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TRPM2 channel protective properties of N-acetylcysteine on cytosolic glutathione depletion dependent oxidative stress and Ca2+ influx in rat dorsal root ganglion.
Physiol Behav. 2012 May 15; 106(2):122-8.PB

Abstract

N-acetylcysteine (NAC) is a thiol-containing (sulphydryl donor) antioxidant, which contributes to regeneration of glutathione (GSH) and also acts through a direct reaction with free radicals. Thiol depletion has been implicated in the neurobiology of sensory neurons and pain. We reported recently an activator role of intracellular GSH depletion on calcium influx through transient receptor potential melastatin-like 2 (TRPM2) channels in rat dorsal root ganglion (DRG). NAC may have a protective role on calcium influx through regulation of TRPM2 channels in the neurons. Therefore, we tested the effects of NAC on TRPM2 channel currents in cytosolic GSH depleted DRG in rats. DRG neurons were freshly isolated from rats and the neurons were incubated for 24 h with buthionine sulfoximine (BSO). In whole-cell patch clamp experiments, TRPM2 currents in the DRG incubated with BSO were gated by H(2)O(2). TRPM2 channels current densities, cytosolic free Ca(2+) content, and lipid peroxidation values in the neurons were higher in H(2)O(2) and BSO + H(2)O(2) group than in controls; however GSH and GSH peroxidase (GSH-Px) values were decreased. BSO + H(2)O(2)-induced TRPM2 channel gating was totally inhibited by extracellular NAC and partially inhibited by 2-aminoethyl diphenylborinate. GSH-Px activity, lipid peroxidation and GSH levels in the DRG neurons were also modulated by NAC. In conclusion, we observed a modulator role of NAC on Ca(2+) influx through a TRPM2 channel in intracellular GSH depleted DRG neurons. NAC incubation before BSO exposure appears to be more protective than NAC incubation after BSO exposure. Since cytosolic thiol group depletion is a common feature of neuropathic pain, our findings are relevant to the etiology and treatment of pain neuropathology in DRG neurons.

Authors+Show Affiliations

Department of Biophysics, Faculty of Medicine, University of Suleyman Demirel, Isparta, Turkey. cmlozgl@gmail.comNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

22300897

Citation

Özgül, C, and M Nazıroğlu. "TRPM2 Channel Protective Properties of N-acetylcysteine On Cytosolic Glutathione Depletion Dependent Oxidative Stress and Ca2+ Influx in Rat Dorsal Root Ganglion." Physiology & Behavior, vol. 106, no. 2, 2012, pp. 122-8.
Özgül C, Nazıroğlu M. TRPM2 channel protective properties of N-acetylcysteine on cytosolic glutathione depletion dependent oxidative stress and Ca2+ influx in rat dorsal root ganglion. Physiol Behav. 2012;106(2):122-8.
Özgül, C., & Nazıroğlu, M. (2012). TRPM2 channel protective properties of N-acetylcysteine on cytosolic glutathione depletion dependent oxidative stress and Ca2+ influx in rat dorsal root ganglion. Physiology & Behavior, 106(2), 122-8. https://doi.org/10.1016/j.physbeh.2012.01.014
Özgül C, Nazıroğlu M. TRPM2 Channel Protective Properties of N-acetylcysteine On Cytosolic Glutathione Depletion Dependent Oxidative Stress and Ca2+ Influx in Rat Dorsal Root Ganglion. Physiol Behav. 2012 May 15;106(2):122-8. PubMed PMID: 22300897.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - TRPM2 channel protective properties of N-acetylcysteine on cytosolic glutathione depletion dependent oxidative stress and Ca2+ influx in rat dorsal root ganglion. AU - Özgül,C, AU - Nazıroğlu,M, Y1 - 2012/01/24/ PY - 2011/12/16/received PY - 2012/01/11/revised PY - 2012/01/17/accepted PY - 2012/2/4/entrez PY - 2012/2/4/pubmed PY - 2012/7/28/medline SP - 122 EP - 8 JF - Physiology & behavior JO - Physiol Behav VL - 106 IS - 2 N2 - N-acetylcysteine (NAC) is a thiol-containing (sulphydryl donor) antioxidant, which contributes to regeneration of glutathione (GSH) and also acts through a direct reaction with free radicals. Thiol depletion has been implicated in the neurobiology of sensory neurons and pain. We reported recently an activator role of intracellular GSH depletion on calcium influx through transient receptor potential melastatin-like 2 (TRPM2) channels in rat dorsal root ganglion (DRG). NAC may have a protective role on calcium influx through regulation of TRPM2 channels in the neurons. Therefore, we tested the effects of NAC on TRPM2 channel currents in cytosolic GSH depleted DRG in rats. DRG neurons were freshly isolated from rats and the neurons were incubated for 24 h with buthionine sulfoximine (BSO). In whole-cell patch clamp experiments, TRPM2 currents in the DRG incubated with BSO were gated by H(2)O(2). TRPM2 channels current densities, cytosolic free Ca(2+) content, and lipid peroxidation values in the neurons were higher in H(2)O(2) and BSO + H(2)O(2) group than in controls; however GSH and GSH peroxidase (GSH-Px) values were decreased. BSO + H(2)O(2)-induced TRPM2 channel gating was totally inhibited by extracellular NAC and partially inhibited by 2-aminoethyl diphenylborinate. GSH-Px activity, lipid peroxidation and GSH levels in the DRG neurons were also modulated by NAC. In conclusion, we observed a modulator role of NAC on Ca(2+) influx through a TRPM2 channel in intracellular GSH depleted DRG neurons. NAC incubation before BSO exposure appears to be more protective than NAC incubation after BSO exposure. Since cytosolic thiol group depletion is a common feature of neuropathic pain, our findings are relevant to the etiology and treatment of pain neuropathology in DRG neurons. SN - 1873-507X UR - https://www.unboundmedicine.com/medline/citation/22300897/TRPM2_channel_protective_properties_of_N_acetylcysteine_on_cytosolic_glutathione_depletion_dependent_oxidative_stress_and_Ca2+_influx_in_rat_dorsal_root_ganglion_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0031-9384(12)00034-0 DB - PRIME DP - Unbound Medicine ER -