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Titolo:
Inhibition of Na+/H+ exchange suppresses albumin-induced NF-kappa B activation
Autore:
Drumm, K; Gassner, B; Silbernagl, S; Gekle, M;
Indirizzi:
Univ Wurzburg, Inst Physiol, D-97070 Wurzburg, Germany Univ Wurzburg Wurzburg Germany D-97070 hysiol, D-97070 Wurzburg, Germany
Titolo Testata:
NIEREN-UND HOCHDRUCKKRANKHEITEN
fascicolo: 4, volume: 30, anno: 2001,
pagine: 141 - 149
SICI:
0300-5224(200104)30:4<141:IONESA>2.0.ZU;2-V
Fonte:
ISI
Lingua:
GER
Soggetto:
RENAL PROXIMAL TUBULE; THICK ASCENDING LIMB; EPITHELIAL-CELLS; APICAL MEMBRANE; ENDOCYTOSIS; NHE3; ISOFORM; LOCALIZATION; PROTEINURIA; EXPRESSION;
Keywords:
albumin; NF-kappa B; Na+/H+ exchange; endocytosis; renal proximal tubular cells;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Drumm, K Univ Wurzburg, Inst Physiol, Rontgenring 9, D-97070 Wurzburg, Germany Univ Wurzburg Rontgenring 9 Wurzburg Germany D-97070 rg, Germany
Citazione:
K. Drumm et al., "Inhibition of Na+/H+ exchange suppresses albumin-induced NF-kappa B activation", NIEREN HOCH, 30(4), 2001, pp. 141-149

Abstract

Several studies support a role of filtered albumin in the pathogenesis of renal interstitial inflammation and fibrosis. At least, parts of these effects are mediated by the nuclear factor kappaB (NF-kappaB). Na+-H+ exchanger(NHE) isoform 3 supports receptor-mediated endocytosis of albumin in renalproximal tubular cells by a yet not completely understood mechanism. We tested the hypothesis that pharmacological inhibition of NHE reduces albumin-induced NF-kappaB activation using established proximal tubular cell lines. We exposed opossum (OK) and porcine (LLC-PK1) renal proximal tubular cellsto bovine serum albumin (BSA). To inhibit NHE, 5-(N-ethyl-N-isopropyl)-amiloride (EIPA) was used. Albumin endocytosis was determined via FITC-BSA uptake studies, and NF-kappaB-specific DNA-binding activity in BSA-exposed cells was detected by electromobility gel shift assays (EMSAs). EIPA reduced albumin uptake in OK and LLC-PK1 cells, with IC50 values corresponding to NHE-3 inhibition. The albumin-induced increase in NF-kappaB DNA-binding activity was prevented by EIPA in OK and LLC-PK1 cells. NF-kappaB activation by the phorbol eater PMA was not affected by EIPA. We suggest that NHE-dependent albumin endocytosis induces an increase in NF-kappaB-specific protein activity in renal proximal tubular cells in vitro, which is impaired by EIPA. Thus inhibition of albumin uptake in proximal tubular cells might be a therapeutical strategy to prevent albumin-induced NF-kappaB activation and albumin-induced inflammatory or fibrotic renal pathomechanisms in vivo.

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Documento generato il 20/01/20 alle ore 04:50:25