Premium
Bcl‐2 phosphorylation is required for inhibition of oxidative stress‐induced lysosomal leak and ensuing apoptosis
Author(s) -
Zhao Ming,
Eaton John W.,
Brunk Ulf T.
Publication year - 2001
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(01)03185-4
Subject(s) - oxidative stress , microbiology and biotechnology , phosphorylation , apoptosis , oxidative phosphorylation , chemistry , leak , biochemistry , biology , engineering , environmental engineering
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, C 2 ‐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.