Phosphatidylserine exposure during apoptosis is a cell-type-specific event and does not correlate with plasma membrane phospholipid scramblase expression.
Phosphatidylserine (PS) exposure on the surface of cells has been considered a characteristic feature of apoptosis. However, we demonstrate herein that externalization of PS occurs in a cell-type-specific, albeit caspase-dependent, manner. Moreover, we could find no correlation in six different cell lines between the level of expression of the phospholipid (PL) scramblase and the capacity of these cells to externalize PS during apoptosis. Overexpression of PL scramblase in Raji cells, which exhibit low constitutive expression of this enzyme, by retroviral transduction of PL scramblase or treatment of the cells with interferon-alpha, failed to confer the capacity to expose PS in response to apoptotic stimuli. However, the lack of PS exposure in some cell types was not due to their inability to translocate PS molecules to the cell surface, since incubation with thiol reactive agents, such as N-ethylmaleimide, disulfiram and diamide, yielded rapid and pronounced PS exposure in all cell lines. These data suggest that plasma membrane PS exposure is not an obligatory component of the apoptotic phenotype, and that PL scramblase is not the sole determinant of PS externalization in apoptotic cells when this occurs.
Fadeel
B
B
Division of Toxicology, Karolinska Institutet, Stockholm, 171 77, Sweden.
Gleiss
B
B
Högstrand
K
K
Chandra
J
J
Wiedmer
T
T
Sims
P J
PJ
Henter
J I
JI
Orrenius
S
S
Samali
A
A
D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D053938:DNA Fragmentation / Q000187:drug effects; D004789:Enzyme Activation; D005047:Etoposide / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D010718:Phosphatidylserines / Q000378:metabolism*; D049294:Phospholipid Transfer Proteins; D013439:Sulfhydryl Reagents / Q000494:pharmacology; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured
D017304:Annexin A5; D002352:Carrier Proteins; D016898:Interferon-alpha; D008565:Membrane Proteins; D010718:Phosphatidylserines; D049294:Phospholipid Transfer Proteins; D013439:Sulfhydryl Reagents; D005047:Etoposide; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases