Volume 22 Issue 5
May  2024
Turn off MathJax
Article Contents
Article Navigation >  Chinese Journal of General Practice  > 2024  >  22(5): 850-854
CAI Ke, WANG Qinpeng, WEI Yangyang, LI Tingting, WANG Guojuan, LIANG Cheng. Research progress on mitochondrial pyroptosis mechanism in ischemic stroke[J]. Chinese Journal of General Practice, 2024, 22(5): 850-854. doi: 10.16766/j.cnki.issn.1674-4152.003518
Citation: CAI Ke, WANG Qinpeng, WEI Yangyang, LI Tingting, WANG Guojuan, LIANG Cheng. Research progress on mitochondrial pyroptosis mechanism in ischemic stroke[J]. Chinese Journal of General Practice, 2024, 22(5): 850-854. doi: 10.16766/j.cnki.issn.1674-4152.003518
shu

Research progress on mitochondrial pyroptosis mechanism in ischemic stroke

doi: 10.16766/j.cnki.issn.1674-4152.003518

  • Department of Neurology ICU, Lanzhou University Second Hospital, Lanzhou, Gansu 730030, China

Funds:

 21JR11RA129

  • Received Date: 2024-01-25
    Available Online: 2024-07-20
    Abstract
  • As the most common cerebrovascular disease, ischemic stroke has the characteristics of high incidence, high mortality, high disability rate, and high recurrence rate, which brings a heavy burden to patients, families, and society. The main purpose of its treatment is to timely open blood vessels to restore perfusion, rescue ischemic penumbra, and improve neurological function. Research on the pathophysiological mechanism and treatment of ischemic stroke has always been a hot spot. A large number of studies have shown that neuroinflammation is an important mechanism of ischemic stroke. As an inflammatory cell death mode, pyroptosis is closely related to a variety of diseases and injury mechanisms, including the occurrence and development of ischemic stroke. There are a variety of key proteins in the process of pyroptosis, such as inflammasome, caspase-1, and Gasdermin D (GSDMD). GSDMD, as the executive protein of pyroptosis, can punch holes in the cell membrane, causing inflammatory factors such as IL-1β and IL-18 to be released into the extracellular space to produce an inflammatory response. Recent studies have found that GSDMD can not only punch holes in the cell membrane but also destroy the mitochondrial membrane by punching holes, leading to impaired mitochondrial function and release of mitochondrial content. The mitochondrial membrane damage occurs before the cell membrane damage, which not only expands the pyroptosis process but also induces cell death through other pathways. Therefore, inhibiting the perforating function of GSDMD and improving the mitochondrial function of ischemic cells through mitochondrial transplantation can effectively inhibit the inflammatory response and improve the function of the ischemic penumbra, thus playing a neuroprotective role. In this review, we briefly introduce the process of pyroptosis and the mechanism of GSDMD drilling in the process of pyroptosis, focusing on the process of mitochondrial pyroptosis and its related research progress in ischemic stroke, and looking for new ideas for the treatment of ischemic stroke.

     

    • FullText(HTML)
  • loading
    • References(45)
  • [1]
    张然, 田浩林, 王丽婷, 等. 静脉溶栓及血管内治疗急性脑梗死的国内研究进展[J]. 中华全科医学, 2020, 18(11): 1916-1920. doi: 10.16766/j.cnki.issn.1674-4152.001653

