NDLI: Characterization of ochratoxin A-induced apoptosis in primary rat hepatocytes

Content Provider	Springer Nature Link
Author	Chopra, Martin Link, Pascal Michels, Christine Schrenk, Dieter
Copyright Year	2009
Abstract	The main target organ of the mycotoxin ochratoxin A (OTA) in mammals is the kidney but OTA has also been shown to be hepatotoxic in rats and to induce tumors in mouse liver. Even at very low concentrations, OTA causes perturbations of cellular signaling pathways as well as enhanced apoptosis. OTA has been extensively studied in kidney cell systems. Since this substance also affects liver health, we focused our work on apoptosis-related events induced by OTA in primary rat hepatocytes. We performed pathway-specific polymerase chain reaction arrays to assess the expression of genes involved in apoptosis. Treatment with 1 µM OTA for 24 h caused marked changes in apoptosis-related gene expression. Genes as apaf1, bad, caspase 7, polb (DNA polymerase beta, performs base excision repair), and p53, which are marker genes for DNA damage, were upregulated. FAS and faslg were also markedly induced by treatment with OTA. Treatment of hepatocytes with OTA led to a concentration-dependent inhibition of protein biosynthesis. Apoptosis-inducing factor was released from mitochondria following OTA treatment; the mycotoxin induced the activity of caspases 8, 9, and 3/7 and caused chromatin condensation and fragmentation. Caspase inhibition led to a significant but not complete reduction of OTA-induced apoptosis. Our data suggest that not only OTA leads to p53-dependent apoptosis in rat hepatocytes but it also hints to other mechanisms, independent of caspase activation or protein biosynthesis, being involved.
Starting Page	239
Ending Page	254
Page Count	16
File Format	PDF
ISSN	07422091
Journal	Cell Biology and Toxicology
Volume Number	26
Issue Number	3
e-ISSN	15736822
Language	English
Publisher	Springer Netherlands
Publisher Date	2009-06-27
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	Apoptosis Caspases Hepatocytes Mycotoxins Ochratoxin A Biochemistry Pharmacology/Toxicology Cell Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Health, Toxicology and Mutagenesis Toxicology

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