{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T21:45:55Z","timestamp":1773697555121,"version":"3.50.1"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T00:00:00Z","timestamp":1666656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Neurosci."],"abstract":"<jats:p>Ras-related protein Rab-20 (Rab20) is induced in hypoxia and contributes to hypoxia-induced apoptosis. However, the role and mechanism of Rab20 in cerebral ischemia\/reperfusion (I\/R) injury need to be elucidated. We established a cerebral I\/R injury model in the mice and an oxygen-glucose deprivation\/reoxygenation (OGD\/R) model in HT22 cells to determine the effects of Rab20 in cerebral I\/R injury. Rab20 expression was upregulated in mice after I\/R and in HT22 cells after OGD\/R. Upregulated Rab20 was mainly located in neurons. Rab20 inhibition significantly alleviated brain infarct volume, neurological deficits, and neuronal apoptosis in mice after I\/R. Moreover, Rab20 knockdown significantly ameliorated the OGD\/R-induced inhibition of cell viability and apoptotic cell death in HT22 cells. Rab20 knockdown significantly alleviated OGD\/R-induced mitochondrial fission by repressing mitochondrial dynamin-related protein 1 (Drp-1) recruitment and increasing Drp-1 (Ser637) phosphorylation and ameliorated mitochondrial dysfunction by reducing the mitochondrial reactive oxygen species (ROS) and cellular calcium accumulation and increasing the mitochondrial membrane potential. In addition, Rab20 knockdown significantly alleviated cytochrome c release from the mitochondria into the cytosol in HT22 cells after OGD\/R. Rab20 contributes to cerebral I\/R injury by regulating mitochondria-associated apoptosis pathways. Targeting Rab20 may be an attractive strategy for the treatment of cerebral I\/R injury.<\/jats:p>","DOI":"10.3389\/fnmol.2022.986710","type":"journal-article","created":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T05:35:50Z","timestamp":1666676150000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Ras-related protein Rab-20 inhibition alleviates cerebral ischemia\/reperfusion injury by inhibiting mitochondrial fission and dysfunction"],"prefix":"10.3389","volume":"15","author":[{"given":"Jia","family":"Guo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yujie","family":"Bu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianping","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianxiong","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1083\/jcb.200204081","article-title":"Rab32 is an A-kinase anchoring protein and participates in mitochondrial dynamics.","volume":"158","author":"Alto","year":"2002","journal-title":"J. Cell Biol."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.033860","article-title":"Pramipexole prevents ischemic cell death via mitochondrial pathways in ischemic stroke.","volume":"12","author":"Andrabi","year":"2019","journal-title":"Dis. Model. Mech."},{"key":"B3","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1007\/s00709-019-01439-2","article-title":"Ischemic stroke and mitochondria: Mechanisms and targets.","volume":"257","author":"Andrabi","year":"2020","journal-title":"Protoplasma"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-019-0118-8","article-title":"Ischaemic stroke.","volume":"5","author":"Campbell","year":"2019","journal-title":"Nat. Rev. Dis. Primers"},{"key":"B5","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1016\/j.bbabio.2009.12.017","article-title":"Mitochondrial ion transport pathways: Role in metabolic diseases.","volume":"1797","author":"Cardoso","year":"2010","journal-title":"Biochim. Biophys. Acta Bioenerg."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0116814","article-title":"Role of neuronal NADPH oxidase 1 in the peri-infarct regions after stroke.","volume":"10","author":"Choi","year":"2015","journal-title":"PLoS One"},{"key":"B7","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1016\/j.neuropharm.2008.01.005.Neuropharmacology","article-title":"Mechanisms of Ischemic Brain Damage \u2013 Review Article.","volume":"55","author":"Doyle","year":"2008","journal-title":"Neuropharmacology"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035663","article-title":"Rab20 regulates phagosome maturation in RAW264 macrophages during Fc gamma receptor-mediated phagocytosis.","volume":"7","author":"Egami","year":"2012","journal-title":"PLoS One"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.2307\/j.ctv15vwj9v.23","author":"Farmer","year":"2020","journal-title":"Chapter 15 Black Bride of Christ."