Erythropoietin activates caspase-3 and downregulates CAD during erythroid differentiation in TF-1 cells – A protection mechanism against DNA fragmentation

The involvement of caspase-3 and its failure in the induction of DNA fragmentation during erythropoiesis were investigated with TF-1 cells. During erythroid differentiation, caspase-3 activation and cleavage of caspase-3 substrates such as ICAD (inhibitor of caspase-activated DNase) were detected wi...

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Bibliographic Details
Published in:FEBS letters 2006-04, Vol.580 (8), p.1965-1970
Main Authors: Lui, Julian Chun-Kin, Kong, Siu-Kai
Format: Article
Language:English
Subjects:
Apoptosis
Apoptosis Regulatory Proteins
CAD
Caspase 3
Caspase Inhibitors
caspase-activated DNase
Caspases - metabolism
Cell Differentiation
Cells, Cultured
Deoxyribonucleases - genetics
Deoxyribonucleases - metabolism
DNA fragmentation
DNA Fragmentation - drug effects
Down-Regulation - genetics
Enzyme Activation
EPO
Erythroid Cells - cytology
Erythroid Cells - enzymology
Erythroid differentiation
Erythropoiesis - physiology
erythropoietin
Erythropoietin - pharmacology
GADPH
Gene Expression
glyceraldehyde-3-phosphate dehydrogenase
glycophorin A
GM-CSF
GPA
granulocyte-macrophage colony stimulating factor
hemoglobin
Humans
ICAD
inhibitor of the caspase-activated DNase
MAb
monoclonal antibody
PARP
phosphatidylserine
poly (ADP-ribose) polymerase
Poly(ADP-ribose) Polymerases
propidium iodide
Proteins - genetics
Proteins - metabolism
Recombinant Proteins
RNA, Messenger - genetics
RNA, Messenger - metabolism
staurosporine
STS
terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling
TUNEL
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Summary:The involvement of caspase-3 and its failure in the induction of DNA fragmentation during erythropoiesis were investigated with TF-1 cells. During erythroid differentiation, caspase-3 activation and cleavage of caspase-3 substrates such as ICAD (inhibitor of caspase-activated DNase) were detected without concomitant phosphatidyl-serine (PS) externalization and DNA fragmentation. These observations are in contrast to our understanding that DNA is degraded by CAD (caspase-activated DNase) when ICAD is cleaved by caspase-3. Our study demonstrates that CAD is downregulated at the mRNA and protein level during the erythroid differentiation in TF-1 cells. This provides a mechanism for the first time how cells avoid DNA fragmentation with activated caspase-3.
ISSN:0014-5793
1873-3468
DOI:10.1016/j.febslet.2006.02.059