Document Detail

The p53/HSP70 inhibitor, 2-phenylethynesulfonamide, causes oxidative stress, unfolded protein response and apoptosis in rainbow trout cells.
MedLine Citation:
PMID:  24270669     Owner:  NLM     Status:  Publisher    
The effect of 2-phenylethynesulfonamide (PES), which is a p53 and HSP70 inhibitor in mammalian cells, was studied on the rainbow trout (Oncorhynchus mykiss) gill epithelial cell line, RTgill-W1, in order to evaluate PES as a tool for understanding the cellular survival pathways operating in fish. As judged by three viability assays, fish cells were killed by 24h exposures to PES, but cell death was blocked by the anti-oxidant N-acetylcysteine (NAC). Cell death had several hallmarks of apoptosis: DNA laddering, nuclear fragmentation, Annexin V staining, mitochondrial membrane potential decline, and caspases activation. Reactive oxygen species (ROS) production peaked in several hours after the addition of PES and before cell death. HSP70 and BiP levels were higher in cultures treated with PES for 24h, but this was blocked by NAC. As well, PES treatment caused HSP70, BiP and p53 to accumulate in the detergent-insoluble fraction, and this too was prevented by NAC. Of several possible scenarios to explain the results, the following one is the simplest. PES enhances the generation of ROS, possibly by inhibiting the anti-oxidant actions of p53 and HSP70. ER stress arises from the ROS and from PES inhibiting the chaperone activities of HSP70. The ER stress in turn initiates the unfolded protein response (UPR), but this fails to restore ER homeostasis so proteins aggregate and cells die. Despite these multiple actions, PES should be useful for studying fish cellular survival pathways.
Fanxing Zeng; Catherine Tee; Michelle Liu; James P Sherry; Brian Dixon; Bernard P Duncker; Niels C Bols
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-11-2
Journal Detail:
Title:  Aquatic toxicology (Amsterdam, Netherlands)     Volume:  146C     ISSN:  1879-1514     ISO Abbreviation:  Aquat. Toxicol.     Publication Date:  2013 Nov 
Date Detail:
Created Date:  2013-11-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8500246     Medline TA:  Aquat Toxicol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  45-51     Citation Subset:  -    
Copyright Information:
Copyright © 2013 Elsevier B.V. All rights reserved.
Department of Biology, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada.
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