},{"key":"B10","doi-asserted-by":"publisher","first-page":"3119","DOI":"10.1523\/JNEUROSCI.1926-19.2020","article-title":"Deletion of a neuronal Drp1 activator protects against cerebral ischemia.","volume":"40","author":"Flippo","year":"2020","journal-title":"J. Neurosci."},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/s11906-020-01120-7","article-title":"Blood Pressure Management in Acute Ischemic Stroke.","volume":"23","author":"G\u0105secki","year":"2021","journal-title":"Curr. Hypertens. Rep."},{"key":"B12","doi-asserted-by":"publisher","first-page":"2800","DOI":"10.2337\/DB16-1488","article-title":"Hypoxia in Combination With Muscle Contraction Improves Insulin Action and Glucose Metabolism in Human Skeletal Muscle via the HIF-1a Pathway.","volume":"66","author":"G\u00f6rgens","year":"2017","journal-title":"Diabetes"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.bbamcr.2010.10.019","article-title":"The GTPase RAB20 is a HIF target with mitochondrial localization mediating apoptosis in hypoxia.","volume":"1813","author":"Hackenbeck","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"B14","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1016\/S0306-4522(01)00125-7","article-title":"Relationship between metabolic dysfunctions, gene responses and delayed cell death after mild focal cerebral ischemia in mice.","volume":"104","author":"Hermann","year":"2001","journal-title":"Neuroscience"},{"key":"B15","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.neuroscience.2019.06.008","article-title":"LRG1 Promotes Apoptosis and Autophagy through the TGF\u03b2-smad1\/5 Signaling Pathway to Exacerbate Ischemia\/Reperfusion Injury.","volume":"413","author":"Jin","year":"2019","journal-title":"Neuroscience"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-015-0264-1","article-title":"MCP-induced protein 1 mediates the minocycline-induced neuroprotection against cerebral ischemia\/reperfusion injury in vitro and in vivo.","volume":"12","author":"Jin","year":"2015","journal-title":"J. Neuroinflammation"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9113710","article-title":"High-glucose-induced rab20 upregulation disrupts gap junction intercellular communication and promotes apoptosis in retinal endothelial and m\u00fcller cells: Implications for diabetic retinopathy.","volume":"9","author":"Kim","year":"2020","journal-title":"J. Clin. Med."},{"key":"B18","doi-asserted-by":"publisher","first-page":"2230","DOI":"10.1074\/jbc.M113.516351","article-title":"A functional interplay between the small GTPase rab11a and mitochondria-shaping proteins regulates mitochondrial positioning and polarization of the actin cytoskeleton downstream of Src family kinases.","volume":"289","author":"Landry","year":"2014","journal-title":"J. Biol. Chem."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.104846","article-title":"Mitophagy inhibitor liensinine suppresses doxorubicin-induced cardiotoxicity through inhibition of Drp1-mediated maladaptive mitochondrial fission.","volume":"157","author":"Liang","year":"2020","journal-title":"Pharmacol. Res."},{"key":"B20","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.neulet.2012.08.039","article-title":"Expression profiling of Rab GTPases reveals the involvement of Rab20 and Rab32 in acute brain inflammation in mice.","volume":"527","author":"Liang","year":"2012","journal-title":"Neurosci. Lett."},{"key":"B21","doi-asserted-by":"publisher","first-page":"4417","DOI":"10.2147\/IJN.S170035","article-title":"Iridium (III) complex-loaded liposomes as a drug delivery system for lung cancer through mitochondrial dysfunction.","volume":"13","author":"Liao","year":"2018","journal-title":"Int. J. Nanomed."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.4172\/2167-0501.1000213.Ischemia-reperfusion","article-title":"Ischemia-reperfusion Injury in the Brain: Mechanisms and Potential Therapeutic Strategies.","volume":"5","author":"Lin","year":"2016","journal-title":"Biochem. Pharmacol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1791","DOI":"10.1161\/01.CIR.0000058460.34453.5A","article-title":"Protein S confers neuronal protection during ischemic\/hypoxic injury in mice.","volume":"107","author":"Liu","year":"2003","journal-title":"Circulation"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02408","article-title":"Pterostilbene attenuates astrocytic inflammation and neuronal oxidative injury after ischemia-reperfusion by inhibiting nf-\u03bab phosphorylation.","volume":"10","author":"Liu","year":"2019","journal-title":"Front. Immunol."