Effect of Epidermal Growth Factor on Phosphate Uptake in Renal Proximal Tubule Cells: Involvement of PKC, MAPK, and cPLA 2

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Objective: The present study was conducted to examine the effect of epidermal growth factor (EGF) on Pi uptake and its related signal pathways in the primary cultured renal proximal tubule cells (PTCs). Results: EGF (50 ng/ml) inhibited Pi uptake, a typical marker of Na+/phosphate cotransporter, in a time- and dose-dependent manner. EGF-induced inhibition of Pi uptake was blocked by AG1478 (an EGF receptor antagonist), genistein or herbimycin A (tyrosine kinase inhibitors) and also blocked by mepacrine (a phospholipase A2 (PLA2) inhibitor) and AACOCF3 (a cPLA2 inhibitor). EGF increased [3H]-arachidonic acid (AA) release, which was also blocked by AG1478, genistein or herbimycin. Furthermore, EGF-induced inhibition of Pi uptake was blocked by indomethacin (a cyclooxygenase inhibitor) and econazole (a cytochrome P-450 epoxygenase inhibitor), but not by NDGA (a lipoxygenase inhibitor). On the other hand, EGF-induced inhibition of Pi uptake was blocked by staurosporine, H-7, or bisindolylmaleimide I (PKC inhibitors), PD 98059 (a p44/42 MAPK inhibitor), but not by SB 203580 (a p38 MAPK inhibitor). EGF-induced increase of [3H]-AA release was blocked by PKC inhibitors and a p44/42 mitogen-activated protein kinase (MAPK) inhibitor, but not by a p38 MAPK inhibitor. In addition, a PKC inhibitor blocked EGF-induced phosphorylation of p44/42 MAPK. Conclusion: EGF inhibits Pi uptake via PKC-p44/42 MAPK-cPLA2 pathway in the PTCs.

Related collections

Most cited references 14

Record: found
Abstract: found
Article: not found

Parathyroid hormone leads to the lysosomal degradation of the renal type II Na/Pi cotransporter.

I Ruf, Heini Murer, Susan Lederer … (1998)

We have studied the involvement of proteolytic pathways in the regulation of the Na/Pi cotransporter type II by parathyroid hormone (PTH) in opossum kidney cells. Inhibition of lysosomal degradation (by leupeptin, ammonium chloride, methylamine, chloroquine, L-methionine methyl ester) prevented the PTH-mediated degradation of the transporter, whereas inhibition of the proteasomal pathway (by lactacystin) did not. Moreover it was found (i) that whereas lysosomal inhibitors prevented the PTH-mediated degradation of the transporter they did not prevent the PTH-mediated inhibition of the Na/Pi cotransport and (ii) that treating opossum kidney cells with lysosomal inhibitors led to an increased expression of the transporter without any concomitant increase in the Na/Pi cotransport. Further analysis by subcellular fractionation and morphological techniques showed (i) that the Na/Pi cotransporter is constitutively transported to and degraded within late endosomes/lysosomes and (ii) that PTH leads to the increased degradation of the transporter in late endosomes/lysosomes.

0 comments Cited 25 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Characterization of primary rabbit kidney cultures that express proximal tubule functions in a hormonally defined medium

N Alavi, D. M. Livingston, S Hiller … (1982)

