Vitamin E modulates oxidative stress and protein kinase C activator (PMA)-induced TRPM2 channel gate in dorsal root ganglion of rats.
It is well known that Ca(2+) influx through cation channels induces peripheral pain in dorsal root ganglion (DRG) neurons. Melastatin-like transient receptor potential 2 (TRPM2) channel is a oxidative redox sensitive Ca(2+)-permeable cation channel. There is scarce report on block of the channels. Since the mechanisms that lead to TRPM2 inhibition in response to oxidative stress and protein kinase C (PKC) activation are not understood, we investigated effects of the antioxidants on the inhibition of TRPM2 channel currents in the DRG neurons of rats. The DRG peripheral neurons were freshly isolated from rats and the neurons were incubated by phorbol 12-myristate 13-acetate (PMA) which leads to activation of PKC and cause oxidative stress. In whole-cell patch clamp experiments, TRPM2 currents in the DRG incubated with PMA were stimulated by H2O2. In addition, the PMA-induced activation of TRPM2 channels were blocked by nonspecific TRPM2 channels inhibitors [2-aminoethyl diphenylborinate (2-APB) and N-(p-amylcinnamoyl)anthranilic acid (ACA)]. The currents in the neurons are also totally blocked by vitamin E incubation. However, administration of catalase and vitamin C with/without the vitamin E incubation did not block the currents. In conclusion, we indicated that vitamin E modulated oxidative stress-induced TRPM2 channel activation in the DRG neurons. The results may be useful modulation of oxidative stress-induced peripheral pain in sensory neurons.
Neuroscience Research Center, University of Suleyman Demirel, Isparta, Turkey, mustafanaziroglu@sdu.edu.tr.
Mustafa
M
Nazıroğlu
Cemil
C
Özgül
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species; D050053:TRPM Cation Channels / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives* / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology*
D017382:Reactive Oxygen Species; D050053:TRPM Cation Channels; C544443:TRPM2 protein, mouse; C557080:Trpm2 protein, rat; D014810:Vitamin E; C016658:phorbolol myristate acetate; D006861:Hydrogen Peroxide; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium