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Published on: June 29, 2011

Ochratoxin A induces JNK activation and apoptosis in MDCK-C7 cells at nanomolar concentrations

M Gekle1, G Schwerdt, R Freudinger

  • 1Physiologisches Institut, Würzburg, Germany. michael.gekle@mail.uni-wuerzberg.de

The Journal of Pharmacology and Experimental Therapeutics
|June 28, 2000
PubMed

Insights

Ochratoxin A (OTA) triggers c-jun amino-terminal-kinase (JNK) and apoptosis in specific kidney cells. This cell-specific interaction with mitogen-activated protein kinases (MAPK) explains some OTA-induced kidney damage and teratogenic effects.

Area of Science:

  • Toxicology
  • Cell Biology
  • Molecular Biology

Background:

  • Ochratoxin A (OTA) is a fungal metabolite linked to kidney disease, cancer, and birth defects.
  • Previous studies showed OTA activates extracellular signal-regulated kinases 1 and 2 (ERK1/2) in a cell-specific manner.
  • The precise molecular mechanisms underlying OTA's toxicity remain under investigation.

Purpose of the Study:

  • To investigate the effect of nanomolar Ochratoxin A (OTA) on c-jun amino-terminal-kinase (JNK) activation in renal epithelial cells.
  • To determine if OTA induces apoptosis in a cell-specific manner.
  • To explore the role of the JNK pathway in OTA-induced cellular effects.

Main Methods:

  • Utilized Madin-Darby canine kidney (MDCK) cell clones (C7 and C11) with differing sensitivities to OTA.
  • Assessed JNK activation using kinase assays and Western blotting.
  • Quantified apoptosis through DNA fragmentation, DNA laddering, and caspase activation assays.

Main Results:

  • Nanomolar OTA concentrations activated JNK specifically in MDCK-C7 cells, not MDCK-C11 cells.
  • OTA potentiated JNK activation induced by tumor necrosis factor-alpha (TNF-α).
  • OTA induced apoptosis in MDCK-C7 cells, an effect also potentiated by TNF-α.

Conclusions:

  • Ochratoxin A exhibits cell-type-specific interactions with mitogen-activated protein kinase (MAPK) family members, including JNK.
  • JNK pathway activation and subsequent apoptosis in specific renal cells contribute to OTA's nephrotoxic and teratogenic potential.
  • These findings elucidate key molecular pathways involved in OTA toxicity at non-acutely toxic concentrations.

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