Primary cultures of rabbit-kidney epithelial cells derived from purified proximal tubules were maintained without fibroblast overgrowth in a hormone-supplemented serum-free medium (Medium RK-1). A hormone- deletion study indicated that the primary cultures derived from purified rabbit proximal tubules required all of the three supplements in Medium RK-1 (insulin, transferrin, and hydrocortisone) for optimal growth but did not grow in response to EGF and T3. In contrast, the epithelial cells in primary cultures derived from an unpurified preparation of rabbit kidney tubules and glomeruli grew in response to EGF and T3, as well as insulin, transferrin, and hydrocortisone. These observations suggest that kidney epithelial cells derived from different segments of the nephron grow differently in response to hormones and growth factors. Differentiated functions of the primary cultures derived from proximal tubules were examined. Multicellular domes were observed, indicative of transepithelial solute transport by the monolayers. The proximal tubule cultures also accumulated alpha- methylglucoside (alpha-MG) against a concentration gradient. However, little or no alpha-MG accumulation was observed in the absence of Na+. Metabolic inhibitor studies also indicated that alpha-MG uptake by the primaries is an energy-dependent process, and depends upon the activity of the Na+/K+ ATPase. Phlorizin at 0.1 mM significantly inhibited 1 mM alpha-MG uptake whereas 0.1 mM phloretin did not have a significant inhibitory effect. Similar observations have been made concerning the Na+-dependent sugar-transport system located on the lumenal side of the proximal tubule, whereas the Na+-independent sugar transporter on the peritubular side is more sensitive to inhibition by phloretin than phlorizin. The cultures also exhibited PTH-sensitive cyclic AMP synthesis and brush-border enzymes typical of proximal cells. However, the activities of the enzymes leucine aminopeptidase, alkaline phosphatase, and gamma-glutamyl-transpeptidase were lower in the cultures than in purified proximal-tubule preparations from which they are derived.

0 comments Cited 22 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Regulation of Na/Pi transporter in the proximal tubule.

Heini Murer, Nati Hernando, Ian Forster … (2002)

The physiological tuning and pathophysiological alterations of renal proximal reabsorption of inorganic phosphate can be ascribed to the net amount of the Na/Pi-cotransporter NaPi-IIa localized in the brush border membrane. The net amount of NaPi-IIa appears to be the result of an endocytotic rate regulated by a complex network of different protein kinases. New approaches demonstrated that NaPi-IIa is part of heteromeric protein complexes, organized by PDZ (postsynaptic protein PSD95, Drosophila junction protein Disc-large, tight junction protein ZO-1) proteins. Such complexes are thought to play important roles in the apical positioning and regulated endocytosis of NaPi-IIa and therefore such interactions have to be considered when explaining proximal phosphate ion reabsorption.

0 comments Cited 19 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (publisher-id): KBR

Journal ID (nlm-ta): Kidney Blood Press Res

Journal ID (doi): 10.1159/issn.1420-4096

Title: Kidney and Blood Pressure Research

Publisher: S. Karger AG

ISSN (Print): 1420-4096

ISSN (Electronic): 1423-0143

Publication date Subscription-year: 2003

Publication date (Print): 2003

Publication date (Electronic): 19 November 2003

Volume: 26

Issue: 5-6

Pages: 315-324

Affiliations

^aDepartment of Veterinary Physiology, College of Veterinary Medicine, Hormone Research Center, Chonnam National University, Gwangju, and ^bCollege of Veterinary Medicine, Chonbuk National University, Jeonju,Korea

Article

Publisher ID: 73937 Other ID: Kidney Blood Press Res 2003;26:315–324

DOI: 10.1159/000073937

PubMed ID: 14610335

SO-VID: 9db636c6-5896-4a5c-a803-6356601616a9

License:

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.

History

Date received : 05 May 2003

Page count

Figures: 10, Tables: 1, References: 53, Pages: 10

Comments

Comment on this article

scite_

Cited by 1

Regulation of Taurocholate Transport in Freshly Isolated Proximal Tubular Cells of the Rat Kidney by Protein Kinases
Authors: Jan Schlattjan, Susanne Benger, Andreas Herrler …

See all cited by

Call for Papers: Green Renal Replacement Therapy: Caring for the Environment

Submit here before July 31, 2024

Effect of Epidermal Growth Factor on Phosphate Uptake in Renal Proximal Tubule Cells: Involvement of PKC, MAPK, and cPLA ₂

Read this article at

Abstract

Related collections

Karger: Nephrology

Most cited references 14

Parathyroid hormone leads to the lysosomal degradation of the renal type II Na/Pi cotransporter.

Characterization of primary rabbit kidney cultures that express proximal tubule functions in a hormonally defined medium

Regulation of Na/Pi transporter in the proximal tubule.

Author and article information

Journal

Affiliations

Article

History

Page count

Categories

Comments

Comment on this article

Similar content 240

Cited by 1