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Ochratoxin A at nanomolar concentrations: a signal modulator in renal cells
Michael Gekle1, Christoph Sauvant, Gerald Schwerdt
1Physiologisches Institut der Universität Würzburg, Würzburg, Germany. michael.gekle@uni-wuerzburg.de
Abstract:
Ochratoxin A (OTA) is a ubiquitous fungal metabolite with nephrotoxic, carcinogenic, and apoptotic potential. Toxicokinetics make the kidney the primary target organ for OTA. Due to its widespread occurrence in improperly stored foodstuff the complete and safe avoidance of OTA for humans is impossible. There are several reports showing a significant correlation between OTA exposure and certain forms of nephropathies. At nanomolar concentrations OTA leads to specific changes of function and phenotype in renal cells. The toxin interacts with certain cellular "key-molecules" (e. g., mitogen-activated protein (MAP) kinases, Ca2+), thereby disturbing cellular signalling and regulation events as well as mitochondrial function. Moreover, OTA has the ability to modulate physiological signals (e. g., angiotensin II or TNFalpha) and thereby influences cell function and cell growth and may even stable re-program the cells (e. g., altered distribution of chromosomes). This review concentrates on the effects of OTA in the nanomolar range and its interactions with cellular signalling networks in different renal cells proposing OTA to act as a signal modulator.
Insights
Ochratoxin A (OTA), a common food contaminant, targets the kidney even at low nanomolar concentrations. This fungal toxin disrupts cellular signaling pathways and mitochondrial function in renal cells, acting as a potent signal modulator.
Area of Science:
- Toxicology
- Cell Biology
- Nephrology
Background:
- Ochratoxin A (OTA) is a widespread fungal toxin found in food.
- OTA is known for its nephrotoxic, carcinogenic, and apoptotic effects.
- The kidney is the primary target organ for OTA due to its toxicokinetics.
Purpose of the Study:
- To review the effects of Ochratoxin A (OTA) at nanomolar concentrations.
- To investigate OTA's interactions with cellular signaling networks in renal cells.
- To propose OTA as a signal modulator in the kidney.
Main Methods:
- Literature review focusing on OTA's effects in the nanomolar range.
- Analysis of studies detailing OTA's interaction with cellular key molecules (e.g., MAP kinases, Ca2+).
- Examination of OTA's influence on cellular signaling and mitochondrial function.
Main Results:
- OTA at nanomolar concentrations induces specific functional and phenotypic changes in renal cells.
- OTA interferes with cellular signaling pathways, including MAP kinases and Ca2+ signaling.
- OTA disrupts mitochondrial function and modulates physiological signals like angiotensin II and TNFalpha.
Conclusions:
- Ochratoxin A acts as a signal modulator in renal cells, even at low concentrations.
- OTA's interaction with cellular signaling networks can lead to altered cell function, growth, and potentially stable cellular reprogramming.
- Complete avoidance of OTA is impossible, highlighting the importance of understanding its renal effects.
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