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Heat shock protein 70 inhibits the nuclear import of apoptosis-inducing factor to avoid DNA fragmentation in TF-1 cells during erythropoiesis |
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| Authors: | Lui Julian Chun-Kin Kong Siu-Kai |
| Institution: | Department of Biochemistry, The Chinese University of Hong Kong, Shatin, Hong Kong, China. |
| Abstract: | Loss of mitochondrial membrane potential (DeltaPsi(m)) and release of AIF (apoptosis-inducing factor) from mitochondria are key steps in apoptosis. In TF-1 model, DeltaPsi(m) was depolarized with AIF release during erythroid development. Yet, no DNA fragmentation was observed. When DeltaPsi(m) depolarization had been blocked, erythropoiesis was suppressed. Interestingly, heat shock protein 70 (Hsp70) was found transiently upregulated during depolarization and it retained AIF in the cytosol to avoid DNA damages. When Hsp inhibitor was added, DNA fragmentation occurred. We show this mechanism for the first time in erythropoiesis how cells with DeltaPsi(m) depolarization and AIF release escape apoptosis. |
| Keywords: | AIF apoptosis-inducing factor CAD caspase-activated DNase CCCP carbonyl cyanide m-chlorophenylhydrazone CyA cyclosporin A EPO erythropoietin GM-CSF granulocyte-macrophage colony stimulating factor Hsp70 heat shock protein 70 ICAD inhibitor of CAD JC-1 5 5′ 6 6′-tetrachloro-1 1′ 3 3′-tetraethylbenzimidazolcarbocyanine iodide KNK437 N-formyl-3 4-methylenedioxy-benzylidene-gamma-butyrolactam MAb monoclonal antibody STS staurosporine TMRM tetramethylrhodamine methyl ester TdT terminal deoxynucleotide transferase TUNEL terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling ΔΨm mitochondrial membrane potential |
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