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Dexmedetomidine enables copper homeostasis in cerebral ischemia/reperfusion via ferredoxin 1

Excessive oxygen free radicals and toxic substances are generated in cerebral ischemia-reperfusion (I/R) process. Dexmedetomidine (DEX), a common anesthetic and sedative drug, can considerably boost glutathione (GSH), which has anti-copper influx effects. Focusing on cuproptosis, the mechanism of DE...

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Autores principales: Guo, Qingduo, Ma, Meina, Yu, Hong, Han, Yuepeng, Zhang, Dong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10173798/
https://www.ncbi.nlm.nih.gov/pubmed/37162502
http://dx.doi.org/10.1080/07853890.2023.2209735
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author Guo, Qingduo
Ma, Meina
Yu, Hong
Han, Yuepeng
Zhang, Dong
author_facet Guo, Qingduo
Ma, Meina
Yu, Hong
Han, Yuepeng
Zhang, Dong
author_sort Guo, Qingduo
collection PubMed
description Excessive oxygen free radicals and toxic substances are generated in cerebral ischemia-reperfusion (I/R) process. Dexmedetomidine (DEX), a common anesthetic and sedative drug, can considerably boost glutathione (GSH), which has anti-copper influx effects. Focusing on cuproptosis, the mechanism of DEX in the I/R was revealed. Using the I/R rat model, the effects of DEX and the copper chelator D-penicillamine on cerebral infarct volume, copper levels, mitochondrial respiration and membrane potential, GSH content, and enrichment of cuproptosis functional proteins were examined. The involvement of ferredoxin 1 (FDX1) in the DEX regulatory pathway was verified by overexpressing FDX1 in vitro. DEX could significantly reduce cerebral infarction in rats, reduce copper levels, maintain mitochondrial functions, increase GSH, and reduce the content of key proteins related to cuproptosis. These aspects were replicated in vitro KEY MESSAGES: Dexmedetomidine reduces cerebral infarction in the I/R rat models. Dexmedetomidine reduces cuproptosis in the I/R rat models. FDX1, an upstream of protein fatty acylation, mediates regulation of Dexmedetomidine.
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spelling pubmed-101737982023-05-12 Dexmedetomidine enables copper homeostasis in cerebral ischemia/reperfusion via ferredoxin 1 Guo, Qingduo Ma, Meina Yu, Hong Han, Yuepeng Zhang, Dong Ann Med Toxicology Excessive oxygen free radicals and toxic substances are generated in cerebral ischemia-reperfusion (I/R) process. Dexmedetomidine (DEX), a common anesthetic and sedative drug, can considerably boost glutathione (GSH), which has anti-copper influx effects. Focusing on cuproptosis, the mechanism of DEX in the I/R was revealed. Using the I/R rat model, the effects of DEX and the copper chelator D-penicillamine on cerebral infarct volume, copper levels, mitochondrial respiration and membrane potential, GSH content, and enrichment of cuproptosis functional proteins were examined. The involvement of ferredoxin 1 (FDX1) in the DEX regulatory pathway was verified by overexpressing FDX1 in vitro. DEX could significantly reduce cerebral infarction in rats, reduce copper levels, maintain mitochondrial functions, increase GSH, and reduce the content of key proteins related to cuproptosis. These aspects were replicated in vitro KEY MESSAGES: Dexmedetomidine reduces cerebral infarction in the I/R rat models. Dexmedetomidine reduces cuproptosis in the I/R rat models. FDX1, an upstream of protein fatty acylation, mediates regulation of Dexmedetomidine. Taylor & Francis 2023-05-10 /pmc/articles/PMC10173798/ /pubmed/37162502 http://dx.doi.org/10.1080/07853890.2023.2209735 Text en © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.
spellingShingle Toxicology
Guo, Qingduo
Ma, Meina
Yu, Hong
Han, Yuepeng
Zhang, Dong
Dexmedetomidine enables copper homeostasis in cerebral ischemia/reperfusion via ferredoxin 1
title Dexmedetomidine enables copper homeostasis in cerebral ischemia/reperfusion via ferredoxin 1
title_full Dexmedetomidine enables copper homeostasis in cerebral ischemia/reperfusion via ferredoxin 1
title_fullStr Dexmedetomidine enables copper homeostasis in cerebral ischemia/reperfusion via ferredoxin 1
title_full_unstemmed Dexmedetomidine enables copper homeostasis in cerebral ischemia/reperfusion via ferredoxin 1
title_short Dexmedetomidine enables copper homeostasis in cerebral ischemia/reperfusion via ferredoxin 1
title_sort dexmedetomidine enables copper homeostasis in cerebral ischemia/reperfusion via ferredoxin 1
topic Toxicology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10173798/
https://www.ncbi.nlm.nih.gov/pubmed/37162502
http://dx.doi.org/10.1080/07853890.2023.2209735
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