Document Detail


Apaf-1- and Caspase-8-independent apoptosis.
MedLine Citation:
PMID:  23197294     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Two major apoptosis pathways, the mitochondrial and death receptor pathways, are well recognized. Here we established cell lines from the fetal thymus of Apaf-1-, Caspase-9-, or Bax/Bak-deficient mice. These cell lines were resistant to apoptosis induced by DNA-damaging agents, RNA or protein synthesis inhibitors, or stress in the endoplasmic reticulum. However, they underwent efficient apoptosis when treated with kinase inhibitors such as staurosporine and H-89, indicating that these inhibitors induce a caspase-dependent apoptosis that is different from the mitochondrial pathway. CrmA, a Caspase-8 inhibitor, did not prevent staurosporine-induced apoptosis of fetal thymic cell lines, suggesting that the death receptor pathway was also not involved in this process. The staurosporine-induced cell death was inhibited by okadaic acid, a serine/threonine phosphatase inhibitor, suggesting that dephosphorylation of a proapoptotic molecule triggered the death process, or that phosphorylation of an antiapoptotic molecule could block the process. Cells of various types (fetal thymocytes, bone marrows, thymocytes, and splenocytes), but not embryonic fibroblasts, were sensitive to the noncanonical staurosporine-induced apoptosis, suggesting that the noncanonical apoptosis pathway is tissue specific.
Authors:
T Imao; S Nagata
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-11-30
Journal Detail:
Title:  Cell death and differentiation     Volume:  20     ISSN:  1476-5403     ISO Abbreviation:  Cell Death Differ.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-15     Completed Date:  2013-06-21     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  9437445     Medline TA:  Cell Death Differ     Country:  England    
Other Details:
Languages:  eng     Pagination:  343-52     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects*
Apoptotic Protease-Activating Factor 1 / deficiency,  genetics,  metabolism*
Caspase 8 / chemistry,  metabolism*
Caspase 9 / deficiency,  genetics,  metabolism
Cells, Cultured
Fibroblasts / cytology,  metabolism
Isoquinolines / pharmacology
Mice
Mice, Inbred C57BL
Mice, Knockout
Okadaic Acid / pharmacology
Protein Kinase Inhibitors / pharmacology*
Staurosporine / pharmacology
Sulfonamides / pharmacology
Thymocytes / cytology,  metabolism
bcl-2 Homologous Antagonist-Killer Protein / deficiency,  genetics,  metabolism
bcl-2-Associated X Protein / deficiency,  genetics,  metabolism
Chemical
Reg. No./Substance:
0/Apaf1 protein, mouse; 0/Apoptotic Protease-Activating Factor 1; 0/Isoquinolines; 0/Protein Kinase Inhibitors; 0/Sulfonamides; 0/bcl-2 Homologous Antagonist-Killer Protein; 0/bcl-2-Associated X Protein; 127243-85-0/N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; 1W21G5Q4N2/Okadaic Acid; EC 3.4.22.-/Caspase 8; EC 3.4.22.-/Caspase 9; H88EPA0A3N/Staurosporine
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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