C 3-Professur für Physiologie (Gekle)
Röntgenring 9, 97070 Würzburg
Other participating persons and organisations:
Research foci (and basic equipment-based research projects):
Ochratoxin A (OTA) is a ubiquitous fungal metabolite with nephrotoxic, carcinogenic and apoptotic potential. Toxokinetics 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. Up to date the contribution OTA to the pathogenesis of human renal diseases has not been conclusively proven.. However, there are reports showing a significant correlation between OTA exposure and certain forms of nephropathies. At toxicological relevant concentrations OTA leads to specific changes of function and phenotype in renal cells. The toxin interacts with certain cellular "key-molecules" (e.g. MAP kinases), 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 TNFa) and thereby influences cell function and cell growth and may even stable re-program the cells (e.g. altered distribution of chromosomes).
BENESIC, A., S. MILDENBERGER AND M. GEKLE. Nephritogenic ochratoxin A interferes with hormonal signalling in immortalised human kidney epithelial cells. Eur. J. Physiol. (Pflügers Arch.) 439:278-287, 2000.
SCHWERDT, G., R. FREUDINGER, S. MILDENBEGER, S. SILBERNAGL AND M. GEKLE. The nephrotoxin ochratoxin A induces apoptosis in cultured human proximal tubule cells. Cell. Biol. Toxicol. 15:405-415, 1999.
GEKLE, M., G. SCHWERDT, R. FREUDINGER, S. MILDENBERGER, D. WILFLINGSEDER, V. POLLACK, M. DANDER AND H. SCHRAMEK. Ochratoxin A induces JNK activation and apoptosis in MDCK-C7 cells at nanomolar concentrations. J. Pharmacol. Exp. Ther. 293:837-844, 2000.
EDER, S., A. BENESIC, R. FREUDINGER, J. ENGERT, G. SCHWERDT, K. DRUMM AND M. GEKLE. Nephritogenic ochratoxin A interferes with mitochondrial function and pH-homeostasis of immortalized human kidney epithelial cells. Eur. J. Physiol. (Pflügers Arch.) 440:521-529, 2000.
SCHWERDT, G., R. FREUDINGER, S. SILBERNAGL AND M. GEKLE. Ochratoxin A-binding proteins in rat organs and plasma and in different cell lines of the kindey. Toxicology 135: 1-10, 1999.