title: Ethanol directly induced HMGB1 release through NOX2/NLRP1 inflammasome in neuronal cells.
abstract: It has been reported that ethanol contributes to neuronal damage. However, the mechanisms mediating the actions of ethanol on neurons remain elusive. The present study was designed to test whether ethanol directly induced HMGB1 release and to explore the cellular and molecular mechanism mediating its action. It was found that ethanol increased significant HMGB1 release from SH-SY5Y cells and from cultured primary cortical neurons as detected by ELISA assay. Meanwhile, ethanol induced the expression of NOX2 subunits such as gp91 and p47(phox) and increased the activation of NLRP1 inflammasome. However, when cells were pretreated with NADPH oxidase inhibitor, apocynin, HMGB1 release was significantly decreased. Moreover, apocynin also prevented the activation of NLRP1 inflammasome as detected the levels of cleaved caspase-1. In addition, z-YVAD-fmk, an inhibitor of caspase-1, decreased the ethanol-induced HMGB1 release. It is concluded that ethanol-induced HMGB1 release is associated with NOX2/NLRP1 inflammasome signaling, which represents a novel mechanism of ethanol-associated neuron injury.
authors.affiliation: Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; The Institute of Brain Research, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Guangpin
authors.initials: G
authors.lastname: Chu
authors.affiliation: Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Yinan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Hanjing
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Man
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Tian
authors.affiliation: Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; The Institute of Brain Research, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: xfmeng@mails.tjmu.edu.cn.
authors.forename: Xianfang
authors.initials: X
authors.lastname: Meng
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D020170:Caspase 1 / Q000378:metabolism; D061945:Caspase Inhibitors / Q000494:pharmacology; D045744:Cell Line, Tumor; D000431:Ethanol / Q000633:toxicity*; D024243:HMGB1 Protein / Q000378:metabolism*; D006801:Humans; D058847:Inflammasomes / Q000187:drug effects* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000070576:NLR Proteins; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D061945:Caspase Inhibitors; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; C104200:Hbp1 protein, rat; D058847:Inflammasomes; D008562:Membrane Glycoproteins; D000070576:NLR Proteins; C427903:NLRP1 protein, human; D009419:Nerve Tissue Proteins; C526260:Nlrp1a protein, rat; D017382:Reactive Oxygen Species; D000431:Ethanol; C056558:CYBB protein, human; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D020170:Caspase 1
keywords: Ethanol; HMGB1 release; NLRP1 inflammasome; NOX2