Ochratoxin A at nanomolar concentrations: a signal modulator in renal cells.
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.
Gekle
Michael
M
Physiologisches Institut der Universität Würzburg, Würzburg, Germany. michael.gekle@uni-wuerzburg.de
Sauvant
Christoph
C
Schwerdt
Gerald
G
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D004734:Energy Metabolism; D004781:Environmental Exposure; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D020928:Mitogen-Activated Protein Kinases; D009793:Ochratoxins / Q000032:analysis* / Q000494:pharmacology* / Q000633:toxicity; D012307:Risk Factors; D015398:Signal Transduction / Q000187:drug effects*
D009793:Ochratoxins; C025589:ochratoxin A; D020928:Mitogen-Activated Protein Kinases; D002118:Calcium