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- Title
Role of the antioxidants on the inactivation of melastatin-like transient receptor potential 2 (TRPM2) cation channel.
- Authors
Naziroğlu, Mustafa; Lückhoff, Andreas
- Abstract
Reactive oxygen species (ROS) including superoxide anion and hydrogen peroxide (H2O2) act as subcellular messengers in such complex processes as mitogenic signal transduction and regulation of cell proliferation when they are generated excessively or when enzymatic and non- enzymatic antioxidant defense systems are impaired. Vitamin E is a lipophilic antioxidant that interferes with the chain reaction of ROS although vitamin C is a hydrophilic molecule that can scavenge several radicals, among them the hydroxyl radical. Melastatin-like transient receptor potential 2 (TRPM2) channel is a redox sensitive Ca2+-permeable cation channel that can be gated by H2O2 binding to the channel's enzymatic Nudix domain. Since the mechanisms that lead to TRPM2 action in response to H2O2 are not understood, we examined the effects of various antioxidants on H2O2- induced TRPM2 cation channel currents in transfected Chinese hamster ovary cells. In our recent studies, we chosen an intracellular Ca concentration calculated to be in the range of 1 µM. H2O2 (10 mM) was added extracellularly to the bath chamber. With these conditions, we were able to evoke TRPM2 currents consistently with H2O2. We next tested whether the vitamins C and E or glutathione (GSH) would prevent or attenuate the induction of TRPM2 currents by H2O2 when applied extracellularly or intracellularly. The H2O2-induced gating of the TRPM2 channel was not prevented or reversed by vitamin E because H2O2 appears to activate TRPM2 by conversion to the hydroxyl radical in the intracellular space after crossing the plasma membrane. The idea was supported by the studies of different authors and they reported that co-treatment with membrane impermeable catalase completely blocked the H2O2- induced Ca + entry and cell death and they also reported that a nonselective radical scavenger, mannitol, prevented cation current by H2O2 in TRPM2-transfected HEK293 cells, suggesting that H2O2 acts by generation of free radicals in cell interior. In conclusion, TRPM2 channels were constitutively activated by H2O2 although we could not detect any inhibitory effect of the antioxidants on H2O2-induced TRPM2 cation channel currents in CHO cells.
- Publication
Cell Membranes & Free Radical Research, 2008, Vol 1, Issue 1, p13
- ISSN
1308-416X
- Publication type
Article