Journal
MICROBIAL PATHOGENESIS
Volume 52, Issue 6, Pages 311-317Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.micpath.2012.02.007
Keywords
p53; ATM; Shiga toxin; Signaling; Mammalian cell; Apoptosis
Categories
Funding
- National Institute of Health (NIH)
- New Jersey Commission on Cancer Research (NJCCR)
- ICDDR, B: Centre for Health and Population
- Australian International Development Agency (AusAID), Australia
- Canadian International Development Agency (CIDA), Canada
- Centre endowment fund
- Department for International Development (DFID), UK
- Government of Bangladesh (GoB)
- Government of Sri Lanka
- Kingdom of Saudi Arabia (KSA)
- Government of the Netherlands
- Swedish International Development Cooperative Agency (Sida), Sweden
- Swiss Development Cooperation (SDC), Switzerland
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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 ST)(-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. Crown Copyright (c) 2012 Published by Elsevier Ltd. All rights reserved.
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