Tags

Type your tag names separated by a space and hit enter

Modulation of notch signaling pathway to prevent H2O2/menadione-induced SK-N-MC cells death by EUK134.
Cell Mol Neurobiol. 2014 Oct; 34(7):1037-45.CM

Abstract

The brain in Alzheimer's disease is under increased oxidative stress, and this may have a role in the pathogenesis and neural death in this disorder. It has been verified that numerous signaling pathways involved in neurodegenerative disorders are activated in response to reactive oxygen species (ROS). EUK134, a synthetic salen-manganese antioxidant complex, has been found to possess many interesting pharmacological activities awaiting exploration. The present study is to characterize the role of Notch signaling in apoptotic cell death of SK-N-MC cells. The cells were treated with hydrogen peroxide (H2O2) or menadione to induce oxidative stress. The free-radical scavenging capabilities of EUK134 were studied through the MTT assay, glutathione peroxidase (GPx) enzyme activity assay, and glutathione (GSH) Levels. The extents of lipid peroxidation, protein carbonyl formation, and intracellular ROS levels, as markers of oxidative stress, were also studied. Our results showed that H2O2/menadione reduced GSH levels and GPx activity. However, EUK134 protected cells against ROS-induced cell death by down-regulation of lipid peroxidation and protein carbonyl formation as well as restoration of antioxidant enzymes activity. ROS induced apoptosis and increased NICD and HES1 expression. Inhibition of NICD production proved that Notch signaling is involved in apoptosis through p53 activation. Moreover, H2O2/menadione led to Numb protein down-regulation which upon EUK134 pretreatment, its level increased and subsequently prevented Notch pathway activation. We indicated that EUK134 can be a promising candidate in designing natural-based drugs for ROS-induced neurodegenerative diseases. Collectively, ROS activated Notch signaling in SK-N-MC cells leading to cell apoptosis.

Authors+Show Affiliations

Institute of Biochemistry and Biophysics, University of Tehran, P.O. Box 13145-1384, Tehran, Iran.No affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

25005833

Citation

Kamarehei, Maryam, and Razieh Yazdanparast. "Modulation of Notch Signaling Pathway to Prevent H2O2/menadione-induced SK-N-MC Cells Death By EUK134." Cellular and Molecular Neurobiology, vol. 34, no. 7, 2014, pp. 1037-45.
Kamarehei M, Yazdanparast R. Modulation of notch signaling pathway to prevent H2O2/menadione-induced SK-N-MC cells death by EUK134. Cell Mol Neurobiol. 2014;34(7):1037-45.
Kamarehei, M., & Yazdanparast, R. (2014). Modulation of notch signaling pathway to prevent H2O2/menadione-induced SK-N-MC cells death by EUK134. Cellular and Molecular Neurobiology, 34(7), 1037-45. https://doi.org/10.1007/s10571-014-0079-0
Kamarehei M, Yazdanparast R. Modulation of Notch Signaling Pathway to Prevent H2O2/menadione-induced SK-N-MC Cells Death By EUK134. Cell Mol Neurobiol. 2014;34(7):1037-45. PubMed PMID: 25005833.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Modulation of notch signaling pathway to prevent H2O2/menadione-induced SK-N-MC cells death by EUK134. AU - Kamarehei,Maryam, AU - Yazdanparast,Razieh, Y1 - 2014/07/09/ PY - 2013/12/18/received PY - 2014/06/24/accepted PY - 2014/7/10/entrez PY - 2014/7/10/pubmed PY - 2015/5/29/medline SP - 1037 EP - 45 JF - Cellular and molecular neurobiology JO - Cell Mol Neurobiol VL - 34 IS - 7 N2 - The brain in Alzheimer's disease is under increased oxidative stress, and this may have a role in the pathogenesis and neural death in this disorder. It has been verified that numerous signaling pathways involved in neurodegenerative disorders are activated in response to reactive oxygen species (ROS). EUK134, a synthetic salen-manganese antioxidant complex, has been found to possess many interesting pharmacological activities awaiting exploration. The present study is to characterize the role of Notch signaling in apoptotic cell death of SK-N-MC cells. The cells were treated with hydrogen peroxide (H2O2) or menadione to induce oxidative stress. The free-radical scavenging capabilities of EUK134 were studied through the MTT assay, glutathione peroxidase (GPx) enzyme activity assay, and glutathione (GSH) Levels. The extents of lipid peroxidation, protein carbonyl formation, and intracellular ROS levels, as markers of oxidative stress, were also studied. Our results showed that H2O2/menadione reduced GSH levels and GPx activity. However, EUK134 protected cells against ROS-induced cell death by down-regulation of lipid peroxidation and protein carbonyl formation as well as restoration of antioxidant enzymes activity. ROS induced apoptosis and increased NICD and HES1 expression. Inhibition of NICD production proved that Notch signaling is involved in apoptosis through p53 activation. Moreover, H2O2/menadione led to Numb protein down-regulation which upon EUK134 pretreatment, its level increased and subsequently prevented Notch pathway activation. We indicated that EUK134 can be a promising candidate in designing natural-based drugs for ROS-induced neurodegenerative diseases. Collectively, ROS activated Notch signaling in SK-N-MC cells leading to cell apoptosis. SN - 1573-6830 UR - https://www.unboundmedicine.com/medline/citation/25005833/Modulation_of_notch_signaling_pathway_to_prevent_H2O2/menadione_induced_SK_N_MC_cells_death_by_EUK134_ L2 - https://doi.org/10.1007/s10571-014-0079-0 DB - PRIME DP - Unbound Medicine ER -