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Extracellular Electron Transfer Mediated by a Cytocompatible Redox Polymer Lengthens the Circadian Period of Mammalian Cells

preprint
submitted on 01.10.2019 and posted on 02.10.2019 by Masahito Ishikawa, Kazuki Kawai, Masahiro Kaneko, Kenya Tanaka, Shuji Nakanishi, Katsutoshi Hori
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, extracellular electron transfer (EET) with an electron mediator has not been used to study the mammalian circadian clock due to potential cytotoxic effects of the mediator. Here, we describe the use of EET mediated by pMFc, a cytocompatible redox polymer, on human U2OS cells. EET mediated by oxidized pMFc (ox-pMFc) extracted intracellular electrons, resulting in a longer circadian period. Analyses of the metabolome and intracellular redox species suggest that ox-pMFc receives an electron from glutathione, thereby inducing pentose phosphate pathway activation. We anticipate that redox perturbation via EET will provide new insights into the crosstalk among the circadian clock, metabolism, and redox state, which may lead to the development of new treatments for circadian clock disorders.

History

Email Address of Submitting Author

ishikawa.masahito@chembio.nagoya-u.ac.jp

Institution

Nagoya University

Country

Japan

ORCID For Submitting Author

0000-0001-6390-1031

Declaration of Conflict of Interest

no conflict of interest

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