Nitric oxide induced poly(ADP‐ribose) polymerase cleavage in RAW 264.7 macrophage apoptosis is blocked by Bcl‐2

Abstract

Endogenously generated or exogenously supplied nitric oxide causes cleavage of poly(ADP‐ribose) polymerase (PARP) and apoptotic cell death in RAW 264.7 macrophages. With the use of NO donors such as S‐nitrosoglutathione or spermine‐NO we established that PARP digestion occurs in parallel with DNA fragmentation, and is preceded by accumulation of the tumor suppressor gene product p53. PARP cleavage in response to lipopolysaccharide and interferon‐γ treatment is prevented by , thus proving a NO requirement. Endogenous NO generation, p53 accumulation, and PARP degradation occurred prior to the detection of significant chromatin condensation. In contrast, in stable Bcl‐2 transfected cells, NO‐initiated PARP cleavage was almost completely blocked. Our data implicate PARP as a proteolytic substrate during NO‐mediated apoptotic cell death in RAW 264.7 macrophages and establish Bcl‐2 as an efficient signal terminator in this process.