LPS-induced delayed preconditioning is mediated by Hsp90 and involves the heat shock response in mouse kidney.
We and others demonstrated previously that preconditioning with endotoxin (LPS) protected from a subsequent lethal LPS challenge or from renal ischemia-reperfusion injury (IRI). LPS is effective in evoking the heat shock response, an ancient and essential cellular defense mechanism, which plays a ro...
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doaj-244dd8c4bbad449fbede8d5c0cdde9f72020-11-25T01:59:16ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0193e9200410.1371/journal.pone.0092004LPS-induced delayed preconditioning is mediated by Hsp90 and involves the heat shock response in mouse kidney.Tamás KaucsárCsaba BodorMária GodóCsaba SzalayCsaba RévészZalán NémethMiklós MózesGábor SzénásiLászló RosivallCsaba SőtiPéter HamarWe and others demonstrated previously that preconditioning with endotoxin (LPS) protected from a subsequent lethal LPS challenge or from renal ischemia-reperfusion injury (IRI). LPS is effective in evoking the heat shock response, an ancient and essential cellular defense mechanism, which plays a role in resistance to, and recovery from diseases. Here, by using the pharmacological Hsp90 inhibitor novobiocin (NB), we investigated the role of Hsp90 and the heat shock response in LPS-induced delayed renal preconditioning.Male C57BL/6 mice were treated with preconditioning (P: 2 mg/kg, i.p.) and subsequent lethal (L: 10 mg/kg, i.p.) doses of LPS alone or in combination with NB (100 mg/kg, i.p.). Controls received saline (C) or NB.Preconditioning LPS conferred protection from a subsequent lethal LPS treatment. Importantly, the protective effect of LPS preconditioning was completely abolished by a concomitant treatment with NB. LPS induced a marked heat shock protein increase as demonstrated by Western blots of Hsp70 and Hsp90. NB alone also stimulated Hsp70 and Hsp90 mRNA but not protein expression. However, Hsp70 and Hsp90 protein induction in LPS-treated mice was abolished by a concomitant NB treatment, demonstrating a NB-induced impairment of the heat shock response to LPS preconditioning.LPS-induced heat shock protein induction and tolerance to a subsequent lethal LPS treatment was prevented by the Hsp90 inhibitor, novobiocin. Our findings demonstrate a critical role of Hsp90 in LPS signaling, and a potential involvement of the heat shock response in LPS-induced preconditioning.http://europepmc.org/articles/PMC3960147?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Tamás Kaucsár Csaba Bodor Mária Godó Csaba Szalay Csaba Révész Zalán Németh Miklós Mózes Gábor Szénási László Rosivall Csaba Sőti Péter Hamar |
spellingShingle |
Tamás Kaucsár Csaba Bodor Mária Godó Csaba Szalay Csaba Révész Zalán Németh Miklós Mózes Gábor Szénási László Rosivall Csaba Sőti Péter Hamar LPS-induced delayed preconditioning is mediated by Hsp90 and involves the heat shock response in mouse kidney. PLoS ONE |
author_facet |
Tamás Kaucsár Csaba Bodor Mária Godó Csaba Szalay Csaba Révész Zalán Németh Miklós Mózes Gábor Szénási László Rosivall Csaba Sőti Péter Hamar |
author_sort |
Tamás Kaucsár |
title |
LPS-induced delayed preconditioning is mediated by Hsp90 and involves the heat shock response in mouse kidney. |
title_short |
LPS-induced delayed preconditioning is mediated by Hsp90 and involves the heat shock response in mouse kidney. |
title_full |
LPS-induced delayed preconditioning is mediated by Hsp90 and involves the heat shock response in mouse kidney. |
title_fullStr |
LPS-induced delayed preconditioning is mediated by Hsp90 and involves the heat shock response in mouse kidney. |
title_full_unstemmed |
LPS-induced delayed preconditioning is mediated by Hsp90 and involves the heat shock response in mouse kidney. |
title_sort |
lps-induced delayed preconditioning is mediated by hsp90 and involves the heat shock response in mouse kidney. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2014-01-01 |
description |
We and others demonstrated previously that preconditioning with endotoxin (LPS) protected from a subsequent lethal LPS challenge or from renal ischemia-reperfusion injury (IRI). LPS is effective in evoking the heat shock response, an ancient and essential cellular defense mechanism, which plays a role in resistance to, and recovery from diseases. Here, by using the pharmacological Hsp90 inhibitor novobiocin (NB), we investigated the role of Hsp90 and the heat shock response in LPS-induced delayed renal preconditioning.Male C57BL/6 mice were treated with preconditioning (P: 2 mg/kg, i.p.) and subsequent lethal (L: 10 mg/kg, i.p.) doses of LPS alone or in combination with NB (100 mg/kg, i.p.). Controls received saline (C) or NB.Preconditioning LPS conferred protection from a subsequent lethal LPS treatment. Importantly, the protective effect of LPS preconditioning was completely abolished by a concomitant treatment with NB. LPS induced a marked heat shock protein increase as demonstrated by Western blots of Hsp70 and Hsp90. NB alone also stimulated Hsp70 and Hsp90 mRNA but not protein expression. However, Hsp70 and Hsp90 protein induction in LPS-treated mice was abolished by a concomitant NB treatment, demonstrating a NB-induced impairment of the heat shock response to LPS preconditioning.LPS-induced heat shock protein induction and tolerance to a subsequent lethal LPS treatment was prevented by the Hsp90 inhibitor, novobiocin. Our findings demonstrate a critical role of Hsp90 in LPS signaling, and a potential involvement of the heat shock response in LPS-induced preconditioning. |
url |
http://europepmc.org/articles/PMC3960147?pdf=render |
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