Hoecherl, Klaus and Schmidt, Christoph and Kurt, Birguel and Bucher, Michael (2010) Inhibition of NF-kappa B ameliorates sepsis-induced downregulation of aquaporin-2/V-2 receptor expression and acute renal failure in vivo. AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 298 (1). F196-F204. ISSN 1931-857X,
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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.
| Item Type: | Article |
|---|---|
| Uncontrolled 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 |
| Subjects: | 500 Science > 540 Chemistry & allied sciences 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine 600 Technology > 615 Pharmacy |
| Divisions: | Medicine > Lehrstuhl für Anästhesiologie Biology, Preclinical Medicine > Institut für Physiologie Chemistry and Pharmacy > Institute of Pharmacy > Pharmacology and Toxicology (Prof. Schlossmann, formerly Prof. Seifert) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Aug 2020 05:32 |
| Last Modified: | 12 Aug 2020 05:32 |
| URI: | https://pred.uni-regensburg.de/id/eprint/25336 |
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