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

[摘要]

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.

[学科分类] 生物化学/生物物理

[关键词] Nitric oxide;Apoptosis;PARP cleavage;DNA fragmentation;p53 accumulation;Bcl-2;GSNO;S-nitrosoglutathione;LPS;lipopolysaccharide;IFN-γ;interferon-γ;Rbcl2–14;Bcl-2 transfected RAW 264.7 macrophages clone 14;PARP;poly(ADP-ribose) polymerase