Your browser doesn't support javascript.
loading
Aprotinin prevents proteolytic epithelial sodium channel (ENaC) activation and volume retention in nephrotic syndrome.
Bohnert, Bernhard N; Menacher, Martina; Janessa, Andrea; Wörn, Matthias; Schork, Anja; Daiminger, Sophie; Kalbacher, Hubert; Häring, Hans-Ulrich; Daniel, Christoph; Amann, Kerstin; Sure, Florian; Bertog, Marko; Haerteis, Silke; Korbmacher, Christoph; Artunc, Ferruh.
Afiliação
  • Bohnert BN; Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry, University Hospital Tübingen, Tübingen, Germany; Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the Eberhards Karls University
  • Menacher M; Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry, University Hospital Tübingen, Tübingen, Germany.
  • Janessa A; Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry, University Hospital Tübingen, Tübingen, Germany.
  • Wörn M; Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry, University Hospital Tübingen, Tübingen, Germany.
  • Schork A; Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry, University Hospital Tübingen, Tübingen, Germany; Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the Eberhards Karls University
  • Daiminger S; Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry, University Hospital Tübingen, Tübingen, Germany.
  • Kalbacher H; Interfaculty Institute of Biochemistry, Eberhards Karls University of Tuebingen, Tübingen, Germany.
  • Häring HU; Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry, University Hospital Tübingen, Tübingen, Germany; Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the Eberhards Karls University
  • Daniel C; Institute of Pathology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany.
  • Amann K; Institute of Pathology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany.
  • Sure F; Institute of Cellular and Molecular Physiology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany.
  • Bertog M; Institute of Cellular and Molecular Physiology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany.
  • Haerteis S; Institute of Cellular and Molecular Physiology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany.
  • Korbmacher C; Institute of Cellular and Molecular Physiology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany.
  • Artunc F; Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry, University Hospital Tübingen, Tübingen, Germany; Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the Eberhards Karls University
Kidney Int ; 93(1): 159-172, 2018 01.
Article em En | MEDLINE | ID: mdl-29042083
ABSTRACT
Volume retention in nephrotic syndrome has been linked to activation of the epithelial sodium channel (ENaC) by proteolysis of its γ-subunit following urinary excretion of serine proteases such as plasmin. Here we tested whether pharmacological inhibition of urinary serine protease activity might protect from ENaC activation and volume retention in nephrotic syndrome. Urine from both nephrotic mice (induced by doxorubicin injection) and nephrotic patients exhibited high aprotinin-sensitive serine protease activity. Treatment of nephrotic mice with the serine protease inhibitor aprotinin by means of subcutaneous sustained-release pellets normalized urinary serine protease activity and prevented sodium retention, as did treatment with the ENaC inhibitor amiloride. In the kidney cortex from nephrotic mice, immunofluorescence revealed increased apical γ-ENaC staining, normalized by aprotinin treatment. In Xenopus laevis oocytes heterologously expressing murine ENaC, aprotinin had no direct inhibitory effect on channel activity but prevented proteolytic channel activation. Thus, our study shows that volume retention in experimental nephrotic syndrome is related to proteolytic ENaC activation by proteasuria and can be prevented by treatment with aprotinin. Hence, inhibition of urinary serine protease activity might become a therapeutic approach to treat patients with nephrotic-range proteinuria.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Equilíbrio Hidroeletrolítico / Inibidores de Serina Proteinase / Aprotinina / Edema / Canais Epiteliais de Sódio / Serina Proteases / Rim / Síndrome Nefrótica Tipo de estudo: Etiology_studies / Observational_studies Limite: Animals / Humans Idioma: En Revista: Kidney Int Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Equilíbrio Hidroeletrolítico / Inibidores de Serina Proteinase / Aprotinina / Edema / Canais Epiteliais de Sódio / Serina Proteases / Rim / Síndrome Nefrótica Tipo de estudo: Etiology_studies / Observational_studies Limite: Animals / Humans Idioma: En Revista: Kidney Int Ano de publicação: 2018 Tipo de documento: Article