Evidence map›Paper›PMID 39252618›Full record

ArticleCNS & neurological disorders drug targets2025

Nadolol Attenuates Brain Cell Ferroptosis in Ischemic Stroke Rats by Targeting the HOIL-1/IRP2 Pathway.

Xiao-Yan Yang, Wen-Jun Zhu, Di-Chen, Dan Peng, Jun Peng, Zhi-Jun Zhou, Xiu-Ju Luo

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Article in CNS & neurological disorders drug targets, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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2citing papers in PubMed
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2 citing papers in PubMed.

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5 · Who and what money

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7 authors.

Xiao-Yan YangDepartment of Laboratory Medicine, The Third Xiangya Hospital of Central South University, Changsha 410013, China.
Wen-Jun ZhuDepartment of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, China.
Di-ChenDepartment of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, China.
Dan PengDepartment of Laboratory Medicine, The Third Xiangya Hospital of Central South University, Changsha 410013, China.
Jun PengDepartment of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, China.
Zhi-Jun ZhouDepartment Laboratory Animals, Central South University, Changsha 410013, China.
Xiu-Ju LuoDepartment of Laboratory Medicine, The Third Xiangya Hospital of Central South University, Changsha 410013, China.ORCID 0000-0002-4605-0148

Funding

Changsha Municipal Natural Science Foundation, China kq 2014145National Natural Science Foundation of China 82073849, 82173815, 81872873Natural Science Foundation of Hunan Province, China 2021JJ30032
6 · The paper itself

Abstract

introductionHeme-oxidized iron regulatory protein 2 (IRP2) ubiquitin ligase-1 (HOIL-1) is believed to contribute to the ubiquitination of IRP2, which facilitates the transcription of transferrin receptor 1 (TfR1) while preventing the transcription of ferroportin-1 (FPN-1). Bioinformatics analysis predicts that nadolol (a β-blocker) interacts with the HOIL-1.

methodThe present study is intended to explore whether nadolol suppresses ferroptosis in the brains of rats suffering from ischemic stroke via targeting the HOIL-1/IRP2 pathway. A rat model of ischemic stroke was established by blocking the middle cerebral artery for 2 h plus 24 h reperfusion, and nadolol (2.5 or 5 mg/kg) was given at 1h after reperfusion. HT22 cells were subjected to 12 h of hypoxia, followed by 24 h of reoxygenation for simulating ischemic stroke, and nadolol (0.1 or 0.25 μM) was administered to the culture medium before reoxygenation.

resultsThe stroke rats showed evident brain injury (increases in neurological deficit score and infarct volume) and ferroptosis, along with up-regulation of IRP2 and TfR1 while downregulation of HOIL-1 and FPN-1; these phenomena were reversed in the presence of nadolol. In the cultured HT22 cells, hypoxia/reoxygenation-induced LDH release, ferroptosis, and changes in the levels of relevant proteins (IRP2, TfR1, HOIL-1, and FPN-1) were also reversed by nadolol.

conclusionIn terms of these findings, it is concluded that nadolol can protect the ischemic rats' brains against ferroptosis by targeting the HOIL-1/IRP2 pathway, thereby preventing intracellular iron overload. Thus, nadolol may be a novel indication for treating patients with ischemic stroke.

Indexed as

BrainFerroptosisIron Regulatory Protein 2Ischemic StrokeUbiquitin-Protein LigasesAnimalsBrain IschemiaDisease Models, AnimalMaleRatsRats, Sprague-DawleySignal TransductionIron Regulatory Protein 2Ubiquitin-Protein LigasesferroptosisHOIL-1hypoxia/reoxygenation.IRP2Ischemic strokeNadolol

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.