title: Effect of N-n-butyl haloperidol iodide on ROS/JNK/Egr-1 signaling in H9c2 cells after hypoxia/reoxygenation.
abstract: Reactive oxygen species (ROS)-induced oxidative stress in cells is an important pathophysiological process during myocardial ischemia/reperfusion (I/R) injury, and the transcription factor Egr-1 is a master switch for various damage pathways during reperfusion injury. An in vitro model of myocardial I/R injury and H9c2 cardiomyoblast cells hypoxia/reoxygenation (H/R) was used to assess whether there is abnormal intracellular ROS/JNK/Egr-1 signaling. We also assessed whether N-n-butyl haloperidol (F2), which exerts protective effects during myocardial I/R injury, can modulate this pathway. H/R induced ROS generation, JNK activation, and increased the expression of Egr-1 protein in H9c2 cells. The ROS scavengers edaravone (EDA) and N-acetyl-L-cysteine (NAC) reduced ROS level, downregulated JNK activation, and Egr-1 expression in H9c2 cells after H/R. The JNK inhibitor SP600125 inhibited Egr-1 overexpression in H9c2 cells caused by H/R. F2 could downregulate H/R-induced ROS level, JNK activation, and Egr-1 expression in H9c2 cells in a dose-dependent manner. The ROS donor hypoxanthine-xanthine oxidase (XO/HX) and the JNK activator ANISO antagonized the effects of F2. Therefore, H/R activates ROS/Egr-1 signaling pathway in H9c2 cells, and JNK activation plays an important role in this pathway. F2 regulates H/R-induced ROS/JNK/Egr-1 signaling, which might be an important mechanism by which it antagonizes myocardial I/R injury.
authors.affiliation: Department of Pharmacology, Shantou University Medical College, Shantou 515041, Guangdong, China.
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Shantou University Medical College, Shantou 515041, Guangdong, China.
authors.forename: Han
authors.initials: H
authors.lastname: Liao
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California 90033, USA.
authors.forename: Shuping
authors.initials: S
authors.lastname: Zhong
authors.affiliation: Department of Pharmacology, Shantou University Medical College, Shantou 515041, Guangdong, China.
authors.forename: Fenfei
authors.initials: F
authors.lastname: Gao
authors.affiliation: Department of Pharmacology, Shantou University Medical College, Shantou 515041, Guangdong, China.
authors.forename: Yicun
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, Shantou University Medical College, Shantou 515041, Guangdong, China.
authors.forename: Zhanqin
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Pharmacology, Shantou University Medical College, Shantou 515041, Guangdong, China.
authors.forename: Shishi
authors.initials: S
authors.lastname: Lu
authors.affiliation: Department of Pharmacology, Shantou University Medical College, Shantou 515041, Guangdong, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Sun
authors.affiliation: Department of Pharmacology, Shantou University Medical College, Shantou 515041, Guangdong, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Analytical Cytology Laboratory, Shantou University Medical College, Shantou 515041, Guangdong, China.
authors.forename: Weiqiu
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Shantou University Medical College, Shantou 515041, Guangdong, China.
authors.forename: Han
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Pharmacy, the First Affiliated Hospital, Shantou University Medical College, Shantou 515041, Guangdong, China.
authors.forename: Fuchun
authors.initials: F
authors.lastname: Zheng
authors.affiliation: 1] Department of Pharmacology, Shantou University Medical College, Shantou 515041, Guangdong, China [2] Department of Cardiovascular Diseases, the First Affiliated Hospital, Shantou University Medical College, Shantou 515041, Guangdong, China.
authors.forename: Ganggang
authors.initials: G
authors.lastname: Shi
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage; D000983:Antipyrine / Q000008:administration & dosage / Q000031:analogs & derivatives; D015687:Cell Hypoxia / Q000187:drug effects; D002460:Cell Line; D051766:Early Growth Response Protein 1 / Q000096:biosynthesis* / Q000235:genetics; D000077553:Edaravone; D005786:Gene Expression Regulation / Q000187:drug effects; D006220:Haloperidol / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000096:biosynthesis* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism
chemical_list: C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; C482574:N-n-butyl haloperidol iodide; D017382:Reactive Oxygen Species; D014969:Xanthine Oxidase; D048670:MAP Kinase Kinase 4; D006220:Haloperidol; D000077553:Edaravone; D000983:Antipyrine; D000111:Acetylcysteine