    ZHANG R, TIAN H L, WANG L T, et al. Domestic research progress of intravenous thrombolysis and endovascular treatment of acute cerebral infarction[J]. Chinese Journal of General Practice, 2020, 18(11): 1916-1920. doi: 10.16766/j.cnki.issn.1674-4152.001653
    [2]
    MIAO R, JIANG C, CHANG W Y, et al. Gasdermin D permeabilization of mitochondrial inner and outer membranes accelerates and enhances pyroptosis[J]. Immunity, 2023, 56(11): 2523-2541. doi: 10.1016/j.immuni.2023.10.004
    [3]
    RAO Z, ZHU Y, YANG P, et al. Pyroptosis in inflammatory diseases and cancer[J]. Theranostics, 2022, 12(9): 4310-4329. doi: 10.7150/thno.71086
    [4]
    ZHENG D, LIWINSKI T, ELINAV E. Inflammasome activation and regulation: toward a better understanding of complex mechanisms[J]. Cell Discov, 2020, 6: 36.
    [5]
    LIAQAT A, ASAD M, SHOUKAT F, et al. A spotlight on the underlying activation mechanisms of the NLRP3 inflammasome and its role in atherosclerosis: a review[J]. Inflammation, 2020, 43(6): 2011-2020. doi: 10.1007/s10753-020-01290-1
    [6]
    SWANSON K V, DENG M, TING J P. The NLRP3 inflammasome: molecular activation and regulation to therapeutics[J]. Nat Rev Immunol, 2019, 19(8): 477-489. doi: 10.1038/s41577-019-0165-0
    [7]
    QIAN Z, ZHAO Y, WAN C, et al. Pyroptosis in the initiation and progression of atherosclerosis[J]. Front Pharmacol, 2021, 12: 652963. DOI: 10.3389/FPHAR.2021.652963.
    [8]
    梅旦, 张玲玲, 魏伟. 细胞焦亡机制及与疾病的关系[J]. 生理科学进展, 2020, 51(2): 151-156. doi: 10.3969/j.issn.0559-7765.2020.02.018

    MEI D, ZHANG L L, WEI W. Mechanism of pyroptosis and its relationship with diseases[J]. Progress in Physiological Sciences, 2020, 51(2): 151-156. doi: 10.3969/j.issn.0559-7765.2020.02.018
    [9]
    HU L, SHAO C Z, PAN L Y, et al. Lack of STAT6 enhances murine acute lung injury through NLRP3/ p38 MAPK signaling pathway in macrophages[J]. BMC Immunology, 2022, 23(1): 25. doi: 10.1186/s12865-022-00500-9
    [10]
    KAYAGAKI N, LEE B L, STOWE I B, et al. IRF2 transcriptionally induces GSDMD expression for pyroptosis[J]. Sci Signal, 2019, 12(582): eaax4917. DOI: 10.1126/scisignal.aax4917.
    [11]
    NIU X F, YAO Q, LI W F, et al. Harmine mitigates LPS-induced acute kidney injury through inhibition of the TLR4-NF-κB/NLRP3 inflammasome signalling pathway in mice[J]. Eur J Pharmacol, 2019, 849: 160-169. doi: 10.1016/j.ejphar.2019.01.062
    [12]
    XIA S, ZHANG Z, MAGUPALLI V G, et al. Gasdermin D pore structure reveals preferential release of mature interleukin-1[J]. Nature, 2021, 593(7860): 607-611. doi: 10.1038/s41586-021-03478-3
    [13]
    LIU X, XIA S, ZHANG Z, et al. Channelling inflammation: gasdermins in physiology and disease[J]. Nat Rev Drug Discov, 2021, 20(5): 384-405. doi: 10.1038/s41573-021-00154-z
    [14]
    李陈广, 麦凤怡, 梁靖蓉, 等. Gasdermin D蛋白的研究进展[J]. 中国药理学通报, 2023, 39(5): 817-822. doi: 10.12360/CPB202202015

    LI C G, MAI F Y, LIANG J R. Research progress of Gasdermin D protein[J]. Chinese Pharmacological Bulletin, 2023, 39(5): 817-822. doi: 10.12360/CPB202202015
    [15]
    RIGOTTO G, BASSO E. Mitochondrial dysfunctions: a thread sewing together Alzheimer ' s disease, diabetes, and obesity[J]. Oxid Med Cell Longev, 2019, 2019: 7210892. DOI: 10.1155/2019/7210892.
    [16]
    MOHD S, STAYTON A S, KEHKASHAN P, et al. Intranasal delivery of mitochondria attenuates brain injury by AMPK and SIRT1/ PGC-1α pathways in a murine model of photothrombotic stroke[J]. Mol Neurobiol, 2023. DOI: 10.1007/s12035-023-03739-4.
    [17]
    GONZALEZ-FRANQUESA A, STOCKS B, CHUBANAVA S, et al. Mass-spectrometry-based proteomics reveals mitochondrial supercomplexome plasticity[J]. Cell Rep, 2021, 35(8): 109180. DOI: 10.1016/j.celrep.2021.109180.
    [18]
    GRVNEWALD A, KUMAR K R, SUE C M. New insights into the complex role of mitochondria in Parkinson ' s disease[J]. Prog Neurobiol, 2019, 177: 73-93. doi: 10.1016/j.pneurobio.2018.09.003
    [19]
    MARCUS L, STEFANIE S, PEER K, et al. Ischemia time impacts on respiratory chain functions and Ca2+-handling of cardiac subsarcolemmal mitochondria subjected to ischemia reperfusion injury[J]. J Cardiothorac Surg, 2019, 14(1): 92. doi: 10.1186/s13019-019-0911-1
    [20]
    张伟平, 屈洪党, 许力. 丁苯酞注射液对脑梗死患者血清细胞凋亡因子水平的影响[J]. 中华全科医学, 2019, 17(7): 1087-1089, 1190. doi: 10.16766/j.cnki.issn.1674-4152.000869

