Poly ADP-ribose polymerase-1 and health

Abstract

Niacin (vitamin B3) is required to form nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), which are involved in scores of anabolic and catabolic redox reactions throughout metabolism. It is now understood that NAD+ is also a substrate for several families of ADP-ribosylation reactions, which control processes like DNA repair, replication and transcription, the activity of G-proteins, chromatin structure and intracellular calcium signalling. Poly(ADP-ribose)polymerase-1 (PARP-1) is the most active of the PARP enzymes, and it has been implicated in both prevention and aggravation of disease processes. Inhibition of poly-ADP-ribose formation will tend to cause genomic instability and tumorigenesis in chronic models of DNA damage, but the same inhibition can prevent many acute disease processes, such as stroke, myocardial infarction and septic shock. In models of acute stress, PARP-1 inhibition may protect cellular NAD pools and prevent nuclear factor- κB-dependent inflammatory signalling, while long-term protective roles for PARP-1 include DNA repair and regulation of chromatin structure. Promising new PARP-1 inhibitors may display interactions with dietary niacin status and may have long-term deleterious effects on genomic stability, but may be extremely valuable for the treatment of acute inflammatory conditions.