New molecular mechanisms on the activation of TRPM2 channels by oxidative stress and ADP-ribose

Abstract

The Na + and Ca 2+ -permeable melastatin related transient receptor potential (TRPM2) cation channels can be gated either by ADP-ribose (ADPR) in concert with Ca 2+ or by hydrogen peroxide (H 2 O 2 ), an experimental model for oxidative stress, and binding to the channel's enzymatic Nudix domain. Since the mechanisms that lead to TRPM2 inhibiting in response to ADPR and H 2 O 2 are not understood, I reviewed the effects of various inhibitors such as flufenamic acid and PARP inhibitors on ADPR, NAD + and H 2 O 2 -induced TRPM2 currents. In our experimental study, TRPM2 cation channels in chinese hamster ovary transected cells were gated both by ADPR and NAD + . In addition, H 2 O 2 seems to activate TRPM2 by changing to the hydroxyl radical in the intracellular space after passing the plasma membrane. Experimental studies with respect to patch-clamp and Ca 2+ imaging, inhibitor roles of antioxidants are also summarized in the review. © 2007 Springer Science+Business Media, LLC.