IFIBIO HOUSSAY   25014
INSTITUTO DE FISIOLOGIA Y BIOFISICA BERNARDO HOUSSAY
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Effect of Subtilase cytotoxin on renal protein handling (RPH)
Autor/es:
SEYAHIAN, E. A; OLTRA, G; MELENDI, S; PATON, J. C; PATON, A. W; LAGO, N; CASTRO PARODI, M; DAMIANO, A. E; OCHOA, F; ZOTTA, E
Lugar:
Boston
Reunión:
Congreso; 9th Triennial International Symposium on Shiga Toxin Producing Escherichia coli Infections; 2015
Resumen:
Introduction: In Argentina, Hemolytic Uremic Syndrome (HUS) constitutes the leading cause of acute renal failure in children. Renal damage has been associated with Shiga toxin (Stx) produced by E. coli O157:H7 and other STEC serotypes. It was recently, described that E. coli O113:H21 produces an additional cytotoxin: Subtilase cytotoxin (SubAB).In previous works we have described Stx effects on RPH at glomerular and tubular levels.Taking into account that a role for SubAB in HUS pathology has not been clearly established,the aim of our work was to study what happened with RPH.Methods: Male Sprague Dawley rats, (200 g) were inoculated intraperitoneally with 15 μg/200 g BW of purified SubAB. We performed functional, histological, immunohistochemical (IHC) and molecular studies at 48 hs and 20 days.Results and Discussion: Rats presented microalbuminuria only at 20 days. We described at 48 hs tubular and glomerular necrosis. Focal and Segmental Glomerulosclerosis and podocyte villous transformation by Electron Microscopy (EM) at 20 days were observed. We evaluated Synaptopodyn podocyte expression and the protein tubular endocytosis mechanism. Megalin expression was diminished at both times by Immunofluorescence, but mRNA increased at 48 hs and markedly decreased at 20 days. NHE-3 protein expression was diminished at 48 hs and returned to normal at 20 days. SubAB produced alterations in RPH without effects on survival. Implications: Not much is known about SubAB and its role in human pathology. As kidneys constitute target organs of HUS, and chronic kidney disease is a feared outcome, the clarification of the contribution of SubAB could be important in the prognosis and treatment of patients.