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      Defective Proximal Tubule Lysosomal Acidification by Bence Jones Proteins

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          Abstract

          Proximal tubule handling of two human Bence Jones proteins (neutral and acidic BJP) was evaluated using protein A-gold labelling. After 30 min of acute light-chain infusion into 6 rats (alone or in combination with dinitrophenyl-aminopropyl-methylamine [DAMP]), kidney biopsies were processed for immunoelectron microscopy. Antibodies directed at monoclonal lambda light chains, mannose-6-phosphate cation-independent receptor (MPR) and DAMP were used.Labelling density (number of pA-gold particles/µm<sup>2</sup>), expressed as median (25–75 percentiles), differed (p < 0.05) between the two BJP, being 94.5 (32.9–212.5) vs. 19.4 (3.7–45.6) pA-gold/µm<sup>2</sup> in endocytic vacuoles, and 297.3 (207.1–382.1) vs. 83.2 (16.6–197.0) pA-gold/µm<sup>2</sup> in non-vacuolar electrondense endosome-lysosome structures. Labelling density for MPR was 47.7 (22.2–84.6) vs. 4.0 (2.7–6.3) pA-gold/µm<sup>2</sup>. The area of MPR-labelled structures was also different, i.e.: 0.2 (0.1–0.4) vs. 0.9 (0.5–1.8) µm<sup>2</sup>. The endosome-lysosome pH distribution range differed significantly: 6.8 (6.4–7.0) vs. 6.3 (5.8–7.0). There was a significant accumulation of neutral BJP in endocytic structures, an acidification deficit of pre-lysosomes/lysosomes and MPR retention, suggestive of defective receptor recycling with this BJP. Interference with the physiological process of lysosomal acidification may be an important mechanism of higher nephrotoxicity in some BJP.

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          Most cited references 3

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          Méthode permettant l'étude conjuguée des propriétés électrophorétiques et immunochimiques d'un mélange de protéines. Application au sérum sanguin

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            Membrane traffic in endocytosis: insights from cell-free assays.

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              Detection of Bence-Jones protein by isoelectricfocussing of unconcentrated urine followed by nitrocellulose blotting and immunoperoxidase staining

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                Author and article information

                Journal
                EXN
                Nephron Exp Nephrol
                10.1159/issn.1660-2129
                Cardiorenal Medicine
                S. Karger AG
                1660-2129
                1998
                December 1998
                06 November 1998
                : 6
                : 6
                : 514-521
                Affiliations
                a Laboratório de Fisiopatologia Renal da Faculdade de Medicina, b Laboratório de Patologia Molecular da Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
                Article
                20566 Exp Nephrol 1998;6:514–521
                10.1159/000020566
                © 1998 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 4, Tables: 2, References: 40, Pages: 8
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/20566
                Categories
                Original Paper

                Cardiovascular Medicine, Nephrology

                Endo-lysosomal system, Multiple myeloma, Bence Jones proteins

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