PARP-1 regulates pro-inflammatory cell death (34.13)

Abstract

Abstract PARP-1(poly (ADP-ribose) polymerase 1), an enzyme involved in DNA repair, is a nuclear chromatin associated multifunctional protein and belongs to a large family of enzymes that can synthesize long branched polymers of ADP-ribose units by using NAD+( Nicotinamide adenine dinucleotide) as the substrate. DNA strand nicks and breaks activate PARP-1 and the activated enzyme makes branched chains of up to 200 ADP-ribose units and adds covalently to various nuclear proteins such as histones and especially PARP-1 itself. PARP-1 has been shown to play a major role in a number of pathophysiological situations. In this study, we show that cytokine and chemokine profiles from PARP-WT and -KO BMDM showed no significant differences. However, IL1-β secretion is reduced in PARP-1 deficient macrophages, suggesting a role for PARP-1 in pro-inflammatory signaling. PARP-1 deficient macrophages had displayed prominent protection from pro-inflammatory cell death in response to LPS+ATP stimuli. Together, these results demonstrate that PARP-1 contribute to the pathophysiology by regulating the pro-inflammatory cytokine profiles.