BCL-2 family expression in human neutrophils during delayed and accelerated apoptosis.
The human neutrophil spontaneously undergoes apoptosis, but this type of cell death can be delayed or accelerated by a wide variety of agents. There are wide discrepancies in the literature regarding the expression of the Bcl-2 family of proteins in human neutrophils. Here, we show that A1, Mcl-1, Bcl-X(L), and Bad are major transcripts in human neutrophils and that levels of these transcripts are cytokine regulated. However, no Bcl-X(L) protein was detected in Western blots. Protein levels for the proapoptotic proteins Bad, Bax, Bak, and Bik remained constant during culture, despite changes in the levels of mRNA for these gene products. These proapoptotic proteins were extremely stable, having very long half-lives. In contrast, A1 and Mcl-1 transcripts were extremely unstable (with approximately 3-h half-lives), and Mcl-1 protein was also subject to rapid turnover. These results indicate that neutrophil survival is regulated by the inducible expression of the short-lived Mcl-1 and possibly the A1 gene products. In the absence of their continued expression, these prosurvival gene products are rapidly turned over, and then the activity of the stable death proteins predominates and promotes apoptosis.
Moulding
D A
DA
The University of Liverpool, School of Biological Sciences, Life Sciences Building, Crown Street, Liverpool L69 7ZB, United Kingdom.
Akgul
C
C
Derouet
M
M
White
M R
MR
Edwards
S W
SW
D000328:Adult; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D003513:Cycloheximide / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D003609:Dactinomycin / Q000494:pharmacology; D004804:Eosinophils / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D019254:Genes, bcl-2; D005912:Gliotoxin / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006207:Half-Life; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D024101:Mitochondrial Proteins; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D014176:Protein Biosynthesis; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011506:Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051818:Replication Protein C; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D051020:bcl-X Protein
D051017:Apoptosis Regulatory Proteins; C494819:BAD protein, human; C494772:BAK1 protein, human; C494826:BAX protein, human; C494811:BCL2L1 protein, human; C096820:BIK protein, human; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D016328:NF-kappa B; D009363:Neoplasm Proteins; D019384:Nucleic Acid Synthesis Inhibitors; D011500:Protein Synthesis Inhibitors; D011506:Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D051020:bcl-X Protein; D003609:Dactinomycin; D005912:Gliotoxin; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003513:Cycloheximide; D051818:Replication Protein C