    ZHANG W P, QU H D, XU L. Effect of butylphthalide injection on serum levels of apoptotic factors in patients with cerebral infarction[J]. Chinese Journal of General Practice, 2019, 17(7): 1087-1089, 1190. doi: 10.16766/j.cnki.issn.1674-4152.000869
    [21]
    DE VASCONCELOS N M, VAN OPDENBOSCH N, VAN GORP H, et al. Single-cell analysis of pyroptosis dynamics reveals conserved GSDMD-mediated subcellular events that precede plasma membrane rupture[J]. Cell Death Differ, 2019, 26(1): 146-161. doi: 10.1038/s41418-018-0106-7
    [22]
    ROGERS C, ERKES D A, NARDONE A, et al. Gasdermin pores permeabilize mitochondria to augment caspase-3 activation during apoptosis and inflammasome activation[J]. Nat Commun, 2019, 10(1): 1689. DOI: 10.1038/s41467-019-09397-2.
    [23]
    HUANG L S, HONG Z, WU W, et al. mtDNA activates cGAS signaling and suppresses the YAP-Mediated endothelial cell proliferation program to promote inflammatory injury[J]. Immunity, 2020, 52(3): 475-486. doi: 10.1016/j.immuni.2020.02.002
    [24]
    DE TORRE-MINGUELA C, GOMEZ A I, COUILLIN I, et al. Gasdermins mediate cellular release of mitochondrial DNA during pyroptosis and apoptosis[J]. FASEB J, 2021, 35(8): e21757. DOI: 10.1096/fj.202100085R.
    [25]
    DE VASCONCELOS N M, LAMKANFI M. Recent insights on inflammasomes, gasdermin pores, and pyroptosis[J]. Cold Spring Harb Perspect Biol, 2020, 12(5): a036392. DOI: 10.1101/cshperspect.a036392.
    [26]
    CHU C T, JI J, DAGDA R K, et al. Cardiolipin externalization to the outer mitochondrial membrane acts as an elimination signal for mitophagy in neuronal cells[J]. Nat Cell Biol, 2013, 15(10): 1197-1205. doi: 10.1038/ncb2837
    [27]
    PIZZUTO M, PELEGRIN P. Cardiolipin in immune signaling and cell death[J]. Trends Cell Biol, 2020, 30(11): 892-903. doi: 10.1016/j.tcb.2020.09.004
    [28]
    MAMUN A A, WU Y Q, NASRIN F, et al. Role of pyroptosis in diabetes and its therapeutic implications[J]. J Inflamm Res, 2021, 14: 2187-2206. doi: 10.2147/JIR.S291453
    [29]
    JAYARAJ L R, AZIMULLAH S, BEIRAM R, et al. Neuroinflammation: friend and foe for ischemic stroke[J]. J Neuroinflammation, 2019, 16(1): 1-24. doi: 10.1186/s12974-018-1391-2
    [30]
    LYKKE K L, BENTE F, HJELM B C. Post-stroke inflammation-target or tool for therapy?[J]. Acta Neuropatho, 2019, 137 (5): 693-714. doi: 10.1007/s00401-018-1930-z
    [31]
    MALHOTRA K, LIEBESKIND D S. Collaterals in ischemic stroke[J]. Brain Hemorrhages, 2020, 1: 6-12. doi: 10.1016/j.hest.2019.12.003
    [32]
    ANAMARIA J, AUREL S. Neuroinflammation in cerebral ischemia and Ischemia/Reperfusion injuries: from pathophysiology to therapeutic strategies[J]. Int J Mol Sci, 2021, 23(1): 14. DOI: 10.3390/ijms23010014.
    [33]
    WANG L Y, XIONG X X, ZHANG L Y, et al. Neurovascular Unit: a critical role in ischemic stroke[J]. CNS Neurosci Ther, 2021, 27(1): 7-16. doi: 10.1111/cns.13561
    [34]
    KARTIK P, RUKMANI P, CHANDAN C, et al. Role of NLRP3 inflammasome in stroke pathobiology: current therapeutic avenues and future perspective[J]. ACS Chem Neurosci, 2023, 15(1): 31-55.
    [35]
    FIACHRA H, LIRAZ G S, NATALIA C K, et al. Succination inactivates gasdermin D and blocks pyroptosis[J]. Science (New York, N.Y. ), 2020, 369(6511): 1633-1637. doi: 10.1126/science.abb9818
    [36]
    HU J, LIU X, ZHAO J X, et al. Identification of pyroptosis inhibitors that target a reactive cysteine in Gasdermin D[J]. Cancer Immunol Res, 2019, 7(2): A132. DOI: 10.1158/2326-6074.CRICIMTEATIAACR18-A132.
    [37]
    HAN B J, XU J J, SHI X W, et al. DL-3-n-Butylphthalide attenuates myocardial hypertrophy by targeting Gasdermin D and inhibiting Gasdermin D mediated inflammation[J]. Front Pharmacol, 2021, 12: 688140. DOI: 10.3389/fphar.2021.688140.
    [38]
    HAN C Y, HU Q H, YU A Q, et al. Mafenide derivatives inhibit neuroinflammation in Alzheimer ' s disease by regulating pyroptosis[J]. J Cell Mol Med, 2021, 25(22): 10534-10542. doi: 10.1111/jcmm.16984
    [39]
    WANG Q Y, ZHENG J S, HU Q Y, et al. Magnesium protects against sepsis by blocking gasdermin D N-terminal-induced pyroptosis[J]. Cell Death Differ, 2020, 27(2): 466-481. doi: 10.1038/s41418-019-0366-x
    [40]
    罗兰, 张凤秋. 细胞间线粒体转移的作用及机制研究进展[J]. 口腔生物医学, 2023, 14(3): 202-205. doi: 10.3969/j.issn.1674-8603.2023.03.012

