夜节约期更长。代谢物和细胞内氧化还原物质的分析意味着OX-PMFC从谷胱甘肽接收电子，从而诱导戊糖磷酸途径活化。这些结果表明了昼夜节奏，新陈代谢和氧化还原状态的新型串扰。我们预计氧化还原细胞势不可化性聚合物介导的EET将为哺乳动物昼夜昼夜钟表系统提供新的见解，这可能导致昼夜节奏疾病的新治疗方法。

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  • 来源
    《RSC Advances》 |2020年第3期|共10页
  • 作者

    Ishikawa Masahito; Kawai Kazuki; Kaneko Masahiro; Tanaka Kenya; Nakanishi Shuji; Hori Katsutoshi;

  • 作者单位

    Nagoya Univ Grad Sch Engn Dept Biomol Engn Chikusa Ku Furo Cho Nagoya Aichi 4648603 Japan;

    Nagoya Univ Grad Sch Engn Dept Biomol Engn Chikusa Ku Furo Cho Nagoya Aichi 4648603 Japan;

    Univ Tokyo Sch Engn Dept Mat Engn Bunkyo Ku 7-3-1 Hongo Tokyo 1138656 Japan;

    Osaka Univ Grad Sch Engn Sci 1-3 Machikaneyama Toyonaka Osaka 5608531 Japan;

    Osaka Univ Grad Sch Engn Sci 1-3 Machikaneyama Toyonaka Osaka 5608531 Japan;

    Nagoya Univ Grad Sch Engn Dept Biomol Engn Chikusa Ku Furo Cho Nagoya Aichi 4648603 Japan;

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