| Item type: | Article | ||||
|---|---|---|---|---|---|
| Journal or Publication Title: | American Journal of Physiology-Renal Physiology | ||||
| Publisher: | AMER PHYSIOLOGICAL SOC | ||||
| Place of Publication: | BETHESDA | ||||
| Volume: | 298 | ||||
| Number of Issue or Book Chapter: | 1 | ||||
| Page Range: | F196-F204 | ||||
| Date: | 2010 | ||||
| Institutions: | Medicine > Lehrstuhl für Anästhesiologie Biology, Preclinical Medicine > Institut für Physiologie Chemistry and Pharmacy > Institute of Pharmacy > Pharmacology and Toxicology (Prof. Schlossmann, formerly Prof. Seifert) | ||||
| Identification Number: |
| ||||
| 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 Decimal Classification: | 500 Science > 540 Chemistry & allied sciences 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine 600 Technology > 615 Pharmacy | ||||
| Status: | Published | ||||
| Refereed: | Yes, this version has been refereed | ||||
| Created at the University of Regensburg: | Yes | ||||
| Item ID: | 66481 |
Web of ScienceAbstract
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 ...
Abstract
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.
Metadata last modified: 19 Dec 2024 11:44
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