Inhibition of TRPM2 function by PARP inhibitors protects cells from oxidative stress-induced death.
TRPM2 is a member of the transient receptor potential (TRP) protein superfamily of calcium-permeable, voltage-independent ion channels expressed in nonexcitable cells. Activation of TRPM2 by oxidative stress results in calcium influx and susceptibility to cell death, whereas inhibition of TRPM2 function enhances cell survival. In the present edition of this journal, Fonfria et al. demonstrate a role for poly(ADP ribose) polymerase (PARP) as a mediator between oxidative stress and TRPM2 activation. They present evidence that inhibition of either PARP or TRPM2 protects cells from plasma membrane damage and cell death. The therapeutic implications of this important observation are discussed.
Miller
Barbara A
BA
Henry Hood Research Program, Sigfried and Janet Weis Center for Research, Geisinger Clinic, Danville, PA 17822, USA. bmiller3@psu.edu
D002118:Calcium / Q000502:physiology; D016923:Cell Death / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007473:Ion Channels / Q000037:antagonists & inhibitors*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors*; D009243:NAD / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D015290:Second Messenger Systems / Q000502:physiology; D050053:TRPM Cation Channels
D007473:Ion Channels; D008565:Membrane Proteins; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D050053:TRPM Cation Channels; C121934:TRPM2 protein, human; D009243:NAD; D002118:Calcium