dc.contributor.author |
Pillay, Yogan
|
|
dc.contributor.author |
Phulukdaree, Alisa
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|
dc.contributor.author |
Nagiah, S.
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|
dc.contributor.author |
Chuturgoon, A.A.
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|
dc.date.accessioned |
2015-07-13T06:33:20Z |
|
dc.date.available |
2015-07-13T06:33:20Z |
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dc.date.issued |
2015-06 |
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dc.description.abstract |
Patulin (PAT), a mycotoxin contaminant of apples and apple products, has been implicated in nephrotoxicity. PAT depletes glutathione (GSH) and elevates reactive oxygen species (ROS). The antioxidant (AO) response is activated by Nuclear erythroid 2-related factor (NRF2) and enhanced by Silent information regulator 3 (SIRT3). The effects of PAT on these molecules have yet to be examined. We investigated the effects of PAT on AO response survival pathways in human embryonic kidney cells (HEK293).
PAT cytotoxicity on HEK293 cells was evaluated (MTT assay; 24 h; [0–100 μM]) to determine an IC50. GSH levels were measured using luminometry. Intracellular ROS was evaluated by flow cytometry. Protein expression of Keap1, NRF2, SIRT3 and PGC-1α was quantified by western blotting and gene expression of SOD2, CAT and GPx was evaluated by qPCR.
PAT caused a dose dependent decrease in HEK293 cell viability and a significant increase in levels of intracellular ROS (p = 0.0006). A significant increase in protein expression (p = 0.029) was observed. PAT increased gene expression of SOD2 and CAT (p = 0.0043), however, gene expression of GPx was significantly reduced (p = 0.0043). These results show the up-regulation of NRF2 mediated AO mechanisms in response to PAT toxicity. |
en_ZA |
dc.description.embargo |
2016-06-01 |
en_ZA |
dc.description.librarian |
hb2015 |
en_ZA |
dc.description.sponsorship |
National Research Foundation (Grant UID: 90102), and the UKZN College of Health Science |
en_ZA |
dc.description.uri |
http://www.elsevier.com/locate/toxicon |
en_ZA |
dc.identifier.citation |
Pillay, Y., Phulukdaree, A, Nagiah, S & Chuturgoon, AA 2015, 'Patulin triggers NRF2-mediated survival mechanisms in kidney cells', Toxicon, vol. 99, pp.1-5. |
en_ZA |
dc.identifier.issn |
0041-0101 (print) |
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dc.identifier.issn |
1879-3150 (online) |
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dc.identifier.other |
10.1016/j.toxicon.2015.03.004 |
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dc.identifier.uri |
http://hdl.handle.net/2263/47961 |
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dc.language.iso |
en |
en_ZA |
dc.publisher |
Elsevier |
en_ZA |
dc.rights |
© 2015 Elsevier Ltd. All rights reserved. Notice : this is the author’s version of a work that was accepted for publication in Toxicon. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Toxicon, vol. 99, pp. 1-5, 2015. doi : 10.1016/j.toxicon.2015.03.004 |
en_ZA |
dc.subject |
Patulin (PAT) |
en_ZA |
dc.subject |
Glutathione (GSH) |
en_ZA |
dc.subject |
Reactive oxygen species (ROS) |
en_ZA |
dc.subject |
Nuclear erythroid 2-related factor (NRF2) |
en_ZA |
dc.subject |
Antioxidant |
en_ZA |
dc.subject |
Silent information regulator 3 (SIRT3) |
en_ZA |
dc.subject |
Human embryonic kidney cells (HEK293) |
en_ZA |
dc.title |
Patulin triggers NRF2-mediated survival mechanisms in kidney cells |
en_ZA |
dc.type |
Postprint Article |
en_ZA |