| Dokumentenart: | Artikel | ||||
|---|---|---|---|---|---|
| Titel eines Journals oder einer Zeitschrift: | American Journal of Physiology-Renal Physiology | ||||
| Verlag: | AMER PHYSIOLOGICAL SOC | ||||
| Ort der Veröffentlichung: | BETHESDA | ||||
| Band: | 298 | ||||
| Nummer des Zeitschriftenheftes oder des Kapitels: | 1 | ||||
| Seitenbereich: | F196-F204 | ||||
| Datum: | 2010 | ||||
| Institutionen: | Medizin > Lehrstuhl für Anästhesiologie Biologie und Vorklinische Medizin > Institut für Physiologie Chemie und Pharmazie > Institut für Pharmazie > Lehrstuhl Pharmakologie und Toxikologie (Prof. Schlossmann, ehemals Prof. Seifert) | ||||
| Identifikationsnummer: |
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| Stichwörter / Keywords: | ACUTE KIDNEY INJURY; SEPTIC SHOCK; SEVERE INFLAMMATION; NITRIC-OXIDE; TNF-ALPHA; ACTIVATION; ENDOTOXEMIA; RATS; MICE; TRANSPORTERS; cecal ligation and puncture; kidney; inflammation; vasopressin; cytokines | ||||
| Dewey-Dezimal-Klassifikation: | 500 Naturwissenschaften und Mathematik > 540 Chemie 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin 600 Technik, Medizin, angewandte Wissenschaften > 615 Pharmazie | ||||
| Status: | Veröffentlicht | ||||
| Begutachtet: | Ja, diese Version wurde begutachtet | ||||
| An der Universität Regensburg entstanden: | Ja | ||||
| Dokumenten-ID: | 66481 |
Web of ScienceZusammenfassung
Hocherl K, Schmidt C, Kurt B, Bucher M. Inhibition of NF-kappa B ameliorates sepsis-induced downregulation of aquaporin-2/V-2 receptor expression and acute renal failure in vivo. Am J Physiol Renal Physiol 298: F196-F204, 2010. First published October 14, 2009; doi:10.1152/ajprenal.90607.2008.-Acute renal failure (ARF) is frequently associated with polyuria and urine concentration defects and it ...
Zusammenfassung
Hocherl K, Schmidt C, Kurt B, Bucher M. Inhibition of NF-kappa B ameliorates sepsis-induced downregulation of aquaporin-2/V-2 receptor expression and acute renal failure in vivo. Am J Physiol Renal Physiol 298: F196-F204, 2010. First published October 14, 2009; doi:10.1152/ajprenal.90607.2008.-Acute renal failure (ARF) is frequently associated with polyuria and urine concentration defects and it is a severe complication of sepsis because it increases the mortality rate. Inhibition of NF-kappa B activation has been suggested to provide a useful strategy for the treatment of septic shock. However, the impact on sepsis-induced ARF is still unclear. Therefore, we examined the effect of pyrrolidine dithiocarbamate (PDTC) and of small interfering RNA (siRNA) silencing NF-kappa B p50/p105 on sepsis-induced downregulation of vasopressin V-2 receptors and aquaporin (AQP)-2 channels using a cecal ligation and puncture (CLP) mouse model. CLP caused a time-dependent downregulation of renal vasopressin V-2 receptor and of AQP2 expression without alterations in plasma vasopressin levels. Renal activation of NF-kappa B in response to CLP was attenuated by PDTC pretreatment, which also attenuated the downregulation of V-2 receptor and AQP2 expression. Furthermore, a strong nuclear staining for the NF-kappa B p50 subunit throughout the whole kidney in response to CLP was observed. siRNA against NF-kappa B p50 attenuated the CLP-induced nuclear translocation of the p50 subunit and the CLP-induced downregulation of V-2 receptor and AQP2 expression. Additionally, PDTC and siRNA pretreatment inhibited the CLP-induced increase in renal TNF-alpha and IL-1 beta concentration and NOS-2 mRNA abundance. Moreover, PDTC and siRNA pretreatment ameliorated CLP-induced hypotension and ARF. Our findings suggest that NF-kappa B activation is of importance for the downregulation of AQP2 channel and vasopressin V-2 receptor expression during sepsis. In addition, our data indicate that NF-kappa B inhibition ameliorates sepsis-induced ARF.
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