Differential effect of Bcl-xl over-expression on cell death of the monocytic leukemia cell line U937.
We studied the effect of over-expression of Bcl-xl on cell death of the monocytic cell line U937. Over-expression of Bcl-xl inhibits apoptotic changes induced by Etoposide including cytochrome-c release, caspase-3 activation and DNA fragmentation. However, Etoposide treatment resulted in cell death in U937 cells over-expressing Bcl-xl, which had a necrotic-like phenotype with no evidence of caspase-3 activation. On the other hand, Bcl-xl over-expression did not prevent U937 cell apoptotic cell death in response to the specific proteasome inhibitor Lactacystin. There was no significant change in the level of Bcl-xl or evidence of its cleavage. These results suggest that Bcl-xl over-expression does not confer protection against cell death in U937 cells and that Lactacystin utilizes an apoptotic pathway not susceptible to Bcl-xl inhibition.
Abdelhaleem
Mohamed
M
Division of Haematopathology, Department of Paediatric Laboratory Medicine, Hospital for Sick Children, University of Toronto, Toronto, Canada. mohamed.abdelhaleem@sickkids.ca
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology*; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D009336:Necrosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000502:physiology*; D020298:U937 Cells; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; C067713:lactacystin; D005047:Etoposide; D000111:Acetylcysteine