title: Edaravone leads to proteome changes indicative of neuronal cell protection in response to oxidative stress.
abstract: Neuronal cell death, in neurodegenerative disorders, is mediated through a spectrum of biological processes. Excessive amounts of free radicals, such as reactive oxygen species (ROS), has detrimental effects on neurons leading to cell damage via peroxidation of unsaturated fatty acids in the cell membrane. Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) has been used for neurological recovery in several countries, including Japan and China, and it has been suggested that Edaravone may have cytoprotective effects in neurodegeneration. Edaravone protects nerve cells in the brain by reducing ROS and inhibiting apoptosis. To gain further insight into the cytoprotective effects of Edaravone against oxidative stress condition we have performed comparative two-dimensional gel electrophoresis (2DE)-based proteomic analyses on SH-SY5Y neuroblastoma cells exposed to oxidative stress and in combination with Edaravone. We showed that Edaravone can reverse the cytotoxic effects of H2O2 through its specific mechanism. We observed that oxidative stress changes metabolic pathways and cytoskeletal integrity. Edaravone seems to reverse the H2O2-mediated effects at both the cellular and protein level via induction of Peroxiredoxin-2.
authors.affiliation: Department of Biological Sciences, St John's University, New York, NY, USA; Cellular and Molecular Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran. Electronic address: sjamif@gmail.com.
authors.forename: Mohammad-Saeid
authors.initials: MS
authors.lastname: Jami
authors.affiliation: Department of Biological Sciences, St John's University, New York, NY, USA. Electronic address: Zahra.salehi@live.com.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Salehi-Najafabadi
authors.affiliation: Cellular and Molecular Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran. Electronic address: Fereshte.ahmadi86@ymail.com.
authors.forename: Fereshteh
authors.initials: F
authors.lastname: Ahmadinejad
authors.affiliation: Kimmel Center for Biology and Medicine at the Skirball Institute and Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY, USA. Electronic address: Esthelle.Hoedt@med.nyu.edu.
authors.forename: Esthelle
authors.initials: E
authors.lastname: Hoedt
authors.affiliation: Cellular and Molecular Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran. Electronic address: mchalesh@yahoo.com.
authors.forename: Morteza Hashemzadeh
authors.initials: MH
authors.lastname: Chaleshtori
authors.affiliation: Cellular and Molecular Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran.
authors.forename: Mahdi
authors.initials: M
authors.lastname: Ghatrehsamani
authors.affiliation: Kimmel Center for Biology and Medicine at the Skirball Institute and Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY, USA. Electronic address: Thomas.Neubert@med.nyu.edu.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Neubert
authors.affiliation: The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Norway. Electronic address: jpl@sus.no.
authors.forename: Jan Petter
authors.initials: JP
authors.lastname: Larsen
authors.affiliation: Department of Biological Sciences, St John's University, New York, NY, USA; The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Norway. Electronic address: mollers@stjohns.edu.
authors.forename: Simon Geir
authors.initials: SG
authors.lastname: Møller
mesh_terms: D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D020543:Proteome / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D020543:Proteome; D017382:Reactive Oxygen Species; D000077553:Edaravone; D000983:Antipyrine
keywords: Edaravone; Oxidative stress; Parkinson's disease; Peroxiredoxin-2; Proteomics; l-Dopa