Document Detail


Caspase-dependent apoptosis and -independent poly(ADP-ribose) polymerase cleavage induced by transforming growth factor beta1.
MedLine Citation:
PMID:  14643888     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Apoptosis is an important cell suicide program which involves the caspases activation and is implicated in physiological and pathological processes. Poly(ADP-ribose) polymerase (PARP) cleavage is often associated with apoptosis and has been served as one hallmark of apoptosis and caspase activation. In this study, we aimed to determine TGF-beta1-induced apoptosis and to examine the involvement of caspases and its relationship with PARP cleavage. TGF-beta1 induces strong apoptosis of AML-12 cells which can be detected by DNA fragmentation, FACS, and morphological assays. Z-VAD-fmk, a selective caspase inhibitor, partially inhibits the TGF-beta1-induced apoptosis; but has no effect on TGF-beta1-induced DNA fragmentation and PARP cleavage. However, BD-fmk, a broad-spectrum caspase inhibitor, completely suppresses TGF-beta1-induced apoptosis, but unexpectedly does not inhibit TGF-beta1-induced PARP cleavage. Furthermore, Z-VAD-fmk treatment is able to completely inhibit the daunorubicin-induced apoptosis in A-431 cells, but only slightly blocks the daunorubicin-induced PARP cleavage, whereas BD-fmk can inhibit both daunorubicin-induced apoptosis and PARP cleavage completely. In addition, we observed that both TGF-beta1-induced apoptosis and PARP degradation in AML-12 cells can be completely blocked by inhibiting the protein synthesis with cycloheximide. These results demonstrate for the first time that TGF-beta1-induced caspase-dependent apoptosis is associated with caspase-independent PARP cleavage that requires the TGF-beta1-induced synthesis of new proteins. The results indicate that caspase-3 is not a major caspase involved in TGF-beta1-induced apoptosis in AML-12 cells, and is not required for apoptosis-associated DNA fragmentation. The results also suggest that PARP cleavage may occur as an independent event that can be disassociated with cell apoptosis.
Authors:
Yanan Yang; Sheng Zhao; Jianguo Song
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The international journal of biochemistry & cell biology     Volume:  36     ISSN:  1357-2725     ISO Abbreviation:  Int. J. Biochem. Cell Biol.     Publication Date:  2004 Feb 
Date Detail:
Created Date:  2003-12-03     Completed Date:  2004-08-05     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9508482     Medline TA:  Int J Biochem Cell Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  223-34     Citation Subset:  IM    
Affiliation:
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, 200031, Shanghai, China.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Chloromethyl Ketones / pharmacology
Animals
Apoptosis*
Caspases / metabolism*
Cell Line
Cell Separation
Cycloheximide / pharmacology
DNA Fragmentation
Daunorubicin / pharmacology
Enzyme Inhibitors / pharmacology
Flow Cytometry
Hepatocytes / pathology
Immunoblotting
Mice
Microscopy, Fluorescence
Poly(ADP-ribose) Polymerases / metabolism*
Protein Kinase C / metabolism
Protein Kinase C-delta
Protein Synthesis Inhibitors / pharmacology
Time Factors
Transforming Growth Factor beta / metabolism*
Transforming Growth Factor beta1
Chemical
Reg. No./Substance:
0/Amino Acid Chloromethyl Ketones; 0/Enzyme Inhibitors; 0/Protein Synthesis Inhibitors; 0/Tgfb1 protein, mouse; 0/Transforming Growth Factor beta; 0/Transforming Growth Factor beta1; 0/benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; 20830-81-3/Daunorubicin; 66-81-9/Cycloheximide; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 2.7.1.-/Prkcd protein, mouse; EC 2.7.11.13/Protein Kinase C; EC 2.7.11.13/Protein Kinase C-delta; EC 3.4.22.-/Caspases

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