BRG1 alleviates microglial activation by promoting the KEAP1-NRF2/HO-1 signaling pathway and minimizing oxidative damage in cerebral ischemia-reperfusion. 2023

Kongwei Guo, and Yanxing Shang, and Zhao Wang, and Yu Li, and Jinliang Chen, and Baofeng Zhu, and Dongmei Zhang, and Jianrong Chen
Medical Research Center, Affiliated Hospital 2 of Nantong University, Nantong 226001, People's Republic of China; Department of Clinical Medicine, Medical College, Nantong University, Nantong 226001, People's Republic of China; Nantong Key Laboratory of Molecular Immunology, Affiliated Hospital 2 of Nantong University, Nantong 226001, People's Republic of China.

BRG1 is a key factor in the process of apoptosis and oxidative damage; however, its role in the pathophysiology of ischemic stroke is unclear. Here, we discovered that during middle cerebral artery occlusion (MCAO) reperfusion in mice, microglia were significantly activated in the cerebral cortex of the infarct area, and BRG1 expression was increased in the mouse MCAO/R model, peaking at 4 days. In microglia subjected to OGD/R, BRG1 expression increased and peaked at 12 h after reoxygenation. After ischemic stroke, in vitro changing the expression of BRG1 expression levels greatly altered the activation of microglia and the production of antioxidant and pro-oxidant proteins. Knocking down BRG1 expression levels in vitro increased the inflammatory response, promoted microglial activation, and decreased the expression of the NRF2/HO-1 signaling pathway after ischemic stroke. In contrast, overexpression of BRG1 dramatically reduced the expression of NRF2/HO-1 signaling pathway and microglial activation. Our research reveals that BRG1 reduces postischemic oxidative damage via the KEAP1-NRF2/HO-1 signaling pathway, protecting against brain ischemia/reperfusion injury. Using BRG1 as a pharmaceutical target to inhibit inflammatory responses to reduce oxidative damage may be a unique way to explore techniques for the treatment of ischemic stroke and other cerebrovascular illnesses.

UI MeSH Term Description Entries
D002545 Brain Ischemia Localized reduction of blood flow to brain tissue due to arterial obstruction or systemic hypoperfusion. This frequently occurs in conjunction with brain hypoxia (HYPOXIA, BRAIN). Prolonged ischemia is associated with BRAIN INFARCTION. Cerebral Ischemia,Ischemic Encephalopathy,Encephalopathy, Ischemic,Ischemia, Cerebral,Brain Ischemias,Cerebral Ischemias,Ischemia, Brain,Ischemias, Cerebral,Ischemic Encephalopathies
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D000072019 Kelch-Like ECH-Associated Protein 1 An adaptor protein characterized by an N-terminal BTB-POZ DOMAIN and six KELCH REPEATS that functions as a substrate for the E3 UBIQUITIN LIGASE complex. It negatively-regulates NF-E2-RELATED FACTOR 2 by targeting it for ubiquitination and degradation by the PROTEASOME. It also represses genes regulated by ANTIOXIDANT RESPONSE ELEMENTS. KEAP-1 Protein,KEAP1 Protein,KEAP 1 Protein,Kelch Like ECH Associated Protein 1
D000083242 Ischemic Stroke Stroke due to BRAIN ISCHEMIA resulting in interruption or reduction of blood flow to a part of the brain. When obstruction is due to a BLOOD CLOT formed within in a cerebral blood vessel it is a thrombotic stroke. When obstruction is formed elsewhere and moved to block a cerebral blood vessel (see CEREBRAL EMBOLISM) it is referred to as embolic stroke. Wake-up stroke refers to ischemic stroke occurring during sleep while cryptogenic stroke refers to ischemic stroke of unknown origin. Acute Ischemic Stroke,Cryptogenic Embolism Stroke,Cryptogenic Ischemic Stroke,Cryptogenic Stroke,Ischaemic Stroke,Wake-up Stroke,Acute Ischemic Strokes,Cryptogenic Embolism Strokes,Cryptogenic Ischemic Strokes,Cryptogenic Strokes,Embolism Stroke, Cryptogenic,Ischaemic Strokes,Ischemic Stroke, Acute,Ischemic Stroke, Cryptogenic,Ischemic Strokes,Stroke, Acute Ischemic,Stroke, Cryptogenic,Stroke, Cryptogenic Embolism,Stroke, Cryptogenic Ischemic,Stroke, Ischaemic,Stroke, Ischemic,Stroke, Wake-up,Wake up Stroke,Wake-up Strokes
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D015424 Reperfusion Restoration of blood supply to tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. It is primarily a procedure for treating infarction or other ischemia, by enabling viable ischemic tissue to recover, thus limiting further necrosis. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing REPERFUSION INJURY. Reperfusions
D015427 Reperfusion Injury Adverse functional, metabolic, or structural changes in tissues that result from the restoration of blood flow to the tissue (REPERFUSION) following ISCHEMIA. Ischemia-Reperfusion Injury,Injury, Ischemia-Reperfusion,Injury, Reperfusion,Reperfusion Damage,Damage, Reperfusion,Injury, Ischemia Reperfusion,Ischemia Reperfusion Injury,Ischemia-Reperfusion Injuries,Reperfusion Damages,Reperfusion Injuries
D017628 Microglia The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling. Microglial Cell,Cell, Microglial,Microglial Cells,Microglias
D051267 NF-E2-Related Factor 2 A basic-leucine zipper transcription factor that was originally described as a transcriptional regulator controlling expression of the BETA-GLOBIN gene. It may regulate the expression of a wide variety of genes that play a role in protecting cells from oxidative damage. Nfe2l2 Protein,Nuclear Factor (Erythroid-Derived 2)-Like 2 Protein,Nuclear Factor E2-Related Factor 2,NF E2 Related Factor 2,Nuclear Factor E2 Related Factor 2

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