Electroacupuncture inhibits neuronal pyroptosis in ischemic brain injury through modulating SIRT5-mediated NEK7 succinylation

Ischemic stroke is a leading cause of global death. The treatment of this disease can inevitably result in reperfusion, thereby triggering cerebral ischemia-reperfusion injury (IRI) and neuronal pyroptosis. Electroacupuncture derived from traditional acupuncture has been proven to have favorable eff...

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Main Authors: Lili Ma, Meiling Zhang, Ting Chen, Limin Wang, Qilong Deng
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Brain Research Bulletin
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Online Access:http://www.sciencedirect.com/science/article/pii/S0361923024003071
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author Lili Ma
Meiling Zhang
Ting Chen
Limin Wang
Qilong Deng
author_facet Lili Ma
Meiling Zhang
Ting Chen
Limin Wang
Qilong Deng
author_sort Lili Ma
collection DOAJ
description Ischemic stroke is a leading cause of global death. The treatment of this disease can inevitably result in reperfusion, thereby triggering cerebral ischemia-reperfusion injury (IRI) and neuronal pyroptosis. Electroacupuncture derived from traditional acupuncture has been proven to have favorable effects on ameliorating brain IRI and pyroptosis. Hence, the goal of the current research was to elucidate the mechanism governing electroacupuncture in cerebral IRI. We employed middle cerebral artery occlusion (MCAO) model to induce brain IRI. Our results revealed that electroacupuncture attenuated IRI in MCAO mice by minishing brain damage and hindering neuronal pyroptosis. Strikingly, it was discovered that electroacupuncture provoked the decrease of succinylation level and enhanced expression of SIRT5. Then, we demonstrated that knockdown of SIRT5 reversed the role of electroacupuncture in cerebral infarct injury and pyroptosis. In terms of mechanism, SIRT5 impeded the succinylation modification of NEK7 at K81 site to downregulate its expression level. Eventually, overexpression of NEK7 abrogated the impacts of electroacupuncture on MCAO mice. In conclusion, electroacupuncture restrained neuronal pyroptosis after cerebral ischemia via desuccinylating NEK7 in a SIRT5-dependent way.
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institution Kabale University
issn 1873-2747
language English
publishDate 2025-01-01
publisher Elsevier
record_format Article
series Brain Research Bulletin
spelling doaj-art-a6a3ad8680f34b05a59889499ec876352025-01-10T04:37:03ZengElsevierBrain Research Bulletin1873-27472025-01-01220111173Electroacupuncture inhibits neuronal pyroptosis in ischemic brain injury through modulating SIRT5-mediated NEK7 succinylationLili Ma0Meiling Zhang1Ting Chen2Limin Wang3Qilong Deng4Wenzhou Medical University, Chashan University Town, Ouhai District, Wenzhou, Zhejiang 325035, China; Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, No 150, Ximen Street, Linhai, Taizhou, Zhejiang 317000, ChinaTaizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, No 150, Ximen Street, Linhai, Taizhou, Zhejiang 317000, China; Luqiao Hospital, Taizhou Enze Medical Center (Group), No 1, West Xialiqiao Road, Luqiao District, Taizhou, Zhejiang 318050, ChinaTaizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, No 150, Ximen Street, Linhai, Taizhou, Zhejiang 317000, ChinaTaizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, No 150, Ximen Street, Linhai, Taizhou, Zhejiang 317000, China; Luqiao Hospital, Taizhou Enze Medical Center (Group), No 1, West Xialiqiao Road, Luqiao District, Taizhou, Zhejiang 318050, China; Corresponding authors at: Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, No 150, Ximen Street, Linhai, Taizhou, Zhejiang 317000, China.Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, No 150, Ximen Street, Linhai, Taizhou, Zhejiang 317000, China; Luqiao Hospital, Taizhou Enze Medical Center (Group), No 1, West Xialiqiao Road, Luqiao District, Taizhou, Zhejiang 318050, China; Corresponding authors at: Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, No 150, Ximen Street, Linhai, Taizhou, Zhejiang 317000, China.Ischemic stroke is a leading cause of global death. The treatment of this disease can inevitably result in reperfusion, thereby triggering cerebral ischemia-reperfusion injury (IRI) and neuronal pyroptosis. Electroacupuncture derived from traditional acupuncture has been proven to have favorable effects on ameliorating brain IRI and pyroptosis. Hence, the goal of the current research was to elucidate the mechanism governing electroacupuncture in cerebral IRI. We employed middle cerebral artery occlusion (MCAO) model to induce brain IRI. Our results revealed that electroacupuncture attenuated IRI in MCAO mice by minishing brain damage and hindering neuronal pyroptosis. Strikingly, it was discovered that electroacupuncture provoked the decrease of succinylation level and enhanced expression of SIRT5. Then, we demonstrated that knockdown of SIRT5 reversed the role of electroacupuncture in cerebral infarct injury and pyroptosis. In terms of mechanism, SIRT5 impeded the succinylation modification of NEK7 at K81 site to downregulate its expression level. Eventually, overexpression of NEK7 abrogated the impacts of electroacupuncture on MCAO mice. In conclusion, electroacupuncture restrained neuronal pyroptosis after cerebral ischemia via desuccinylating NEK7 in a SIRT5-dependent way.http://www.sciencedirect.com/science/article/pii/S0361923024003071ElectroacupunctureCerebral ischemiaPyroptosisSIRT5/NEK7Succinylation
spellingShingle Lili Ma
Meiling Zhang
Ting Chen
Limin Wang
Qilong Deng
Electroacupuncture inhibits neuronal pyroptosis in ischemic brain injury through modulating SIRT5-mediated NEK7 succinylation
Brain Research Bulletin
Electroacupuncture
Cerebral ischemia
Pyroptosis
SIRT5/NEK7
Succinylation
title Electroacupuncture inhibits neuronal pyroptosis in ischemic brain injury through modulating SIRT5-mediated NEK7 succinylation
title_full Electroacupuncture inhibits neuronal pyroptosis in ischemic brain injury through modulating SIRT5-mediated NEK7 succinylation
title_fullStr Electroacupuncture inhibits neuronal pyroptosis in ischemic brain injury through modulating SIRT5-mediated NEK7 succinylation
title_full_unstemmed Electroacupuncture inhibits neuronal pyroptosis in ischemic brain injury through modulating SIRT5-mediated NEK7 succinylation
title_short Electroacupuncture inhibits neuronal pyroptosis in ischemic brain injury through modulating SIRT5-mediated NEK7 succinylation
title_sort electroacupuncture inhibits neuronal pyroptosis in ischemic brain injury through modulating sirt5 mediated nek7 succinylation
topic Electroacupuncture
Cerebral ischemia
Pyroptosis
SIRT5/NEK7
Succinylation
url http://www.sciencedirect.com/science/article/pii/S0361923024003071
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AT meilingzhang electroacupunctureinhibitsneuronalpyroptosisinischemicbraininjurythroughmodulatingsirt5mediatednek7succinylation
AT tingchen electroacupunctureinhibitsneuronalpyroptosisinischemicbraininjurythroughmodulatingsirt5mediatednek7succinylation
AT liminwang electroacupunctureinhibitsneuronalpyroptosisinischemicbraininjurythroughmodulatingsirt5mediatednek7succinylation
AT qilongdeng electroacupunctureinhibitsneuronalpyroptosisinischemicbraininjurythroughmodulatingsirt5mediatednek7succinylation