The nephrotoxin ochratoxin A induces apoptosis in cultured human proximal tubule cells

Citation
G. Schwerdt et al., The nephrotoxin ochratoxin A induces apoptosis in cultured human proximal tubule cells, CELL BIOL T, 15(6), 1999, pp. 405-415
Citations number
35
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
CELL BIOLOGY AND TOXICOLOGY
ISSN journal
0742-2091 → ACNP
Volume
15
Issue
6
Year of publication
1999
Pages
405 - 415
Database
ISI
SICI code
0742-2091(1999)15:6<405:TNOAIA>2.0.ZU;2-9
Abstract
To test the apoptotic potential of the nephrotoxic mycotoxin ochratoxin A ( OTA), we exposed human proximal tubule-derived cells (IHKE cells) for vario us times to OTA concentrations close to those occurring during dietary expo sure (from 2 to 100 nmol/L) and investigated caspase 3 activation, chromati n condensation, and DNA fragmentation. OTA induced a time- and concentratio n-dependent activation of caspase 3: concentrations as low as 5 nmol/L OTA caused a slight but significant increase in caspase 3 activity after 7 days of OTA exposure. Exposure to 10 nmol/L OTA for 72 or 24 h led to a signifi cantly increased activity of caspase 3 in human proximal tubule-derived cel ls. Radical scavengers such as N-acetylcysteine had no effect on OTA-induce d caspase 3 activation. Chelation of intracellular calcium with 1,2-bis(2-a minophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis (acetoxymethylester) (BAPTA-AM) also showed no effect. Exposure to 30 nmol/L or more OTA led to DNA fragmentation and chromatin condensation in IHKE cells. Cultured renal epithelial MDCK-C7 and MDCK-C11 or OK cells also showed increased caspase 3 activity after OTA exposure. We conclude that exposure to low OTA concent rations can lead to direct or indirect caspase 3 activation and subsequentl y to apoptosis in cultured human proximal tubule cells and in other renal e pithelial cell lines of different origins.