    LUO L, ZHANG Q F. Research progress on the role and mechanism of mitochondrial transfer between cells[J]. Oral Biomedicine, 2023, 14(3): 202-205. doi: 10.3969/j.issn.1674-8603.2023.03.012
    [41]
    DOULAMIS I P, GUARIENTO A, DUIGNAN T, et al. Mitochondrial transplantation for myocardial protection in diabetic hearts[J]. Eur J Cardiothorac Surg, 2020, 57(5): 836-845. doi: 10.1093/ejcts/ezz326
    [42]
    NAKAMURA Y, PARK J H, HAYAKAWA K. Therapeutic use of extracellular mitochondria in CNS injury and disease[J]. Exp Neurol, 2020, 324: 113114. DOI: 10.1016/j.expneurol.2019.113114.
    [43]
    SUN L, ZHAO Z Y, GUO J, et al. Mitochondrial transplantation confers protection against the effects of ischemic stroke by repressing microglial pyroptosis and promoting neurogenesis[J]. Neural Regen Res, 2024, 19(6): 1325-1335. doi: 10.4103/1673-5374.385313
    [44]
    ZHANG Z, MA Z, YAN C, et al. Muscle-derived autologous mitochondrial transplantation: a novel strategy for treating cerebral ischemic injury[J]. Behav Brain Res, 2019, 356: 322-331. doi: 10.1016/j.bbr.2018.09.005
    [45]
    ALI POUR P, KENNEY M C, KHERADVAR A. Bioenergetics consequences of mitochondrial transplantation in cardiomyocytes[J]. J Am Heart Assoc, 2020, 9 (7): e014501. DOI: 10.1161/JAHA.119.014501.
    • Relative Articles
    • Supplements(0)
    • Cited By
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索
    Get Citation
    PDF
    XML

    Article Metrics

    Article views (34) PDF downloads(2) Cited by()
    Proportional views
    Related

    Address：No. 287, Changhuai Road, Bengbu, Anhui Province, 233004, P.R.ChinaphoneNo：0552-3066635； 0552-3051890Email：zhqkyx@163.com

    Copyright © Chinese Journal of General Practice皖ICP备2020018345号-2

    Supported by: Beijing Renhe Information Technology Co., Ltd.    

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return