Irisin Ameliorates Hypoxia/Reoxygenation-Induced Inflammation and Apoptosis in PC12 Cells by Inhibiting TLR4/MYD88 Signaling Pathway

2019 ◽  
Vol 17 (3) ◽  
pp. 329-336
Author(s):  
Wang Jinli ◽  
Xu Fenfen ◽  
Zheng Yuan ◽  
Cheng Xu ◽  
Zhang Piaopiao ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Signaling Pathway ◽  
Pc12 Cells ◽  
Major Complication ◽  
Lactic Dehydrogenase ◽  
Dependent Manner ◽  
Cerebral Ischemic Stroke ◽  
Cerebral Ischemic ◽  
Myd88 Signaling ◽  
Hypoxia Reoxygenation

Cardiovascular disease including cerebral ischemic stroke is the major complication that increases the morbidity and mortality in patients with diabetes mellitus as much as four times. It has been well established that irisin, with its ability to regulate glucose and lipid homeostasis as well as anti-inflammatory and anti-apoptotic properties, has been widely examined for its therapeutic potentials in managing metabolic disorders. However, the mechanism of irisin in the regulation of cerebral ischemic stroke remains unclear. Using PC12 cells as a model, we have shown that hypoxia/reoxygenation inhibits cell viability and increases lactic dehydrogenase. Irisin, in a dose-dependent manner, reversed these changes. The increase in inflammatory mediators (IL-1β, IL-6, and TNF-α) by hypoxia/reoxygenation was reversed by irisin. Furthermore, the cell apoptosis promoted by hypoxia/reoxygenation was also inhibited by irisin. Irisin suppressed TLR4/MyD88 signaling pathway leading to amelioration of inflammation and apoptosis in PC12 cells. Thus, inhibition of TLR4/MyD88 signaling pathway via irisin could be an important mechanism in the regulation of hypoxia/reoxygenation-induced inflammation and apoptosis in PC12 cells.

scholarly journals Based on Dll4/Notch1 Signaling Pathway to Elucidate the Therapeutic Effect and Mechanism of L-borneolum on Cerebral Ischemic Stroke Rats

2021 ◽  
Author(s):  
Taiwei Dong ◽  
Nian Chen ◽  
Rong Ma ◽  
Qian Xie ◽  
Xiaoqing Guo ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Signaling Pathway ◽  
Caspase 3 ◽  
Neurological Function ◽  
Immunohistochemical Method ◽  
Research Progress ◽  
Notch1 Signaling ◽  
Cerebral Ischemic Stroke ◽  
Cerebral Ischemic ◽  
Notch1 Signaling Pathway

Abstract Background: The current research progress suggests that a single therapy may not be ideal means for complex cerebral ischemic stoke (CIS). l-Borneolum is the crystallization of fresh leaves of Blumea balsamifera (L.) DC, we have found that l-borneolum plays a best anti-cerebral ischemic effect than d-borneolum or synthetic borneolum. However, the mechanism is needed to be explored in depth. Therefore, based on comprehensive approach that combines molecular docking technology and molecular biology, this stiudy aimed to investigate the potential mechanism of l-borneolum on CIS rats and provide scientific evidence for the treatment of l-borneolum in CIS.Methods: Cerebral ischemic stroke (CIS) rats with permanent middle cerebral artery occlusion (pMCAO) were applied to this study. The modified neurological severity scores (mNSS) and Longa neurological function scoring methods were used to assess the neurobehavioral scores. 2,3,5-Triphenyltetrazolium chloride (TTC) staining and hematoxylin-eosin (HE) staining were used to evaluate pathological changes of cerebral tissue. Ultrastructure of cortical capillary and blood-brain barrier (BBB) in rats were observed by transmission electron microscopy. In addition, the protein expression of Notch1, Dll4, Hey1, Hes1, Hes5, VEGFA and p65 in the cortex of rats were determined by Western blotting (WB). The protein contents of Caspase 3 in the cortex of rats were determined by immunohistochemical method (IHC). Results: l-Borneolum could prolong the resuscitation time, reduce the abnormal increased rectal temperature, improve neurological function in a dose-dependently. Additionally, l-borneolum could significantly alleviate brainstem edema and inflammation, as well as improve the ultrastructure of capillary and BBB in cortex. Moreover, 0.2 g/kg l-borneolum could substantially decrease the protein expressions of Dll4, Notch1, Hes1, Hes5, and VEGFA in the cortex while it decreased the level of Caspase-3 in the cortex of rats. Conclusions: l-Borneolum could repair neurological function by regulating Dll4/Notch1 signaling pathway, l-borneolum might be a good complementary agent for CIS.

