دورية أكاديمية
أعرض في EDS

Rab27a-dependent exosomes protect against cerebral ischemic injury by reducing endothelial oxidative stress and apoptosis.

التفاصيل البيبلوغرافية
العنوان: Rab27a-dependent exosomes protect against cerebral ischemic injury by reducing endothelial oxidative stress and apoptosis.
المؤلفون: Ma X; Guangdong Key Laboratory of Age-related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China., Zhao J; Emergency Department, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China., Li S; Guangdong Key Laboratory of Age-related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China., Wang Y; Guangdong Key Laboratory of Age-related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.; Institute of Biochemistry and Molecular Biology, Guangdong Medical University, Zhanjiang, China., Liu J; Guangdong Key Laboratory of Age-related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China., Shi Y; Guangdong Key Laboratory of Age-related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China., Liu J; Guangdong Key Laboratory of Age-related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China., Chen Y; Guangdong Key Laboratory of Age-related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China., Chen Y; Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, Ohio, USA., Pan Q; Guangdong Key Laboratory of Age-related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
المصدر: CNS neuroscience & therapeutics [CNS Neurosci Ther] 2022 Oct; Vol. 28 (10), pp. 1596-1612. Date of Electronic Publication: 2022 Jun 29.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 101473265 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1755-5949 (Electronic) Linking ISSN: 17555930 NLM ISO Abbreviation: CNS Neurosci Ther Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Oxford, UK : Wiley-Blackwell, c2008-
مواضيع طبية MeSH: Brain Injuries*/metabolism , Exosomes*/metabolism , rab27 GTP-Binding Proteins*/genetics , rab27 GTP-Binding Proteins*/metabolism, Animals ; Apoptosis ; Caspase 3/metabolism ; Endothelial Cells/metabolism ; Infarction, Middle Cerebral Artery/complications ; Mice ; Oxidative Stress ; Oxygen ; Reactive Oxygen Species/metabolism
مستخلص: Introduction: Multicellular crosstalk within the brain tissue has been suggested to play a critical role in maintaining cerebral vascular homeostasis. Exosomes (EXs) mediated cell-cell communication, but its role in cerebral ischemic injury is largely unknown. Rab27a is one of the major genes controlling EX release. Here, we explored the role of Rab27a in regulating brain EXs secretion, and the effects of Rab27a-mediated EXs on ischemia evoked cerebral vascular disruption and brain injury.
Methods: Cerebral ischemia was induced in Rab27a knockout (Rab27a -/- ) and wide type (WT) mice by transient middle cerebral artery occlusion (tMCAO). Differential gene expression analysis was performed in ischemic brain tissue by using mRNA sequencing. EXs isolated from brain tissue of Rab27a -/- and WT mice (EX WT or EX Rab27a-/- ) were pre-administrated into tMCAO operated Rab27a -/- mice or oxygen and glucose deprivation (OGD) treated primary brain vascular endothelial cells (ECs).
Results: We demonstrated that Rab27a expression in the peri-infarct area of brain was significantly elevated, which was associated with local elevation in EXs secretion. Rab27a deficiency dramatically decreased the level of EXs in brain tissue of normal and tMCAO-treated mice, and Rab27a -/- mice displayed an increase in infarct volume and NDS, and a decrease in cMVD and CBF following tMCAO. Pre-infusion of EX WT increased the brain EXs levels in the tMCAO operated Rab27a -/- mice, accompanied with an increase in cMVD and CBF, and a decrease in infarct volume, NDS, ROS production, and apoptosis. The effects of EX Rab27a-/- infusion were much diminished although in a dose-dependent manner. In OGD-treated ECs, EX Rab27a-/- showed less effectivity than EX WT in decreasing ROS overproduction and apoptosis, paralleling with down-regulated expression of NOX2 and cleaved caspase-3.
Conclusion: Our study demonstrates that Rab27a controls brain EXs secretion and functions, contributing to cerebral vascular protection from ischemic insult by preventing oxidative stress and apoptosis via down-regulating NOX2 and cleaved caspase-3 expression.
(© 2022 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)
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فهرسة مساهمة: Keywords: Rab27a; apoptosis; exosomes; ischemic stroke; oxidative stress
المشرفين على المادة: 0 (Reactive Oxygen Species)
0 (rab27 GTP-Binding Proteins)
EC 3.4.22.- (Caspase 3)
EC 3.6.1.-. (Rab27a protein, mouse)
S88TT14065 (Oxygen)
تواريخ الأحداث: Date Created: 20220630 Date Completed: 20220908 Latest Revision: 20221031
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC9437240
DOI: 10.1111/cns.13902
PMID: 35770324
قاعدة البيانات: MEDLINE
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