Paradoxical role of 3-methyladenine in pyocyanin-induced toxicity in 1321N1 astrocytoma and SH-SY5Y neuroblastoma cells

McFarland, Amelia J., Grant, Gary D., Perkins, Anthony V., Flegg, Cameron, Davey, Andrew K., Allsopp, Tristan J., Renshaw, Gillian, Kavanagh, Justin, McDermott, Catherine M. and Anoopkumar-Dukie, Shailendra (2013) Paradoxical role of 3-methyladenine in pyocyanin-induced toxicity in 1321N1 astrocytoma and SH-SY5Y neuroblastoma cells. International Journal of Toxicology, 32 3: 209-218. doi:10.1177/1091581813482146

Author McFarland, Amelia J.
Grant, Gary D.
Perkins, Anthony V.
Flegg, Cameron
Davey, Andrew K.
Allsopp, Tristan J.
Renshaw, Gillian
Kavanagh, Justin
McDermott, Catherine M.
Anoopkumar-Dukie, Shailendra
Title Paradoxical role of 3-methyladenine in pyocyanin-induced toxicity in 1321N1 astrocytoma and SH-SY5Y neuroblastoma cells
Journal name International Journal of Toxicology   Check publisher's open access policy
ISSN 1091-5818
Publication date 2013-05
Sub-type Article (original research)
DOI 10.1177/1091581813482146
Volume 32
Issue 3
Start page 209
End page 218
Total pages 10
Place of publication Thousand Oaks, CA, United States
Publisher Sage Publications
Collection year 2014
Language eng
Formatted 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 μmol/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 μmol/L) significantly increased the production of interleukin-8 (IL-8), prostaglandin E2 (PGE2), and leukotriene B4 (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, PGE2, 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, PGE2, and LTB4 production.
Keyword Autophagy
Pseudomonas-aeruginosa meningitis
Respiratory epithelium
Oxidative stress
Lipoxin A(4)
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
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