title: Sulfiredoxin-1 protects primary cultured astrocytes from ischemia-induced damage.
abstract: Astrocytes appear to be important regulators of the inflammatory events that occur in stroke. Sulfiredoxin-1 (Srxn1), an endogenous antioxidant protein, exhibits neuroprotective effects. Although the mechanism by which Srxn1 negatively regulates oxidative and apoptotic pathways has been extensively characterized, the impact of Srxn1 on inflammation has not been well studied. In this study, we used oxygen-glucose deprivation followed by recovery (OGD/R) and hydrogen peroxide (H2O2) to mimic stress from cerebral ischemic damage on primary cultured astrocytes. We found that knockdown of Srxn1 by two shRNAs resulted in decreased cell viability of astrocytes. Decreased level of Srxn1 also correlated with excessive levels of proinflammatory cytokines and chemokines such as TNF-α, MPO, IL-1β, and IL-6. In addition, Srxn1 appeared to influence the strength of TLR4 signaling pathway; the expression of COX-2, IL-6, and NOS2 were strongly induced by OGD/R and H2O2 in astrocyte cultures with Srxn1-shRNAs. Our results suggested that loss of Srxn1 expression in astrocytes may cause excessive activation of inflammatory responses which contribute to OGD/R- and H2O2-induced cell death. Restoring Srxn1 function by gene therapy and/or pharmacology emerges as a promising strategy for the treatment of stroke and other chronic neurodegenerative diseases.
authors.affiliation: Department of Pathology, Chongqing Medical University, 400016 Chongqing, China; Institute of Neuroscience, Chongqing Medical University, 400016 Chongqing, China; Key Laboratory of Neurobiology, Chongqing Medical University, 400016 Chongqing, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Pathology, Chongqing Medical University, 400016 Chongqing, China; Institute of Neuroscience, Chongqing Medical University, 400016 Chongqing, China; Key Laboratory of Neurobiology, Chongqing Medical University, 400016 Chongqing, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Respiratory Medicine, Jiangjin Center Hospital, 402260, Chongqing, China.
authors.forename: Shipeng
authors.initials: S
authors.lastname: Lei
authors.affiliation: Department of Pathology, Chongqing Medical University, 400016 Chongqing, China; Institute of Neuroscience, Chongqing Medical University, 400016 Chongqing, China; Key Laboratory of Neurobiology, Chongqing Medical University, 400016 Chongqing, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Pathology, Chongqing Medical University, 400016 Chongqing, China; Institute of Neuroscience, Chongqing Medical University, 400016 Chongqing, China; Key Laboratory of Neurobiology, Chongqing Medical University, 400016 Chongqing, China.
authors.forename: Yuanling
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pathology, Chongqing Medical University, 400016 Chongqing, China; Institute of Neuroscience, Chongqing Medical University, 400016 Chongqing, China; Key Laboratory of Neurobiology, Chongqing Medical University, 400016 Chongqing, China.
authors.forename: Yunchuan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Pathology, Chongqing Medical University, 400016 Chongqing, China; Institute of Neuroscience, Chongqing Medical University, 400016 Chongqing, China; Key Laboratory of Neurobiology, Chongqing Medical University, 400016 Chongqing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Pathology, Chongqing Medical University, 400016 Chongqing, China; Institute of Neuroscience, Chongqing Medical University, 400016 Chongqing, China; Key Laboratory of Neurobiology, Chongqing Medical University, 400016 Chongqing, China.
authors.forename: Jingxian
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Pathology, Chongqing Medical University, 400016 Chongqing, China; Institute of Neuroscience, Chongqing Medical University, 400016 Chongqing, China; Key Laboratory of Neurobiology, Chongqing Medical University, 400016 Chongqing, China. Electronic address: zhaoyong668@cqmu.edu.cn.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology*; D015687:Cell Hypoxia / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D005947:Glucose / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000633:toxicity; D066298:In Vitro Techniques; D007249:Inflammation; D009419:Nerve Tissue Proteins / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000235:genetics; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D010100:Oxygen / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis / Q000235:genetics
chemical_list: D018925:Chemokines; D016207:Cytokines; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D006861:Hydrogen Peroxide; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D050862:Oxidoreductases Acting on Sulfur Group Donors; C542495:Srxn1 protein, rat; D005947:Glucose; D010100:Oxygen
keywords: Astrocytes; Inflammation; Ischemia; Sulfiredoxin-1