Effect of the mycotoxin, ochratoxin A, on hormone-stimulated ion transport in a cultured cell model of the renal principal cell

Abstract

The mycotoxin ochratoxin A (OTA) is a common contaminant of many foodstuffs and, consequently, is present in a large proportion of tested populations of humans and commercial animals. The predominant effects of OTA are manifested in the kidney where the severity varies from salt wasting to renal carcinoma formation in a concentration-dependent fashion. The MDCK-C7 renal cell culture model responds to various hormones known to regulate electrolyte and fluid balance and was used as a model to study the chronic effects of an acute exposure to low dose OTA. The natriferic hormones aldosterone and insulinlike growth factor 1 (IGF1) both stimulate Na + flux in a reabsorptive direction via activation of the epithelial Na + channel (ENaC). In contrast, anti-diuretic hormone (ADH) stimulates three separate and temporally distinct ion transport responses, one of which is Na + reabsorption. Treatment of MDCK-C7 cells with OTA (100 nM) for 48 h selectively and irreversibly inhibits hormone-stimulated Na + reabsorption via ENaC. This effect was retained for 48 cell passages after the removal of the toxin and mimics the OTA-induced salt-wasting that has been documented in clinical studies. These studies indicate that the effect of the toxin is genomic and therefore, likely to be long lasting in exposed animals and humans.

Distinct domain-dependent effect of syntaxin1A on amiloride-sensitive sodium channel (ENaC) currents in HT-29 colonic epithelial cells

“…In order to explore the effect of syntaxin1A on ENaC in HT-29 cells, we over-expressed syntaxin1A and its major cytosolic domains and recorded amiloride-sensitive currents (Fig 1 ). We recorded considerable currents (2-3 μA/cm 2 ) that could be stimulated by aldosterone (>2.5 fold) (not shown) as reported in other cell systems like A6 39 , 40 , MDCK 41 and mpkCCD c14 42 . Over-expression of syntaxin1A produced from 50% to 100% stimulation of amiloride-sensitive currents, while the expression of H3 domain showed the inhibition as reported in the Xenopus oocyte system 16 .…”

Balkan endemic nephropathy: Role of ochratoxins A through biomarkers

“…For this individual, regular and continuous OTA intake equivalent to 1.2-2.2 ng/kg bw/ day leads to a relatively high OTA blood steady-state concentration (1.46 lg/L) and a low OTA elimination. This could be explained by the alteration in electrolyte transport (Na+/K+) by a low dose of OTA [30] leading to a reduction of OTA urinary excretion and thus an increase of OTA blood concentration. Due to the equilibrium between bound OTA and free OTA (in tissue and blood), the daily intake of individual BI 06, BI 12 and GP 04 is not sufficient to saturate all protein binding sites, and thus the majority of OTA is found as free OTA in blood.…”

Novel Perspective on Mechanism in Muscle Growth Inhibited by Ochratoxin A Associated with Ferroptosis: Model of Juvenile Grass Carp (Ctenopharyngodon idella) In Vivo and In Vitro Trials

“…34 Although there is no relevant research on the effect of OTA on the MRFs family, studies on MDCK-C7 cells have shown that OTA treatment inhibits the expression of insulinlike growth factor 1 (IGF1). 35 In IGF1 knockout mice, Myf6 and MyoG mRNA expressions were significantly reduced. 36 AKT, as a key signaling molecule downstream of IGF1, plays a crucial role in myoblast fusion.…”

“…So far, only one study has shown that OTA reduces the expression of MyHC in chicken kidneys . Although there is no relevant research on the effect of OTA on the MRFs family, studies on MDCK-C7 cells have shown that OTA treatment inhibits the expression of insulin-like growth factor 1 (IGF1) . In IGF1 knockout mice, Myf6 and MyoG mRNA expressions were significantly reduced .…”