Blenn C Wyrsch P Bader J Bollhalder M Althaus FR 2011 Oxidative DNA damage to cells activates poly(ADP-ribose)polymerase-1 (PARP-1) and the poly(ADP-ribose) formed is rapidly degraded to ADP-ribose by poly(ADP-ribose)glycohydrolase (PARG). Here we show that PARP-1 and PARG control extracellular Ca(2+) fluxes through melastatin-like transient receptor potential 2 channels (TRPM2) in a cell death signaling pathway. TRPM2 activation accounts for essentially the entire Ca(2+) influx into the cytosol, activating caspases and causing the translocation of apoptosis inducing factor (AIF) from the inner mitochondrial membrane to the nucleus followed by cell death. Abrogation of PARP-1 or PARG function disrupts these signals and reduces cell death. ADP-ribose-loading of cells induces Ca(2+) fluxes in the absence of oxidative damage, suggesting that ADP-ribose is the key metabolite of the PARP-1/PARG system regulating TRPM2. We conclude that PARP-1/PARG control a cell death signal pathway that operates between five different cell compartments and communicates via three types of chemical messengers: a nucleotide, a cation, and proteins. application/pdf https://sonar.ch/global/documents/235953 eng info:eu-repo/semantics/altIdentifier/doi/10.1007/s00018-010-0533-1 info:eu-repo/semantics/altIdentifier/pmid/20878536 info:eu-repo/semantics/openAccess Cellular and molecular life sciences : CMLS. - 2011 Animals Calcium Caspases Cell Death Cells, Cultured Fibroblasts Gene Expression Regulation Glycoside Hydrolases Hydrogen Peroxide Mice Oxidants Oxidative Stress Poly(ADP-ribose)glycohydrolase is an upstream regulator of Ca2+ fluxes in oxidative cell death. http://purl.org/coar/resource_type/c_6501