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Table of Contents
Vol. 15, No. 1-4, 2005
Issue release date: January 2005
Section title: Original Paper
Cell Physiol Biochem 2005;15:125–134
(DOI:10.1159/000083660)

The Nephrotoxin Ochratoxin A Induces Key Parameters of Chronic Interstitial Nephropathy in Renal Proximal Tubular Cells

Sauvant C. · Holzinger H. · Gekle M.
Physiologisches Institut; Universitaet Wuerzburg
email Corresponding Author

Christoph Sauvant; Dr. rer. nat.

Physiologisches Institut, Universität Würzburg

Röntgenring 9, 97070 Würzburg (Germany)

Tel. +49 931 31-2724, Fax: +49 931 31-2741

E-Mail christoph.sauvant@mail.uni-wuerzburg.de

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Abstract

Ochratoxin A (OTA) is a nephrotoxic and cancerogenic mycotoxin. There is epidemiological evidence that OTA exposition leads to cortical interstitial nephropathies in humans. However, virtually no data are available investigating the effect of OTA on renal cortical cells with respect to induction of nephropathy. Thus, we investigated whether OTA is able to induce changes of cellular properties potentially leading to interstitial nephropathy, using proximal tubular cell lines (OK, NRK-52E). OTA decreased cell number and cell protein time and dose dependently. Accordingly we investigated the effect of 100 nM or 1000 nM OTA. The decline of cell number after OTA exposure is due to necrosis and apoptosis, as measured by LDH release or DNA ladder formation and caspase-3 activation, respectively. OTA incubation of proximal tubular cells also resulted in a loss of epithelial tightness as determined by diffusion of FITC labeled inulin. Inflammation, fibrosis and epithelial-to-mesenchymal transition are described in chronic interstitial renal disease. Therefore, we also investigated the effect of OTA on NFκB activity, collagen secretion and generation of α smooth muscle actin. OTA alone was sufficient to induce the latter parameters in proximal tubular cells. Finally, OTA is a nephrotoxcic substance and elevated activity of mitogen activated protein kinases (MAPK) is described in nephropathies. As we investigated the effect of OTA on activity of ERK, JNK and p38 by ELISA, we found that OTA activates the MAPK measured dose dependently. In summary, OTA induced phenomena typical for chronic interstitial nephropathy, like loss of cells and epithelial tightness, necrosis and apoptosis as well as markers of inflammation, fibrosis and epithelial-to-mesenchymal transition in proximal tubular cells. Thus, we could show for the first time that OTA is able to induce key parameters of nephropathy in proximal tubular cells in culture. Moreover OTA interacts with MAPK and thus may exert its specific toxic actions.

© 2005 S. Karger AG, Basel


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Accepted: August 10, 2004
Published online: January 13, 2005
Issue release date: January 2005

Number of Print Pages: 10
Number of Figures: 0
Number of Tables: 0

ISSN: 1015-8987 (Print)
eISSN: 1421-9778 (Online)

For additional information: http://www.karger.com/CPB


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