Bcl‐2 phosphorylation is required for inhibition of oxidative stress‐induced lysosomal leak and ensuing apoptosis

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;    Protein kinase C;    AA;    arachidonic acid;    AO;    acridine orange;    Bcl-2;    B-cell leukemia/lymphoma 2;    DOTAP;    N-[1-(2;    3-dioleoyl)propyl]-N;    N;    N-trimethyl-ammonium salt;    OA;    okadaic acid;    LY;    lucifer yellow;    PKC;    protein kinase C;    PLA2;    phospholipase A2;    PMA;    phorbol 12-myristate 13-acetate;    PP2A;    protein phosphatase 2A;   

DOI  :  10.1016/S0014-5793(01)03185-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

B-cell leukemia/lymphoma 2 (Bcl-2) blocks oxidant-induced apoptosis at least partly by stabilizing lysosomes. Here we report that phosphorylation of Bcl-2 may be required for these protective effects. J774 cells overexpressing wild-type Bcl-2 resist oxidant-induced lysosomal leak as well as apoptosis, and this protection is amplified by pretreatment with phorbol 12-myristate 13-acetate (which promotes protein kinase C (PKC)-dependent phosphorylation of Bcl-2). In contrast, cells overexpressing the Bcl-2 mutant S70A (which cannot be phosphorylated) are not protected in either circumstance. Transfection with Bcl-2(S70E), a constitutively active Bcl-2 mutant which does not require phosphorylation, is protective independent of PKC activation. In contrast, C₂-ceramide, a putative protein phosphatase 2A activator, abolishes the protective effects of wild-type Bcl-2 overexpression but does not diminish protection afforded by Bcl-2(S70E). Additional results suggest that, perhaps as a consequence of lysosomal stabilization, Bcl-2 may prevent activation of phospholipase A2, an event potentially important in the ultimate initiation of apoptosis.

【 授权许可】

Unknown