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: Xinchun Ye, Dandan Zuo, Lu Yu, Liang Zhang, Jiao Tang, Chengcheng Cui, Lei Bao, Kun Zan, Zuohui Zhang, Xinxin Yang, Hao Chen, Hai Tang, Jie Zu, Hongjuan Shi, Guiyun Cui
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 485 Issue 2 Pg. 499-505 (04 01 2017) ISSN: 1090-2104 [Electronic] United States
• PMID: 28202418 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Bax protein, mouse
• Carrier Proteins
• Free Radical Scavengers
• Inflammasomes
• NLR Family, Pyrin Domain-Containing 3 Protein
• Nlrp3 protein, mouse
• Proto-Oncogene Proteins c-bcl-2
• Reactive Oxygen Species
• Txnip protein, mouse
• bcl-2-Associated X Protein
• Thioredoxins
• Thrombin
• Caspase 3
• Acetylcysteine

Topics

• Acetylcysteine (pharmacology)
• Animals
• Apoptosis (drug effects)
• Blotting, Western
• Carrier Proteins (metabolism)
• Caspase 3 (metabolism)
• Cell Line
• Flow Cytometry
• Free Radical Scavengers (pharmacology)
• Inflammasomes (drug effects, metabolism)
• Mice
• Microglia (cytology, drug effects, metabolism)
• NLR Family, Pyrin Domain-Containing 3 Protein (metabolism)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Reactive Oxygen Species (metabolism)
• Signal Transduction (drug effects)
• Thioredoxins (metabolism)
• Thrombin (pharmacology)
• Time Factors
• bcl-2-Associated X Protein (metabolism)