Activation of p53/ATM-dependent DNA damage signaling pathway by shiga toxin in mammalian cells

Kaisar A. Talukder, Ishrat J. Azmi, K. Ahtesham Ahmed, M. Sabir Hossain, Yearul Kabir, Alejandro Cravioto, David Allen Sack, Alam Nur-E-Kamal

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)311-317
Number of pages7
JournalMicrobial Pathogenesis
Volume52
Issue number6
DOIs
Publication statusPublished - Jun 2012

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Keywords

  • Apoptosis
  • ATM
  • Mammalian cell
  • P53
  • Shiga toxin
  • Signaling

ASJC Scopus subject areas

  • Microbiology
  • Infectious Diseases

Cite this

Talukder, K. A., Azmi, I. J., Ahmed, K. A., Hossain, M. S., Kabir, Y., Cravioto, A., ... Nur-E-Kamal, A. (2012). Activation of p53/ATM-dependent DNA damage signaling pathway by shiga toxin in mammalian cells. Microbial Pathogenesis, 52(6), 311-317. https://doi.org/10.1016/j.micpath.2012.02.007