title: Modulation of H2O2-induced mitogen-activated protein kinases activation and cell death in SK-N-MC cells by EUK134, a salen derivative.
abstract: Alzheimer's disease is a neurodegenerative disorder that is characterized by the accumulation of senile plaques containing amyloid β (Aβ) and neurofibrillary tangles composed of hyperphosphorylated tau protein in the brain. Oxidative stress has been proposed to mediate Aβ-induced neurotoxicity. In that regard, we evaluated the ability of EUK134, a superoxide dismutase and catalase mimics, to protect human neuroblastoma cell line SK-N-MC against H(2)O(2) -induced oxidative stress. Our data clearly indicated that cell death induced by H(2)O(2) was reversed by EUK134. Likewise, lipid peroxidation, caspase-3 activation and intracellular reactive oxygen species formation all returned to control levels following pre-treatments with EUK134. Elevated phosphorylation of mitogen-activated protein kinases (MAPK) induced by H(2)O(2) in SK-N-MC cells was lowered by EUK134 in a dose-dependent manner. In addition, EUK134 decreased expression of pro-apoptotic genes p53 and Bax and enhanced expression of anti-apoptotic Bcl-2 gene. Taken together, these results suggest that EUK134 protects neuronal cells against H(2)O(2) toxicity by attenuating oxidative stress through inhibition of MAPK phosphorylation cascade.
authors.affiliation: Institute of Biochemistry and Biophysics, University of Tehran, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Mohammadi
authors.forename: Razieh
authors.initials: R
authors.lastname: Yazdanparast
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000502:physiology; D000970:Antineoplastic Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D053148:Caspase 3 / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000378:metabolism; D019254:Genes, bcl-2 / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009447:Neuroblastoma / Q000188:drug therapy / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D009942:Organometallic Compounds / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012459:Salicylates / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D000970:Antineoplastic Agents; D000975:Antioxidants; C433928:EUK-134; D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D009942:Organometallic Compounds; D017382:Reactive Oxygen Species; D012459:Salicylates; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D020928:Mitogen-Activated Protein Kinases; D053148:Caspase 3