scholarly journals TGF-β1/Smad3 Signaling Pathway Suppresses Cell Apoptosis in Cerebral Ischemic Stroke Rats

2017 ◽  
Vol 23 ◽  
pp. 366-376 ◽  
Author(s):  
Haiping Zhu ◽  
Qunfeng Gui ◽  
Xiaobo Hui ◽  
Xiaodong Wang ◽  
Jian Jiang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Cerebral Ischemic Stroke ◽  
Cerebral Ischemic ◽  
Tgf Β1

MicroRNA-384-5p Promotes Endothelial Progenitor Cell Proliferation and Angiogenesis in Cerebral Ischemic Stroke through the Delta-Likeligand 4-Mediated Notch Signaling Pathway

2020 ◽  
Vol 49 (1) ◽  
pp. 39-54 ◽  
Author(s):  
Jia Fan ◽  
Weiwei Xu ◽  
Shanji Nan ◽  
Meiji Chang ◽  
Yizhi Zhang
Keyword(s):  
Cell Proliferation ◽  
Ischemic Stroke ◽  
Infarct Size ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Notch Signaling Pathway ◽  
Brain Infarct ◽  
Cerebral Ischemic Stroke ◽  
Cerebral Ischemic

Background: MicroRNAs (miRs) have a crucial regulatory role in endothelial cell function and tumor angiogenesis by inhibiting the expressions of their target genes. The participation of microRNA-384-5p (miR-384-5p) has been prominently reported in various ischemia-induced diseases such as myocardial ischemia and atherosclerosis. Hence, the present study aimed at exploring the effect of miR-384-5p on proliferation, apoptosis, and angiogenesis of endothelial progenitor cells (EPCs) in cerebral ischemic stroke and investigating the associated underlying mechanism. Methods: A middle cerebral artery occlusion (MCAO) mouse model was established, with determination of the expression of cluster of differentiation 31 (CD31) and vascular endothelial growth factor (VEGF) proteins. Next, the MCAO mice and EPCs separated from MCAO mice were injected or transfected with mimics or inhibitors of miR-384-5p, or small interference RNA Delta-likeligand 4 (si-DLL4) in order to evaluate their effect on brain infarct size, cell proliferation, apoptosis, and angiogenesis. The relationship among miR-384-5p, DLL4, and the Notch signaling pathway was then verified by a series of experiments. Results: In MCAO mice, an increased brain infarct size and cell apoptosis in brain tissues were evident, with decreased expression of miR-384-5p, VEGF, and CD31, as well as increased DLL4 expression. After miR-384-5p mimic or si-DLL4 treatment, the brain infarct size and cell apoptosis in the brain tissues were reduced in compliance with an increased expression of VEGF and CD31. Our findings demonstrated that miR-384-5p negatively regulated the expression of DLL4, which further downregulated the Notch signaling pathway. When miR-384-5p was overexpressed or DLL4 silenced, the cell proliferation and angiogenesis of EPCs were promoted and cell apoptosis was inhibited. Conclusions: Our study demonstrated that overexpressed miR-384-5p targeting DLL4 could stimulate proliferation and angiogenesis, while inhibiting apoptosis of EPCs in mice with cerebral ischemic stroke through the Notch signaling pathway.

scholarly journals A Network Pharmacology-Based Identification Study on the Mechanism of Xiao-Xu-Ming Decoction for Cerebral Ischemic Stroke

