POLY(ADP-RIBOSE) SIGNALISE IN OXIDATIVE STRESS

Abstract

Poly-ADP-ribosylation is an NAD-dependent protein modification reaction. In various oxidative stress-related paradigms DNA breaks activate poly(ADP-ribose) polymerase (PARP) enzymes which in turn modify target proteins with NAD-derived (ADP-ribose)n polymers. This reversible protein modification (PARylation) regulates transcription, kinase cascades, metabolism, differentiation, autophagy, cell death only to name a few cell functions and fates. Moreover, it leads to diverse biological outcomes with wide ranging implications for diseases as diverse as diabetes, inflammation, ischemia-reperfusion injury and cancer. Pathways leading to the formation of advanced glycation endproducts (AGEs) as well as cellular effects of AGEs are accompanied by overproduction of reactive oxygen and nitrogen species and as such may be intertwined with PARylation-related pathologies. The lecture aims to highlight proven and possible interactions between the oxidative stress-induced PARylation events and AGE-related pathologies.