title: Metabolomic analysis revealed glycylglycine accumulation in astrocytes after methionine enkephalin administration exhibiting neuron protective effects.
abstract: Owing to its unrevealed etiology, multiple sclerosis lacks specific therapies up to now. Experiential administration of methionine enkephalin (MENK) on mouse model improved disease manifestations to some extent. In order to gain more insight on the significance of MENK application, a capillary electrophoresis-mass spectrometry (CE-MS) technique was employed to profile intracellular metabolite fluctuation in 5 astrocytoma cell lines challenged by MENK. The processed data were first evaluated through a bioinformatic process to ensure their compatibility with the study aims and then subjected to multivariate analysis. The results indicated that MENK administration increased intracellular tyrosine, phenylalanine, methionine and glycylglycine. Exemplified by U87 cells, glycylglycine inhibited cell proliferation as well as MENK but it also decreased cell nitric oxide excretion which could not be evoked by MENK. The neuron protective effects were also mirrored by the increased expression of some genes related to remyelination. This study demonstrated CE-MS to be a promising tool for cell metabolomic analysis and benefited the therapeutic exploring of multiple sclerosis with respect to metabolism intervention.
authors.affiliation: Department of Neurology, Shengjing Hospital of China Medical University, 110004 Shenyang, Liaoning, China; Department of Neurology, Dalian (Municipal) Friendship Hospital (Dalian Red Cross Hospital),116001 Dalian, China.
authors.forename: Chungang
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Clinical Laboratory, The Second Hospital of Dalian Medical University, 116023 Dalian, China.
authors.forename: Huijie
authors.initials: H
authors.lastname: Du
authors.affiliation: Department of Endocrinology, Diabetes and Nutrition, Charité Universitätsmedizin, Campus Benjamin Franklin, 12200 Berlin, Germany; Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbrücke, 14558 Nuthetal, Germany.
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.affiliation: CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 116023 Dalian, China; School of Life Sciences and Technology, Dalian University, 116622, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Wang
authors.affiliation: CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 116023 Dalian, China; School of Life Sciences and Technology, Dalian University, 116622, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Tang
authors.affiliation: Personalized Treatment & Diagnosis Research Center, The First Affiliated Hospital of Liaoning Medical University and Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Jinzhou 121001, China.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Personalized Treatment & Diagnosis Research Center, The First Affiliated Hospital of Liaoning Medical University and Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Jinzhou 121001, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Li
authors.affiliation: Personalized Treatment & Diagnosis Research Center, The First Affiliated Hospital of Liaoning Medical University and Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Jinzhou 121001, China.
authors.forename: Qingjun
authors.initials: Q
authors.lastname: Wang
authors.affiliation: CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 116023 Dalian, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Immunology, School of Basic Medical Science, China Medical University, Shenyang 110001, China.
authors.forename: Fengping
authors.initials: F
authors.lastname: Shan
authors.affiliation: Department of Neurology, Shengjing Hospital of China Medical University, 110004 Shenyang, Liaoning, China. Electronic address: fengjuan99@hotmail.com.
authors.forename: Juan
authors.initials: J
authors.lastname: Feng
authors.affiliation: Clinical Laboratory, The Second Hospital of Dalian Medical University, 116023 Dalian, China. Electronic address: xu27002@126.com.
authors.forename: Fang
authors.initials: F
authors.lastname: Xu
authors.affiliation: CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 116023 Dalian, China; Personalized Treatment & Diagnosis Research Center, The First Affiliated Hospital of Liaoning Medical University and Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Jinzhou 121001, China; Clinical Laboratory, Dalian Sixth People's Hospital, Dalian 116031, China. Electronic address: gaop@dicp.ac.cn.
authors.forename: Peng
authors.initials: P
authors.lastname: Gao
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016000:Cluster Analysis; D016207:Cytokines / Q000235:genetics; D019075:Electrophoresis, Capillary; D004744:Enkephalin, Methionine / Q000494:pharmacology*; D006033:Glycylglycine / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D013058:Mass Spectrometry; D055432:Metabolomics / Q000295:instrumentation / Q000379:methods*; D009103:Multiple Sclerosis / Q000378:metabolism; D015999:Multivariate Analysis; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D011957:Receptors, Opioid / Q000378:metabolism
chemical_list: D016207:Cytokines; D018696:Neuroprotective Agents; D011957:Receptors, Opioid; C033593:methionine-enkephalin receptor; D006033:Glycylglycine; D009569:Nitric Oxide; D004744:Enkephalin, Methionine
keywords: Capillary electrophoresis-mass spectrometry; Metabolomics; Methionine enkephalin; Multiple sclerosis