Show simple item record Hosszú, Ádám Antal, Zsuzsanna Lénárt, Lilla Hodrea, Judit Kőszegi, Sándor Balogh, Dóra Bianka Bánki, Nóra Fanni Wágner, László József Dénes, Ádám Hamar, Péter Degrell P Vannay, Ádám Szabó, Attila Fekete, Andrea 2017-03-27T12:39:53Z 2017-03-27T12:39:53Z 2017
dc.identifier.citation pagination=152-165; journalVolume=28; journalIssueNumber=1; journalTitle=JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY;
dc.identifier.uri doi:10.1681/ASN.2015070772
dc.description.abstract Mechanisms of renal ischemia-reperfusion injury remain unresolved, and effective therapies are lacking. We previously showed that dehydroepiandrosterone protects against renal ischemia-reperfusion injury in male rats. Here, we investigated the potential role ofsigma1-receptor activation in mediating this protection. In rats, pretreatment with either dehydroepiandrosterone or fluvoxamine, a high-affinitysigma1-receptor agonist, improved survival, renal function and structure, and the inflammatory response after sublethal renal ischemia-reperfusion injury. In human proximal tubular epithelial cells, stimulation by fluvoxamine or oxidative stress caused thesigma1-receptor to translocate from the endoplasmic reticulum to the cytosol and nucleus. Fluvoxamine stimulation in these cells also activated nitric oxide production that was blocked bysigma1-receptor knockdown or Akt inhibition. Similarly, in the postischemic rat kidney,sigma1-receptor activation by fluvoxamine triggered the Akt-nitric oxide synthase signaling pathway, resulting in time- and isoform-specific endothelial and neuronal nitric oxide synthase activation and nitric oxide production. Concurrently, intravital two-photon imaging revealed prompt peritubular vasodilation after fluvoxamine treatment, which was blocked by thesigma1-receptor antagonist or various nitric oxide synthase blockers. In conclusion, in this rat model of ischemia-reperfusion injury,sigma1-receptor agonists improved postischemic survival and renal functionviaactivation of Akt-mediated nitric oxide signaling in the kidney. Thus,sigma1-receptor activation might provide a therapeutic option for renoprotective therapy.
dc.relation.ispartof urn:issn:1046-6673
dc.title Sigma1-Receptor Agonism Protects against Renal Ischemia-Reperfusion Injury
dc.type Journal Article 2017-02-03T12:02:12Z
dc.language.rfc3066 en
dc.identifier.mtmt 3049309
dc.identifier.pubmed 27056295
dc.contributor.department SE/AOK/K/I. Sz. Gyermekgyógyászati Klinika
dc.contributor.department SE/AOK/K/ISZGYK/MTA-SE Gyermekgyógyászati és Nephrológiai Kutatócsoport
dc.contributor.department SE/AOK/K/ISZGYK/MTA-SE Lendület Diabétesz Kutatócsoport
dc.contributor.department SE/AOK/I/Kórélettani Intézet
dc.contributor.department SE/AOK/K/Transzplantációs és Sebészeti Klinika
dc.contributor.institution Semmelweis Egyetem

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