title: Identification of pLG72-Induced Oxidative Stress Using Systemic Approaches.
abstract: G72 is a schizophrenia-susceptible gene encoding a polypeptide with 153 amino acids. In 2002, it was originally proposed as an activator of D-amino acid oxidase (DAOA) that could enhance the activity of DAAO and subsequently reduce the neurotransmission of N-methyl-D-aspartate receptors. However, several controversial findings have been reported recently. Due to a number of inconsistent descriptions of pLG72's biofunctions, this study aims to identify the cellular effects induced by pLG72 in U87 cells using systems biology approaches. The analyses of transcriptomics and biological networks showed that pLG72 might be involved in the induction of oxidative stress. To confirm the in silico prediction, we tested and discovered that overexpression of pLG72 effectively enhanced reactive oxygen species (ROS) in U87 cells and, furthermore, this induction can be quenched by Tempol, a general ROS scavenger. Therefore, G72-transgenic mice presenting some psychiatric symptoms, along with the pLG72 level being significantly increased in the serum of patients with schizophrenia, have led us to propose that the ROS enhancement in mental diseases may be from the overexpression of pLG72 in brain cells.
authors.affiliation: Department of Clinical Laboratory, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310000, China ; Department of Biomedical Sciences Laboratory, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang 322100, China.
authors.forename: Maofeng
authors.initials: M
authors.lastname: Wang
authors.affiliation: Graduate Institute of Basic Medical Science, College of Medicine, China Medical University, Taichung 40402, Taiwan.
authors.forename: Hsi-Ju
authors.initials: HJ
authors.lastname: Chen
authors.affiliation: Department of Clinical Laboratory, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310000, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Internal Medicine, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang 322100, China.
authors.forename: Weimin
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Clinical Laboratory, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310000, China.
authors.forename: Xinyou
authors.initials: X
authors.lastname: Xie
authors.affiliation: Graduate Institute of Basic Medical Science, College of Medicine, China Medical University, Taichung 40402, Taiwan ; Department of Computer Science and Information Engineering, Asia University, Taichung 41354, Taiwan.
authors.forename: Hao-Teng
authors.initials: HT
authors.lastname: Chang
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics*; D002460:Cell Line; D003497:Cyclic N-Oxides / Q000008:administration & dosage; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008822:Mice, Transgenic; D018384:Oxidative Stress / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology; D013113:Spin Labels; D009435:Synaptic Transmission / Q000235:genetics*; D059467:Transcriptome / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D003497:Cyclic N-Oxides; C475071:DAOA protein, human; D047908:Intracellular Signaling Peptides and Proteins; D017382:Reactive Oxygen Species; D016194:Receptors, N-Methyl-D-Aspartate; D013113:Spin Labels; C001803:tempol