Effect of ochratoxin A on cell survival and collagen homeostasis in human mesangial cells in primary culture.
Ochratoxin A (OTA) is a mycotoxin produced by several fungi growing on food source material. The main target of OTA is the kidney. So far, mainly cell lines of different origin have been used to study OTA toxicity. Yet all of them derived from tubule segments and therefore only limited information is available on glomerular effects of OTA. We exposed human mesangial cells in primary culture to OTA in nanomolar concentrations for up to 14 days. Necrotic and apoptotic cell death as well as fibrotic changes were studied. Protein content decreased only when unusual high OTA concentrations were used (1 microM). By contrast, an increase of caspase-3 activity or LDH release was observed after five days already at 10 nM OTA. A decrease of collagen I secretion was accompanied by a virtually unchanged collagen III and fibronectin secretion. Collagen IV secretion was slightly increased at low OTA concentrations (0.3-10 nM). We conclude that OTA has only a minor effect on human mesangial cells in primary culture. OTA did not influence collagen homeostasis substantially. Based on the data presented here, a risk of mesangial damage by OTA exposure is unlikely.
Schwerdt
Gerald
G
Julius-Bernstein-Institut für Physiologie, Martin-Luther-Universität Halle-Wittenberg, Magdeburger Strasse 6, D-06097 Halle (Saale), Germany. gerald.schwerdt@medizin.uni-halle.de
Holzinger
Hildegard
H
Königs
Maika
M
Humpf
Hans-Ulrich
HU
Gekle
Michael
M
D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D050527:Mesangial Cells / Q000187:drug effects* / Q000378:metabolism*; D009793:Ochratoxins / Q000633:toxicity*
D009793:Ochratoxins; C025589:ochratoxin A; D003094:Collagen; D007770:L-Lactate Dehydrogenase; D053148:Caspase 3