title: SK-N-MC cell death occurs by distinct molecular mechanisms in response to hydrogen peroxide and superoxide anions: involvements of JAK2-STAT3, JNK, and p38 MAP kinases pathways.
abstract: Oxidative stress plays a vital role in the pathogenesis of neurodegenerative diseases. Nerve cells are incessantly exposed to environmental stresses leading to overproduction of some harmful species like reactive oxygen species (ROS). ROS including hydrogen peroxide and superoxide anion are potent inducers of various signaling pathways encompassing MAPKs and JAK-STAT pathways. In the current study, we scrutinized the effects of hydrogen peroxide and/or menadione (superoxide anion generator) on JNK/p38-MAPKs and JAK2-STAT3 pathways to elucidate the mechanism(s) by which each oxidant modulated the above-mentioned pathways leading to SK-N-MC cell death. Our results delineated that hydrogen peroxide and superoxide anion radical induced distinct responses as we showed that STAT3 and p38 were activated in response to hydrogen peroxide, but not superoxide anion radicals indicating the specificity in ROS-induced signaling pathways activations and behaviors. We also observed that menadione induced JNK-dependent p53 expression and apoptotic death in SK-N-MC cells while H2O2-induced JNK activation was p53 independent. Thus, we declare that ROS type has a key role in selective instigation of JNK/p38-MAPKs and JAK2-STAT3 pathways in SK-N-MC cells. Identifying these differential behaviors and mechanisms of hydrogen peroxide and superoxide anion functions illuminates the possible therapeutic targets in the prevention or treatment of ROS-induced neurodegenerative diseases such as Alzheimer's disease.
authors: Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
authors: Maryam
authors: M
authors: Moslehi
authors: Razieh
authors: R
authors: Yazdanparast
mesh_terms: D002374:Catalase / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D050050:Protein Carbonylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D013481:Superoxides / Q000494:pharmacology*; D013997:Time Factors; D024483:Vitamin K 3 / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D016877:Oxidants; D047428:Protein Kinase Inhibitors; D050796:STAT3 Transcription Factor; D013481:Superoxides; D024483:Vitamin K 3; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D053614:Janus Kinase 2; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases