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

FEBS Letters

Meβmer, Udo K.¹  Reimer, Dietrich M.¹  Reed, John C.²  Brüne, Bernhard¹ 

[1] University of Erlangen-Nürnberg, Faculty of Medicine, Department of Medicine IV-Experimental Division, Loschgestraβe 8, 91054 Erlangen, Germany;La Jolla Cancer Research Foundation, Cancer Research Center, La Jolla, CA, USA

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;   

DOI  :  10.1016/0014-5793(96)00311-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 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.

【 授权许可】

Unknown