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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.
Cell Biochem Biophys. 2013 Jul; 66(3):817-29.CB

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+Show Affiliations

Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23417568

Citation

Moslehi, Maryam, and Razieh Yazdanparast. "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." Cell Biochemistry and Biophysics, vol. 66, no. 3, 2013, pp. 817-29.
Moslehi M, Yazdanparast R. 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. Cell Biochem Biophys. 2013;66(3):817-29.
Moslehi, M., & Yazdanparast, R. (2013). 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. Cell Biochemistry and Biophysics, 66(3), 817-29. https://doi.org/10.1007/s12013-013-9526-7
Moslehi M, Yazdanparast R. 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. Cell Biochem Biophys. 2013;66(3):817-29. PubMed PMID: 23417568.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Moslehi,Maryam, AU - Yazdanparast,Razieh, PY - 2013/2/19/entrez PY - 2013/2/19/pubmed PY - 2014/3/4/medline SP - 817 EP - 29 JF - Cell biochemistry and biophysics JO - Cell Biochem Biophys VL - 66 IS - 3 N2 - 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. SN - 1559-0283 UR - https://www.unboundmedicine.com/medline/citation/23417568/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_ L2 - https://dx.doi.org/10.1007/s12013-013-9526-7 DB - PRIME DP - Unbound Medicine ER -