A role for the subcellular localization of Bax in differentiation-induced resistance to apoptosis in HL-60 cells.
The promyelocytic leukemia cell line HL-60 was induced to undergo granulocytic differentiation by treatment with dimethyl sulphoxide (DMSO). The differentiated HL-60 cells were resistant to apoptosis induction by etoposide treatment. The resistant cells did not show evidence of cytochrome c release from the mitochondria or cleavage of caspase-3. Because of the important role of Bax in the regulation of apoptosis in HL-60 cells and neutrophils, we studied its levels and sub-cellular localization in susceptible and resistant HL-60 cells. Although, there was no significant change in Bax levels as a result of DMSO treatment, resistance to apoptosis was associated with lack of Bax translocation from the cytosol to the mitochondria-containing fraction. These results emphasize the role of Bax in apoptosis and point out the importance of studying not only its level, but also its sub-cellular localization.
Abdelhaleem
Mohamed
M
Department of Paediatric Laboratory Medicine, Hospital for Sick Children and The University of Toronto, ON, Canada. mohamed.abdelhaleem@sickkids.ca
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D003574:Cytochrome c Group / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000494:pharmacology; D018922:HL-60 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2; D013347:Subcellular Fractions / Q000378:metabolism; D051028:bcl-2-Associated X Protein
D000972:Antineoplastic Agents, Phytogenic; C494826:BAX protein, human; D003574:Cytochrome c Group; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D005047:Etoposide; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D004121:Dimethyl Sulfoxide