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FoxO1 Controls Redox Regulation and Cellular Physiology of BV-2 Microglial Cells

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Abstract

Microglia are brain-resident macrophage-like cells that play critical roles in diverse pathophysiological conditions, including development, neurogenesis, tissue damage, and pathogenic infection. Identifying molecular switches that govern the fate and function of microglia would be valuable for maintaining brain homeostasis. Forkhead box protein O1 (FoxO1) is the first identified gene in the FoxO family and serves as a potent transcriptional regulator that participates in development, apoptosis, metabolism, and stress response. It has been recently reported that FoxO1 expression is downregulated in human microglia with age, but the role of FoxO1 has not been characterized so far. In the present study, we investigated the molecular function of FoxO1 in microglia by utilizing BV-2 cells. By generating FoxO1-deficient BV-2 microglia through Crispr/Cas9 system, we analyzed the influence of FoxO1 on redox status, metabolism, and polarization of microglia. Our data clearly showed that FoxO1 deficiency suppressed oxidative stress and cell death. In addition, FoxO1 level could modulate metabolic status and polarizing potential of BV-2 microglia. FoxO1 might be a critical element for the regulation of microglial cell physiology and the maintenance of the brain homeostasis.

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Availability of Data and Materials

The data used to support the findings of the study is included in the article, and the data are available from the corresponding author upon request.

Abbreviations

OCR:

Oxygen consumption rate

Veh:

Vehicle

LPS:

Lipopolysaccharide

IFN‐γ:

Interferon gamma

TNF‐α:

Tumor necrosis factor alpha

IL‐1β:

Interleukin 1 beta

SOD:

Superoxide dismutase

ROS:

Reactive oxygen species

TGF‐β:

Transforming growth factor beta

iNOS:

Inducible nitric oxide synthase

xCT:

Cystine/glutamate antiporter

CNS:

Central nervous system

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Funding

This research was supported by Kyungpook National University Research Fund, 2021.

Author information

Authors and Affiliations

  1. Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu, 41940, Republic of Korea

    Chaeeun Seong & Hyeon Ji Kim

  2. Department of Oral Medicine, School of Dentistry, Kyungpook National University, Daegu, 41940, Republic of Korea

    Jin-Seok Byun

  3. Division of Infectious Disease, Department of Internal Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, 41940, Republic of Korea

    Yoonjung Kim

  4. Department of Pharmacology, School of Dentistry, Brain Science and Engineering Institute, Kyungpook National University, Daegu, 41940, Republic of Korea

    Do-Yeon Kim

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  1. Chaeeun Seong
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Contributions

All authors contributed to the study conception and design. Material preparation was performed by Chaeeun Seong, Jin-Seok Byun, Yoonjung Kim, and Do-Yeon Kim. Data collection and analysis were performed by Chaeeun Seong, Hyeon Ji Kim, and Do-Yeon Kim. The first draft of the manuscript was written by Chaeeun Seong and Do-Yeon Kim, and all authors commented on previous versions of the manuscript. Manuscript revision was performed by Chaeeun Seong, Jin-Seok Byun, Yoonjung Kim, and Do-Yeon Kim. All authors read and approved the final manuscript.

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Correspondence to Jin-Seok Byun, Yoonjung Kim or Do-Yeon Kim.

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Seong, C., Kim, H.J., Byun, JS. et al. FoxO1 Controls Redox Regulation and Cellular Physiology of BV-2 Microglial Cells. Inflammation 46, 752–762 (2023). https://doi.org/10.1007/s10753-022-01771-5

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  • DOI: https://doi.org/10.1007/s10753-022-01771-5

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