Journal article
Pyocyanin-induced toxicity in A549 respiratory cells is causally linked to oxidative stress
Toxicology in Vitro, Vol.25(7), pp.1353-1358
2011
PMID: 21596130
Abstract
Pyocyanin, a virulence factor produced by Pseudomonas aeruginosa, has many damaging effects on mammalian cells. Several lines of evidence suggest that this damage is primarily mediated by its ability to generate ROS and deplete host antioxidant defence mechanisms. However, a causal role for oxidative stress has not yet been demonstrated conclusively. Parallel measures of ROS production, antioxidant levels and cytotoxicity provide convincing evidence that pyocyanin-induced cytotoxicity in A549 respiratory cells is mediated by acute ROS production and subsequent oxidative stress. Pyocyanin increased ROS levels in A549 cells as measured by the fluorescent H2O2 probes Amplex Red and DCFH-DA. These effects were attenuated by the antioxidant N-acetylcysteine. Furthermore, pyocyanin-induced depletion of intracellular GSH levels 24 h after exposure was also prevented by pre-treatment of cells with NAC. Under these conditions, NAC protected cells against pyocyanin-induced cytotoxicity as measured by resazurin reduction to resorufin and viable cell counts, strongly supporting a causal role for oxidative stress. Finally, we also show that pyocyanin-induced activation of the immune and inflammatory transcription factor NF-κB in A549 cells is likely mediated by increased ROS. This increased understanding of mechanisms underlying pyocyanin-induced cytotoxicity may ultimately lead to better strategies for reducing the virulence associated with chronic P. aeruginosa infection.
Details
- Title
- Pyocyanin-induced toxicity in A549 respiratory cells is causally linked to oxidative stress
- Authors
- Lee S. Gloyne (Author) - Griffith UniversityGary D. Grant (Author) - Griffith UniversityAnthony V. Perkins (Author) - Griffith UniversityKatie L. Powell (Author) - Griffith UniversityCatherine M. McDermott (Author) - Bond UniversityPeter V. Johnson (Author) - Bond UniversityGregory J. Anderson (Author) - QIMR Berghofer Medical Research InstituteMilton Kiefel (Author) - Griffith UniversityShailendra Anoopkumar-Dukie (Corresponding Author) - Griffith University
- Publication details
- Toxicology in Vitro, Vol.25(7), pp.1353-1358
- Publisher
- Elsevier Ltd
- DOI
- 10.1016/j.tiv.2011.05.004
- ISSN
- 1879-3177
- PMID
- 21596130
- Organisation Unit
- School of Health and Behavioural Sciences - Legacy; School of Health
- Language
- English
- Record Identifier
- 99685195302621
- Output Type
- Journal article
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- Toxicology
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Source: InCites