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Homocysteine and cytosolic GSH depletion induce apoptosis and oxidative toxicity through cytosolic calcium overload in the hippocampus of aged mice: involvement of TRPM2 and TRPV1 channels.
Neuroscience. 2015 Jan 22; 284:225-233.N

Abstract

Oxidative stress and apoptosis were induced in neuronal cultures by inhibition of glutathione (GSH) biosynthesis with d,l-buthionine-S,R-sulfoximine (BSO). Transient receptor potential melastatin 2 (TRPM2) and transient receptor potential vanilloid 1 (TRPV1) cation channels are gated by oxidative stress. The oxidant effects of homocysteine (Hcy) may induce activation of TRPV1 and TRPM2 channels in aged mice as a model of Alzheimer's disease (AD). We tested the effects of Hcy, BSO and GSH on oxidative stress, apoptosis and Ca2+ and influx via TRPM2 and TRPV1 channels in the hippocampus of mice. Native mice hippocampal neurons were divided into five groups as follows; control, Hcy, BSO, Hcy+BSO and Hcy+BSO+GSH groups. The neurons in TRPM2 and TRPV1 experiments were stimulated by hydrogen peroxide and capsaicin, respectively. BSO and Hcy incubations increased intracellular free Ca2+ concentrations, reactive oxygen species, apoptosis, mitochondrial depolarization, and levels of caspase 3 and 9. All of these increases were reduced by GSH treatments. Treatment with 2-aminoethoxydiphenyl borate (2-APB) and N-(p-amylcinnamoyl)anthranilic acid (ACA) as potent inhibitors of TRPM2, capsazepine as a potent inhibitor of TRPV1, verapamil+diltiazem (V+D) as inhibitors of the voltage-gated Ca2+ channels (VGCC) and MK-801 as a N-methyl-d-aspartate (NMDA) channel antagonist indicated that GSH depletion and Hcy elevation activated Ca2+ entry into the neurons through TRPM2, TRPV1, VGCC and NMDA channels. Inhibitor roles of 2-APB and capsazepine on the Ca2+ entry higher than in V+D and MK-801 antagonists. In conclusion, these findings support the idea that GSH depletion and Hcy elevation can have damaging effects on hippocampal neurons by perturbing calcium homeostasis, mainly through TRPM2 and TRPV1 channels. GSH treatment can partially reverse these effects.

Authors+Show Affiliations

Department of Biophysics, Faculty of Medicine, University of Suleyman Demirel, Isparta, Turkey.Department of Biophysics, Faculty of Medicine, University of Suleyman Demirel, Isparta, Turkey; Neuroscience Research Center, University of Suleyman Demirel, Isparta, Turkey. Electronic address: mustafanaziroglu@sdu.edu.tr.

Pub Type(s)

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

Language

eng

PubMed ID

25305668

Citation

Övey, İ S., and M Naziroğlu. "Homocysteine and Cytosolic GSH Depletion Induce Apoptosis and Oxidative Toxicity Through Cytosolic Calcium Overload in the Hippocampus of Aged Mice: Involvement of TRPM2 and TRPV1 Channels." Neuroscience, vol. 284, 2015, pp. 225-233.
Övey İS, Naziroğlu M. Homocysteine and cytosolic GSH depletion induce apoptosis and oxidative toxicity through cytosolic calcium overload in the hippocampus of aged mice: involvement of TRPM2 and TRPV1 channels. Neuroscience. 2015;284:225-233.
Övey, İ. S., & Naziroğlu, M. (2015). Homocysteine and cytosolic GSH depletion induce apoptosis and oxidative toxicity through cytosolic calcium overload in the hippocampus of aged mice: involvement of TRPM2 and TRPV1 channels. Neuroscience, 284, 225-233. https://doi.org/10.1016/j.neuroscience.2014.09.078
Övey İS, Naziroğlu M. Homocysteine and Cytosolic GSH Depletion Induce Apoptosis and Oxidative Toxicity Through Cytosolic Calcium Overload in the Hippocampus of Aged Mice: Involvement of TRPM2 and TRPV1 Channels. Neuroscience. 2015 Jan 22;284:225-233. PubMed PMID: 25305668.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Homocysteine and cytosolic GSH depletion induce apoptosis and oxidative toxicity through cytosolic calcium overload in the hippocampus of aged mice: involvement of TRPM2 and TRPV1 channels. AU - Övey,İ S, AU - Naziroğlu,M, Y1 - 2014/10/08/ PY - 2014/08/12/received PY - 2014/09/29/revised PY - 2014/09/30/accepted PY - 2014/10/12/entrez PY - 2014/10/12/pubmed PY - 2015/12/23/medline KW - TRPM2 and TRPV1 channels KW - apoptosis KW - hippocampus KW - homocysteine KW - oxidative stress SP - 225 EP - 233 JF - Neuroscience JO - Neuroscience VL - 284 N2 - Oxidative stress and apoptosis were induced in neuronal cultures by inhibition of glutathione (GSH) biosynthesis with d,l-buthionine-S,R-sulfoximine (BSO). Transient receptor potential melastatin 2 (TRPM2) and transient receptor potential vanilloid 1 (TRPV1) cation channels are gated by oxidative stress. The oxidant effects of homocysteine (Hcy) may induce activation of TRPV1 and TRPM2 channels in aged mice as a model of Alzheimer's disease (AD). We tested the effects of Hcy, BSO and GSH on oxidative stress, apoptosis and Ca2+ and influx via TRPM2 and TRPV1 channels in the hippocampus of mice. Native mice hippocampal neurons were divided into five groups as follows; control, Hcy, BSO, Hcy+BSO and Hcy+BSO+GSH groups. The neurons in TRPM2 and TRPV1 experiments were stimulated by hydrogen peroxide and capsaicin, respectively. BSO and Hcy incubations increased intracellular free Ca2+ concentrations, reactive oxygen species, apoptosis, mitochondrial depolarization, and levels of caspase 3 and 9. All of these increases were reduced by GSH treatments. Treatment with 2-aminoethoxydiphenyl borate (2-APB) and N-(p-amylcinnamoyl)anthranilic acid (ACA) as potent inhibitors of TRPM2, capsazepine as a potent inhibitor of TRPV1, verapamil+diltiazem (V+D) as inhibitors of the voltage-gated Ca2+ channels (VGCC) and MK-801 as a N-methyl-d-aspartate (NMDA) channel antagonist indicated that GSH depletion and Hcy elevation activated Ca2+ entry into the neurons through TRPM2, TRPV1, VGCC and NMDA channels. Inhibitor roles of 2-APB and capsazepine on the Ca2+ entry higher than in V+D and MK-801 antagonists. In conclusion, these findings support the idea that GSH depletion and Hcy elevation can have damaging effects on hippocampal neurons by perturbing calcium homeostasis, mainly through TRPM2 and TRPV1 channels. GSH treatment can partially reverse these effects. SN - 1873-7544 UR - https://www.unboundmedicine.com/medline/citation/25305668/Homocysteine_and_cytosolic_GSH_depletion_induce_apoptosis_and_oxidative_toxicity_through_cytosolic_calcium_overload_in_the_hippocampus_of_aged_mice:_involvement_of_TRPM2_and_TRPV1_channels_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(14)00848-3 DB - PRIME DP - Unbound Medicine ER -