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Duloxetine Reduces Oxidative Stress, Apoptosis, and Ca2+ Entry Through Modulation of TRPM2 and TRPV1 Channels in the Hippocampus and Dorsal Root Ganglion of Rats.
Mol Neurobiol. 2017 08; 54(6):4683-4695.MN

Abstract

Overload of Ca2+ entry and excessive oxidative stress in neurons are the two main causes of depression. Activation of transient receptor potential (TRP) vanilloid type 1 (TRPV1) and TRP melastatin 2 (TRPM2) during oxidative stress has been linked to neuronal survival. Duloxetine (DULOX) in neurons reduced the effects of Ca2+ entry and reactive oxygen species (ROS) through glutamate receptors, and this reduction of effects may also occur through TRPM2 and TRPV1 channels. In order to better characterize the actions of DULOX in peripheral pain and hippocampal oxidative injury through modulation of TRPM2 and TRPV1, we tested the effects of DULOX on apoptosis and oxidative stress in the hippocampal and dorsal root ganglion (DRG) neurons of rats. Freshly isolated hippocampal and DRG neurons were incubated for 24 h with DULOX. In whole-cell patch-clamp and intracellular-free calcium ([Ca2+]) concentration (Fura-2) experiments, cumene hydroperoxide and ADP-ribose-induced TRPM2 currents in the neurons were inhibited by N-(p-amylcinnamoyl) anthranilic acid (ACA) and capsaicin-induced TRPV1 currents were inhibited by capsazepine (CPZ) incubations. TRPM2 and TRPV1 channel current densities, [Ca2+] concentration, apoptosis, caspase 3, caspase 9, mitochondrial depolarization, and intracellular ROS production values in the neurons were lower in the DULOX group than in controls. In addition, the above values were further decreased by DULOX + CPZ and DULOX + ACA treatments. In conclusion, TRPM2 and TRPV1 channels are involved in Ca2+ entry-induced neuronal death and modulation of the activity of these channels by DULOX treatment may account for their neuroprotective activity against apoptosis, excessive ROS production, and Ca2+ entry.

Authors+Show Affiliations

Department of Psychiatry, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey.Department of Neuroscience, Health Science Institute, Suleyman Demirel University, Isparta, Turkey. mustafanaziroglu@sdu.edu.tr. Neuroscience Research Center, Suleyman Demirel University, 32260, Isparta, Turkey. mustafanaziroglu@sdu.edu.tr.Department of Neuroscience, Health Science Institute, Suleyman Demirel University, Isparta, Turkey.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27443158

Citation

Demirdaş, Arif, et al. "Duloxetine Reduces Oxidative Stress, Apoptosis, and Ca2+ Entry Through Modulation of TRPM2 and TRPV1 Channels in the Hippocampus and Dorsal Root Ganglion of Rats." Molecular Neurobiology, vol. 54, no. 6, 2017, pp. 4683-4695.
Demirdaş A, Nazıroğlu M, Övey İS. Duloxetine Reduces Oxidative Stress, Apoptosis, and Ca2+ Entry Through Modulation of TRPM2 and TRPV1 Channels in the Hippocampus and Dorsal Root Ganglion of Rats. Mol Neurobiol. 2017;54(6):4683-4695.
Demirdaş, A., Nazıroğlu, M., & Övey, İ. S. (2017). Duloxetine Reduces Oxidative Stress, Apoptosis, and Ca2+ Entry Through Modulation of TRPM2 and TRPV1 Channels in the Hippocampus and Dorsal Root Ganglion of Rats. Molecular Neurobiology, 54(6), 4683-4695. https://doi.org/10.1007/s12035-016-9992-1
Demirdaş A, Nazıroğlu M, Övey İS. Duloxetine Reduces Oxidative Stress, Apoptosis, and Ca2+ Entry Through Modulation of TRPM2 and TRPV1 Channels in the Hippocampus and Dorsal Root Ganglion of Rats. Mol Neurobiol. 2017;54(6):4683-4695. PubMed PMID: 27443158.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Duloxetine Reduces Oxidative Stress, Apoptosis, and Ca2+ Entry Through Modulation of TRPM2 and TRPV1 Channels in the Hippocampus and Dorsal Root Ganglion of Rats. AU - Demirdaş,Arif, AU - Nazıroğlu,Mustafa, AU - Övey,İshak Suat, Y1 - 2016/07/21/ PY - 2016/03/05/received PY - 2016/06/14/accepted PY - 2016/7/23/pubmed PY - 2018/4/10/medline PY - 2016/7/23/entrez KW - Apoptosis KW - Duloxetine KW - Oxidative stress KW - Pain KW - TRPV1 SP - 4683 EP - 4695 JF - Molecular neurobiology JO - Mol Neurobiol VL - 54 IS - 6 N2 - Overload of Ca2+ entry and excessive oxidative stress in neurons are the two main causes of depression. Activation of transient receptor potential (TRP) vanilloid type 1 (TRPV1) and TRP melastatin 2 (TRPM2) during oxidative stress has been linked to neuronal survival. Duloxetine (DULOX) in neurons reduced the effects of Ca2+ entry and reactive oxygen species (ROS) through glutamate receptors, and this reduction of effects may also occur through TRPM2 and TRPV1 channels. In order to better characterize the actions of DULOX in peripheral pain and hippocampal oxidative injury through modulation of TRPM2 and TRPV1, we tested the effects of DULOX on apoptosis and oxidative stress in the hippocampal and dorsal root ganglion (DRG) neurons of rats. Freshly isolated hippocampal and DRG neurons were incubated for 24 h with DULOX. In whole-cell patch-clamp and intracellular-free calcium ([Ca2+]) concentration (Fura-2) experiments, cumene hydroperoxide and ADP-ribose-induced TRPM2 currents in the neurons were inhibited by N-(p-amylcinnamoyl) anthranilic acid (ACA) and capsaicin-induced TRPV1 currents were inhibited by capsazepine (CPZ) incubations. TRPM2 and TRPV1 channel current densities, [Ca2+] concentration, apoptosis, caspase 3, caspase 9, mitochondrial depolarization, and intracellular ROS production values in the neurons were lower in the DULOX group than in controls. In addition, the above values were further decreased by DULOX + CPZ and DULOX + ACA treatments. In conclusion, TRPM2 and TRPV1 channels are involved in Ca2+ entry-induced neuronal death and modulation of the activity of these channels by DULOX treatment may account for their neuroprotective activity against apoptosis, excessive ROS production, and Ca2+ entry. SN - 1559-1182 UR - https://www.unboundmedicine.com/medline/citation/27443158/Duloxetine_Reduces_Oxidative_Stress_Apoptosis_and_Ca2+_Entry_Through_Modulation_of_TRPM2_and_TRPV1_Channels_in_the_Hippocampus_and_Dorsal_Root_Ganglion_of_Rats_ L2 - https://dx.doi.org/10.1007/s12035-016-9992-1 DB - PRIME DP - Unbound Medicine ER -