title: ROS/TXNIP pathway contributes to thrombin induced NLRP3 inflammasome activation and cell apoptosis in microglia.
abstract: There is no effective therapy for intracerebral hemorrhage (ICH) because of poor understanding of the mechanisms of brain injury after hemorrhage. The NLRP3 inflammasome, as a vital component of innate immune system, which is associated with a wide range of human CNS disorders, including ICH. But its detailed mechanisms in ICH remain mainly unclear. In this study, BV2 cells with thrombin exposure were used to investigate the role of NLRP3 inflammasome in thrombin-induced brain injury. We used western blot to detect NLRP3 inflammasome activation and the expression of thioredoxin binding protein (TXNIP), DCFH-DA to investigate intracellular reactive oxygen species (ROS), flow cytometry to analyze apoptosis. Our results showed that ROS inhibitor N-acetyl-l-cysteine (NAC) suppressed the upregulation of intracellular ROS and TXNIP expression. Furthermore, the cell apoptosis and expression of apoptotic protein were significantly attenuated after treatment of thrombin with NAC or NLRP3 antagonist (MCC950). Thrombin activates ROS/TXNIP/NLRP3 signaling in BV2 cells, which may indicate a mechanism that pro-inflammatory and pro-apoptotic contributes to the development of ICH.
authors.affiliation: Xuzhou Medical University, Xuzhou, Jiangsu Province, China; Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China.
authors.forename: Xinchun
authors.initials: X
authors.lastname: Ye
authors.affiliation: Xuzhou Medical University, Xuzhou, Jiangsu Province, China; Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Zuo
authors.affiliation: Xuzhou Medical University, Xuzhou, Jiangsu Province, China; Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Yu
authors.affiliation: Xuzhou Medical University, Xuzhou, Jiangsu Province, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Xuzhou Medical University, Xuzhou, Jiangsu Province, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China.
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Cui
authors.affiliation: Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Bao
authors.affiliation: Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Zan
authors.affiliation: Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China.
authors.forename: Zuohui
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zu
authors.affiliation: Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China.
authors.forename: Hongjuan
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China. Electronic address: guiyuncui@foxmail.com.
authors.forename: Guiyun
authors.initials: G
authors.lastname: Cui
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D005434:Flow Cytometry; D016166:Free Radical Scavengers / Q000494:pharmacology; D058847:Inflammasomes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013879:Thioredoxins / Q000378:metabolism*; D013917:Thrombin / Q000494:pharmacology*; D013997:Time Factors; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494827:Bax protein, mouse; D002352:Carrier Proteins; D016166:Free Radical Scavengers; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; C445672:Txnip protein, mouse; D051028:bcl-2-Associated X Protein; D013879:Thioredoxins; D013917:Thrombin; D053148:Caspase 3; D000111:Acetylcysteine
keywords: Apoptosis; ICH; NLRP3 inflammasome; ROS/TXNIP pathway; Thrombin