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Carbon Monoxide Protects Neural Stem Cells Against Iron Overload by Modulating the Crosstalk Between Nrf2 and NF-κB Signaling

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Abstract

Although accumulating evidences have demonstrated pro-survival effects of CO against various insults, the precise mechanism explaining how neural stem cells (NSCs) are protected by CO also remains largely unknown. Here we report CO pro-survival effect on NSCs against iron overload was comparable to that obtained with pharmacological inhibitors of reactive oxygen species (ROS). Its pro-survival effect was accompanied by the inhibition of ROS and subsequent inhibition of NF-κB which is mediated through nuclear factor erythroid 2-related factor 2 (Nrf2), in that activation of Nrf2 by CO inhibited ROS via up-regulation of NQO-1 while down-regulation of Nrf2 reversed the pro-survival effect of CO both in vitro and in vivo. CO-mediated preconditioning results in Nrf2 up-regulation and NF-κB inhibition, suggesting that these two pathways act in an inverse manner to maintain redox homeostasis. Our findings revealed CO preconditioning as a promising treatment strategy to improve efficacy of NSCs transplantation after hemorrhagic stroke.

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All associated data are available on reasonable request.

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Funding

This study was funded by Nanjing Medical University Foundation (Grant No. 2017NJMUD114), Wuxi Municipal Bureau Foundation (Grant No. N20192022) and Top Talent Support Program for young and middle-aged people of Wuxi Health Committee (Grant No. HB2020036).

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Author notes

  1. Xie Zhengxing and Hu Aiying have contributed equally to this article.

Authors and Affiliations

  1. Department of Neurosurgery, The Affiliated Hospital of Jiangsu University, 438, Jiefang Road, Zhenjiang, 212001, Jiangsu Province, China

    Xie Zhengxing & Hu Aiying

  2. Department of Neurosurgery, The Affiliated Wuxi No. 2 People’s Hospital of Nanjing Medical University, 68, Zhongshan Road, Wuxi, 214000, Jiangsu Province, China

    Xie Zhengxing & Miao zengli

  3. Bingtuan Sishi Hospital, 56, Western Xinhua Road, Yining, Xinjiang Province, China

    Zhang Zongqiang

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  1. Xie Zhengxing
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Correspondence to Xie Zhengxing.

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The study was approved by the Ethical committee of The Affiliated Wuxi No. 2 Peoples' Hospital of Nanjing Medical University, Wuxi, China.

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Zhengxing, X., Aiying, H., Zongqiang, Z. et al. Carbon Monoxide Protects Neural Stem Cells Against Iron Overload by Modulating the Crosstalk Between Nrf2 and NF-κB Signaling. Neurochem Res 47, 1383–1394 (2022). https://doi.org/10.1007/s11064-022-03537-9

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  • DOI: https://doi.org/10.1007/s11064-022-03537-9

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