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
De-Hui Li ◽  
Yi-Fan Su ◽  
Chun-Xia Sun ◽  
Huan-Fang Fan ◽  
Wei-Juan Gao
Keyword(s):  
Ischemic Stroke ◽  
Signaling Pathway ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Signal Pathways ◽  
Biological Processes ◽  
Active Ingredients ◽  
Cerebral Ischemic Stroke ◽  
Cerebral Ischemic ◽  
Mannose Metabolism

Objective. We used the network pharmacological analysis method to explore the mechanism of multicomponent, multitarget, and multiway actions of Xiao-Xu-Ming decoction (XXMD) for cerebral ischemic stroke (CIS), which provided a basis on the research of innovative drugs. Method. We used the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) to retrieve the active ingredients and targets of 12 herbs of XXMD; we used the Gene Expression Omnibus (GEO) database of the National Center for Biotechnology Information (NCBI) to screen for differentially expressed genes in CIS to obtain the disease targets of CIS and to intersect it with the action targets of XXMD, and then the target drug efficacy is obtained. We used Cytoscape 3.6 software to construct the drug-active ingredient-action target interaction network of XXMD to treat CIS and conduct protein-protein interaction (PPI) network and topology analysis. The action target Gene Ontology (GO) biological processes and metabolic pathways in Kyoto Encyclopedia of Genes and Genomes (KEGG) of XXMD to treat CIS were enrichment analyzed with R software. Result. We screened out 226 active ingredients and 3646 action targets for XXMD. Among them, XXMD to treat CIS has 144 active ingredients, 12 targets, and proteins in the core network of PPI having STAT3, HIF1A, etc. Pathway enrichment analysis was based on the GO and KEGG biological processes involved in active oxygen metabolism, smooth muscle cell proliferation, cytokine production, angiogenesis, redox coenzyme metabolism, and oxidative stress. The main action processes are significantly associated with CIS signal pathways involved in microRNAs, ovarian steroid hormones, NF-кB signaling pathway, Th17 cell differentiation pathway, HIF-1 signaling pathway, folic acid synthesis pathway, galactose metabolism, and fructose and mannose metabolism. Conclusion. This study initially clarified the main targets and pathways of XXMD in the treatment of CIS, which can lay the foundation for further research on its pharmacological effects.

scholarly journals CTRP1 Attenuates Cerebral Ischemia/Reperfusion Injury via the PERK Signaling Pathway

2021 ◽  
Vol 9 ◽  
Author(s):  
Huizhi Fei ◽  
Pu Xiang ◽  
Wen Luo ◽  
Xiaodan Tan ◽  
Chao Gu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Signaling Pathway ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury ◽  
Cerebral Ischemic Stroke ◽  
Cerebral Ischemic

Cerebral ischemic stroke is one of the leading causes of death worldwide. Previous studies have shown that circulating levels of CTRP1 are upregulated in patients with acute ischemic stroke. However, the function of CTRP1 in neurons remains unclear. The purpose of this study was to explore the role of CTRP1 in cerebral ischemia reperfusion injury (CIRI) and to elucidate the underlying mechanism. Middle cerebral artery occlusion/reperfusion (MCAO/R) and oxygen–glucose deprivation/reoxygenation (OGD/R) models were used to simulate cerebral ischemic stroke in vivo and in vitro, respectively. CTRP1 overexpression lentivirus and CTRP1 siRNA were used to observe the effect of CTRP1 expression, and the PERK selective activator CCT020312 was used to activate the PERK signaling pathway. We found the decreased expression of CTRP1 in the cortex of MCAO/R-treated rats and OGD/R-treated primary cortical neurons. CTRP1 overexpression attenuated CIRI, accompanied by the reduction of apoptosis and suppression of the PERK signaling pathway. Interference with CTRP1 expression in vitro aggravated apoptotic activity and increased the expression of proteins involved in the PERK signaling pathway. Moreover, activating the PERK signaling pathway abolished the protective effects of CTRP1 on neuron injury induced by CIRI in vivo and in vitro. In conclusion, CTRP1 protects against CIRI by reducing apoptosis and endoplasmic reticulum stress (ERS) through inhibiting the PERK-dependent signaling pathway, suggesting that CTRP1 plays a crucial role in the pathogenesis of CIRI.

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