Document Detail


Activation of p53/ATM-dependent DNA damage signaling pathway by shiga toxin in mammalian cells.
MedLine Citation:
PMID:  22406215     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
In this report, we studied the role of DNA damage signaling pathway in shiga toxin (STX)-induced mammalian cell death. Shiga toxin 1 exhibited cytotoxic activity in different mammalian cells such as HeLa cells, mouse embryo fibroblasts, and Caco-2 cells (a human intestinal primary fibroblast cell line). STX-1 was found to induce the release of cytochrome c from the mitochondria, nuclear condensation, and fragmentation of chromosomal DNA. STX-1 activated DNA damage signaling as determined by induction of H2AX phosphorylation and cleavage of PARP. Inhibition of caspase-3 reduced STX-1-induced phosphorylation of H2AX and nuclear condensation. It was also found that STX-1-induced p53 expression, and activated ATM in mammalian cells. STX-1-induced nuclear condensation significantly reduced in p53-, and ATM-knockout cells suggesting an involvement of p53 and ATM in transducing signals produced by STX in inducing apoptosis in mammalian cells. This is the first demonstration of involvement of ATM/p53 in STX-inducing mammalian cell death.
Authors:
Kaisar Ali Talukder; Ishrat J Azmi; K Ahtesham Ahmed; M Sabir Hossain; Yearul Kabir; Alejandro Cravioto; David Sack; Alam Nur-E-Kamal
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-3-2
Journal Detail:
Title:  Microbial pathogenesis     Volume:  -     ISSN:  1096-1208     ISO Abbreviation:  -     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-3-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8606191     Medline TA:  Microb Pathog     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier Ltd.
Affiliation:
ICDDR, B: Centre for Health and Population Research, GPO Box-128, Dhaka 1000, Bangladesh.
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