La coordinación entre esfingolípidos y fosfoinosítidos es esencial para la diferenciación de las células tubulares renales

La diferenciación de las células epiteliales se produce por maduración de la membrana apical y desarrollo de cilio primario. Resultados previos de nuestro laboratorio demostraron que la hipertonicidad extracelular induce la diferenciación de las células MDCK, una línea celular derivada de túbulos colectores renales caninos, y que en este proceso son esenciales los esfingolípidos. Por otro lado, los fosfoinosítidos, otros lípidos bioactivos, son considerados determinantes de la polaridad apico - basal, dada su ubicación en dominios específicos de membrana en células epiteliales polarizadas: con PI(4,5)P2 localizado en el dominio apical y PI(3,4,5)P3 en el basolateral. Esta ubicación específica es la que determina el reclutamiento de complejos importantes de polaridad, como el Par3/Par6/aPKC.Fil: Pescio Lucila G.. Universidad de Buenos AiresFil: Romero, Daniela J.. Universidad de Buenos AiresFil: Santacreu, Bruno J.. Universidad de Buenos AiresFil: Francisco, María N..Fil: Favale, Nicolás O.. Universidad de Buenos AiresFil: Sterin-Speziale, Norma B.. Universidad de Buenos Aire

ApoSense: a novel technology for functional molecular imaging of cell death in models of acute renal tubular necrosis

Purpose: Acute renal tubular necrosis (ATN), a common cause of acute renal failure, is a dynamic, rapidly evolving clinical condition associated with apoptotic and necrotic tubular cell death. Its early identification is critical, but current detection methods relying upon clinical assessment, such as kidney biopsy and functional assays, are insufficient. We have developed a family of small molecule compounds, ApoSense, that is capable, upon systemic administration, of selectively targeting and accumulating within apoptotic/necrotic cells and is suitable for attachment of different markers for clinical imaging. The purpose of this study was to test the applicability of these molecules as a diagnostic imaging agent for the detection of renal tubular cell injury following renal ischemia. Methods: Using both fluorescent and radiolabeled derivatives of one of the ApoSense compounds, didansyl cystine, we evaluated cell death in three experimental, clinically relevant animal models of ATN: renal ischemia/reperfusion, radiocontrast-induced distal tubular necrosis, and cecal ligature and perforation-induced sepsis. Results: ApoSense showed high sensitivity and specificity in targeting injured renal tubular epithelial cells in vivo in all three models used. Uptake of ApoSense in the ischemic kidney was higher than in the non-ischemic one, and the specificity of ApoSense targeting was demonstrated by its localization to regions of apoptotic/necrotic cell death, detected morphologically and by TUNEL staining. Conclusion: ApoSense technology should have significant clinical utility for real-time, noninvasive detection of renal parenchymal damage of various types and evaluation of its distribution and magnitude; it may facilitate the assessment of efficacy of therapeutic interventions in a broad spectrum of disease states

Amino acid sequence, binding properties, and evolutionary relationships of the basic liver fatty acid-binding protein from the catfish Rhamdia sapo

Contains fulltext : 24657___.PDF (publisher's version ) (Open Access