Delayed oxidant‐induced cell death involves activation of phospholipase A2

FEBS Letters

Zhao, Ming¹  Brunk, Ulf T.¹  Eaton, John W.¹ 

[1] Division of Pathology II, Faculty of Health Sciences, Linköping University, SE-581 85 Linköping, Sweden

关键词: Apoptosis;    B-Cell leukemia/lymphoma 2;    Lysosome stability;    Oxidative stress;    Phospholipase A2;    AA;    arachidonic acid;    AO;    acridine orange;    Bcl-2;    B-cell leukemia/lymphoma 2;    BPB;    4-bromophenacyl bromide;    DOTAP;    N-[1-(2;    3-dioleoyl)propyl]-N;    N;    N-trimethyl-ammonium salt;    PLA2;    phospholipase A2;   

DOI  :  10.1016/S0014-5793(01)03184-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Short-term (1 h) exposure of cells to a low steady-state concentration of H₂O₂ causes no immediate cell death but apoptosis occurs several hours later. This delayed cell death may arise from activation of phospholipases, in particular phospholipase A2 (PLA2), which may destabilize lysosomal and mitochondrial membranes. Indeed, the secretory PLA2 (sPLA2) inhibitor 4-bromophenacyl bromide diminishes both delayed lysosomal rupture and apoptosis. Furthermore, sPLA2 activation by mellitin, or direct micro-injection of sPLA2, causes lysosomal rupture and apoptosis. Finally, B-cell leukemia/lymphoma 2 (Bcl-2) over-expression prevents oxidant-induced activation of PLA2, delayed lysosomal destabilization and apoptosis. This supports a causal association between PLA2 activation and delayed oxidant-induced cell death and suggests that Bcl-2 may suppress apoptosis by preventing PLA2 activation.

【 授权许可】

Unknown