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Glutathione modulates Ca(2+) influx and oxidative toxicity through TRPM2 channel in rat dorsal root ganglion neurons.
J Membr Biol. 2011 Aug; 242(3):109-18.JM

Abstract

Glutathione (GSH) is the most abundant thiol antioxidant in mammalian cells and maintains thiol redox in the cells. GSH depletion has been implicated in the neurobiology of sensory neurons. Because the mechanisms that lead to melastatin-like transient receptor potential 2 (TRPM2) channel activation/inhibition in response to glutathione depletion and 2-aminoethyldiphenyl borinate (2-APB) administration are not understood, we tested the effects of 2-APB and GSH on oxidative stress and buthionine sulfoximine (BSO)-induced TRPM2 cation channel currents in dorsal root ganglion (DRG) neurons of rats. DRG neurons were freshly isolated from rats and the neurons were incubated for 24 h with BSO. In whole-cell patch clamp experiments, TRPM2 currents in the rat were consistently induced by H(2)O(2) or BSO. TRPM2 channels current densities and cytosolic free Ca(2+) content of the neurons were higher in BSO and H(2)O(2) groups than in control. However, the current densities and cytosolic Ca(2+) release were also higher in the BSO + H(2)O(2) group than in the H(2)O(2) alone. When intracellular GSH is introduced by pipette TRPM2 channel currents were not activated by BSO, H(2)O(2) or rotenone. BSO and H(2)O(2)-induced Ca(2+) gates were blocked by the 2-APB. Glutathione peroxidase activity, lipid peroxidation and GSH levels in the DRG neurons were also modulated by GSH and 2-APB inhibition. In conclusion, we observed the protective role of 2-APB and GSH on Ca(2+) influx through a TRPM2 channel in intracellular GSH depleted DRG neurons. Since cytosolic glutathione depletion is a common feature of neuropathic pain and diseases of sensory neuron, our findings are relevant to the etiology of neuropathology in DRG neurons.

Authors+Show Affiliations

Department of Biophysics, Faculty of Medicine, University of Süleyman Demirel, 32260 Isparta, Turkey. mnaziroglu@med.sdu.edu.trNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

21748272

Citation

Nazıroğlu, Mustafa, et al. "Glutathione Modulates Ca(2+) Influx and Oxidative Toxicity Through TRPM2 Channel in Rat Dorsal Root Ganglion Neurons." The Journal of Membrane Biology, vol. 242, no. 3, 2011, pp. 109-18.
Nazıroğlu M, Özgül C, Çiğ B, et al. Glutathione modulates Ca(2+) influx and oxidative toxicity through TRPM2 channel in rat dorsal root ganglion neurons. J Membr Biol. 2011;242(3):109-18.
Nazıroğlu, M., Özgül, C., Çiğ, B., Doğan, S., & Uğuz, A. C. (2011). Glutathione modulates Ca(2+) influx and oxidative toxicity through TRPM2 channel in rat dorsal root ganglion neurons. The Journal of Membrane Biology, 242(3), 109-18. https://doi.org/10.1007/s00232-011-9382-6
Nazıroğlu M, et al. Glutathione Modulates Ca(2+) Influx and Oxidative Toxicity Through TRPM2 Channel in Rat Dorsal Root Ganglion Neurons. J Membr Biol. 2011;242(3):109-18. PubMed PMID: 21748272.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Glutathione modulates Ca(2+) influx and oxidative toxicity through TRPM2 channel in rat dorsal root ganglion neurons. AU - Nazıroğlu,Mustafa, AU - Özgül,Cemil, AU - Çiğ,Bilal, AU - Doğan,Salih, AU - Uğuz,Abdulhadi Cihangir, Y1 - 2011/07/12/ PY - 2011/05/21/received PY - 2011/06/17/accepted PY - 2011/7/13/entrez PY - 2011/7/13/pubmed PY - 2011/12/13/medline SP - 109 EP - 18 JF - The Journal of membrane biology JO - J Membr Biol VL - 242 IS - 3 N2 - Glutathione (GSH) is the most abundant thiol antioxidant in mammalian cells and maintains thiol redox in the cells. GSH depletion has been implicated in the neurobiology of sensory neurons. Because the mechanisms that lead to melastatin-like transient receptor potential 2 (TRPM2) channel activation/inhibition in response to glutathione depletion and 2-aminoethyldiphenyl borinate (2-APB) administration are not understood, we tested the effects of 2-APB and GSH on oxidative stress and buthionine sulfoximine (BSO)-induced TRPM2 cation channel currents in dorsal root ganglion (DRG) neurons of rats. DRG neurons were freshly isolated from rats and the neurons were incubated for 24 h with BSO. In whole-cell patch clamp experiments, TRPM2 currents in the rat were consistently induced by H(2)O(2) or BSO. TRPM2 channels current densities and cytosolic free Ca(2+) content of the neurons were higher in BSO and H(2)O(2) groups than in control. However, the current densities and cytosolic Ca(2+) release were also higher in the BSO + H(2)O(2) group than in the H(2)O(2) alone. When intracellular GSH is introduced by pipette TRPM2 channel currents were not activated by BSO, H(2)O(2) or rotenone. BSO and H(2)O(2)-induced Ca(2+) gates were blocked by the 2-APB. Glutathione peroxidase activity, lipid peroxidation and GSH levels in the DRG neurons were also modulated by GSH and 2-APB inhibition. In conclusion, we observed the protective role of 2-APB and GSH on Ca(2+) influx through a TRPM2 channel in intracellular GSH depleted DRG neurons. Since cytosolic glutathione depletion is a common feature of neuropathic pain and diseases of sensory neuron, our findings are relevant to the etiology of neuropathology in DRG neurons. SN - 1432-1424 UR - https://www.unboundmedicine.com/medline/citation/21748272/Glutathione_modulates_Ca_2+__influx_and_oxidative_toxicity_through_TRPM2_channel_in_rat_dorsal_root_ganglion_neurons_ L2 - https://dx.doi.org/10.1007/s00232-011-9382-6 DB - PRIME DP - Unbound Medicine ER -