The interleukin 1β‐converting enzyme inhibitor CrmA prevents Apo1/Fas‐ but not glucocorticoid‐induced poly(ADP‐ribose) polymerase cleavage and apoptosis in lymphoblastic leukemia cells

FEBS Letters

Villunger, Andreas¹  Greil, Richard¹  Auer, Bernhard²  Geley, Stephan³  Egle, Alexander¹  Heidacher, Daniela²  Hartmann, Bernd L³  Kapelari, Klaus³  Kofler, Reinhard³ 

[1] University Hospital for Internal Medicine, Division of Hematology, University of Innbruck, Innsbruck, Austria;Institute of Biochemistry, University of Innbruck, Innsbruck, Austria;Institute for General and Experimental Pathology, Division of Molecular Pathophysiology, Fritz-Pregl-Str. 3, University of Innbruck, A-6020 Innsbruck, Austria

关键词: Apoptosis;    Glucocorticoid;    Protease;    ICE;    Apo1/Fas;    Human;    Leukemia;    T-cell;    Poly(ADP-ribose) polymerase;    FACS;    fluorescence-activated cell sorter;    GC;    glucocorticoid(s);    ICE;    interleukin 1β-converting enzyme;    PARP;    poly(ADP-ribose) polymerase;   

DOI  :  10.1016/S0014-5793(96)01496-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Glucocorticoids (GC) induce programmed cell death (apoptosis) in immature lymphocytes and are an essential component in the therapy of acute lymphatic leukemia. The mechanism underlying GC-induced apoptosis particularly in leukemia cells is, however, not well understood. Most forms of apoptosis seem to employ a common final effector pathway characterized by specific proteolytic events mediated by interleukin 1β-converting enzyme (ICE) and/or other ICE-like cysteine proteases. These events may result in the morphologic changes characteristic of apoptosis. To determine whether a similar proteolytic pathway is activated during GC-induced leukemia cell apoptosis, we investigated poly(ADP-ribose) polymerase (PARP), a typical target of ICE-like proteases, during GC-induced apoptosis of the human acute T-cell leukemic cell line CEM-C7H2. Our studies showed proteolytic PARP cleavage suggestive of activation of ICE-like proteases that preceeded morphologic signs of apoptosis. We further established stably transfected CEM-C7H2 sublines expressing the cowpox virus protein CrmA that inhibits some, but not all, ICE-like proteases. GC-induced PARP cleavage and apoptosis were neither inhibited nor delayed in crmA-expressing cell lines. In contrast, crmA expression rendered the same lines resistant to Apo1/Fas-induced PARP cleavage and apoptosis. Thus, different proteases might be activated during the effector phases of GC- and Apo1/Fas-induced apoptosis in human leukemia cells.

【 授权许可】

Unknown