Journal article
Paradoxical Role of 3-Methyladenine in Pyocyanin-Induced Toxicity in 1321N1 Astrocytoma and SH-SY5Y Neuroblastoma Cells
International Journal of Toxicology, Vol.32(3), pp.209-218
2013
PMID: 23525265
Abstract
The role of autophagy in pyocyanin (PCN)-induced toxicity in the central nervous system (CNS) remains unclear, with only evidence from our group identifying it as a mechanism underlying toxicity in 1321N1 astrocytoma cells. Therefore, the aim of this study was to further examine the role of autophagy in PCN-induced toxicity in the CNS. To achieve this, we exposed 1321N1 astrocytoma and SH-SY5Y neuroblastoma cells to PCN (0-100 mu mol/L) and tested the contribution of autophagy by measuring the impact of the autophagy inhibitor 3-methyladenine (3-MA) using a series of biochemical and molecular markers. Pretreatment of 1321N1 astrocytoma cells with 3-MA (5 mmol/L) decreased the PCN-induced acidic vesicular organelle and autophagosome formation as measured using acridine orange and green fluorescent protein-LC3 -LC3 fluorescence, respectively. Furthermore, 3-MA (5 mmol/L) significantly protected 1321N1 astrocytoma cells against PCN-induced toxicity. In contrast pretreatment with 3-MA (5 mmol/L) increased PCN-induced toxicity in SH-SY5Y neuroblastoma cells. Given the influence of autophagy in inflammatory responses, we investigated whether the observed effects in this study involved inflammatory mediators. The PCN (100 mu mol/L) significantly increased the production of interleukin-8 (IL-8), prostaglandin E-2 (PGE(2)), and leukotriene B-4 (LTB4) in both cell lines. Consistent with its paradoxical role in modulating PCN-induced toxicity, 3-MA (5 mmol/L) significantly reduced the PCN-induced production of IL-8, PGE(2), and LTB4 in 1321N1 astrocytoma cells but augmented their production in SH-SY5Y neuroblastoma cells. In conclusion, we show here for the first time the paradoxical role of autophagy in mediating PCN-induced toxicity in 1321N1 astrocytoma and SH-SY5Y neuroblastoma cells and provide novel evidence that these actions may be mediated by effects on IL-8, PGE(2), and LTB4 production.
Details
- Title
- Paradoxical Role of 3-Methyladenine in Pyocyanin-Induced Toxicity in 1321N1 Astrocytoma and SH-SY5Y Neuroblastoma Cells
- Authors
- Amelia J. McFarland (Author) - Griffith UniversityGary D. Grant (Author) - Griffith UniversityAnthony V. Perkins (Author) - Griffith UniversityCameron Flegg (Author) - Griffith UniversityAndrew K. Davey (Author) - Griffith UniversityTristan J. Allsopp (Author) - University of QueenslandGillian Renshaw (Author) - Griffith UniversityJustin Kavanagh (Author) - Griffith UniversityCatherine M. McDermott (Author) - Bond UniversityShailendra Anoopkumar-Dukie (Author) - Griffith University
- Publication details
- International Journal of Toxicology, Vol.32(3), pp.209-218
- Publisher
- Sage Publications Inc.
- DOI
- 10.1177/1091581813482146
- ISSN
- 1092-874X
- PMID
- 23525265
- Organisation Unit
- School of Health and Behavioural Sciences - Legacy; School of Health
- Language
- English
- Record Identifier
- 99685194902621
- Output Type
- Journal article
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- Domestic collaboration
- Web Of Science research areas
- Pharmacology & Pharmacy
- Toxicology
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Source: InCites