Bacterial intoxication evokes cellular senescence with persistent DNA damage and cytokine signalling

0347149 - ÚMG 2011 RIV GB eng J - Journal Article
Blažková, Hana - Krejčíková, Kateřina - Moudrý, Pavel - Frisan, T. - Hodný, Zdeněk - Bártek, Jiří
Bacterial intoxication evokes cellular senescence with persistent DNA damage and cytokine signalling.
Journal of Cellular and Molecular Medicine. Roč. 14, 1-2 (2009), s. 357-367. ISSN 1582-1838. E-ISSN 1582-4934
R&D Projects: GA AV ČR IAA500390501; GA ČR GA204/08/1418; GA ČR GA301/08/0353
Institutional research plan: CEZ:AV0Z50520514
Keywords : cellular senescence * DNA damage response * bacterial toxins
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 5.228, year: 2009

Cytolethal distending toxins (CDT) are proteins produced and secreted by facultative pathogenic strains of gram-negative bacteria with potentially genotoxic effects. We found both normal and cancer human cells exposed to CDT, surviving the acute phase of intoxication by Haemophilus ducreyi CDT, possess the main hallmarks of cellular senescence including persistently activated DNA damage signalling, expansion of promyelocytic leukaemia nuclear compartment and induced expression of several cytokines (e.g. IL-6, IL-8 and IL-24). We conclude that analogous to oncogenic, oxidative and replicative stresses, bacterial toxins represent another pathophysiological stimulus that induces premature senescence. Thus, the activation of cellular senescence as the anticancer barrier, together with evidence of chromosomal defects reported here, support the emerging genotoxic and potentially oncogenic effects of this group of bacterial toxins, and warrant further research of their role in human disease.
Permanent Link: http://hdl.handle.net/11104/0187989