},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-01946-7","article-title":"Cottonseed oil alleviates ischemic stroke injury by inhibiting the inflammatory activation of microglia and astrocyte.","volume":"17","author":"Liu","year":"2020","journal-title":"J. Neuroinflammation"},{"key":"B26","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1080\/17425247.2018.1384464.Tissue","article-title":"Tissue plasminogen activator-based nanothrombolysis for ischemic stroke Shan.","volume":"15","author":"Liu","year":"2018","journal-title":"Expert Opin. Drug Deliv."},{"key":"B27","doi-asserted-by":"publisher","first-page":"3437","DOI":"10.1242\/jcs.107.12.3437","article-title":"Cloning and subcellular localization of novel rab proteins reveals polarized and cell type-specific expression.","volume":"107","author":"Lutcke","year":"1994","journal-title":"J. Cell Sci."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1451","DOI":"10.1001\/jama.2015.3058","article-title":"Acute stroke intervention: A systematic review.","volume":"313","author":"Prabhakaran","year":"2015","journal-title":"JAMA"},{"key":"B29","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1038\/nrm2728","article-title":"Rab GTPases as coordinators of vesicle traffic.","volume":"10","author":"Stenmark","year":"2009","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1000","DOI":"10.1111\/jcmm.17189","article-title":"Mitochondrial quality control in stroke: From the mechanisms to therapeutic potentials.","volume":"26","author":"Tian","year":"2022","journal-title":"J. Cell. Mol. Med."},{"key":"B31","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1038\/nature25486.Mitochondria-lysosome","article-title":"Mitochondria-lysosome contacts regulate mitochondrial fission via RAB7 GTP hydrolysis.","volume":"554","author":"Wong","year":"2018","journal-title":"Nature"},{"key":"B32","doi-asserted-by":"publisher","first-page":"2307","DOI":"10.1016\/j.bbadis.2017.06.011","article-title":"Succinate-induced neuronal mitochondrial fission and hexokinase II malfunction in ischemic stroke: Therapeutical effects of kaempferol.","volume":"1863","author":"Wu","year":"2017","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"B33","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.redox.2018.03.002","article-title":"Diverse roles of mitochondria in ischemic stroke.","volume":"16","author":"Yang","year":"2018","journal-title":"Redox Biol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1687","DOI":"10.7150\/ijms.53603","article-title":"Qingda granule exerts neuroprotective effects against ischemia\/reperfusion-induced cerebral injury via lncRNA GAS5\/miR-137 signaling pathway.","volume":"18","author":"Zhang","year":"2021","journal-title":"Int. J. Med. Sci."},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2202-14-46","article-title":"Physical exercise improves functional recovery through mitigation of autophagy, attenuation of apoptosis and enhancement of neurogenesis after MCAO in rats.","volume":"14","author":"Zhang","year":"2013","journal-title":"BMC Neurosci."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1706","DOI":"10.1161\/STROKEAHA.111.000504","article-title":"MiRNA-424 protects against permanent focal cerebral ischemia injury in mice involving suppressing microglia activation.","volume":"44","author":"Zhao","year":"2013","journal-title":"Stroke"},{"key":"B37","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1007\/s11427-019-9527-3","article-title":"Rab20 is critical for bacterial lipoprotein tolerization-enhanced bactericidal activity in macrophages during bacterial infection.","volume":"63","author":"Zhao","year":"2020","journal-title":"Sci. China Life Sci."},{"key":"B38","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.pharmthera.2018.05.012","article-title":"Advances in stroke pharmacology.","volume":"191","author":"Zhou","year":"2018","journal-title":"Pharmacol. Ther."}],"container-title":["Frontiers in Molecular Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnmol.2022.986710\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T05:35:53Z","timestamp":1666676153000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnmol.2022.986710\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,25]]},"references-count":38,"alternative-id":["10.3389\/fnmol.2022.986710"],"URL":"https:\/\/doi.org\/10.3389\/fnmol.2022.986710","relation":{},"ISSN":["1662-5099"],"issn-type":[{"value":"1662-5099","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,25]]},"article-number":"986710"}}