|
Tang CY, Chen YW, Jow GM, Chou CJ, Jeng CJ.
Chem Res Toxicol. 2005 May;18(5):825-33.
Beauvericin activates Ca2+-activated Cl- currents and induces cell deaths in
Xenopus oocytes via influx of extracellular Ca2+.
Department of Physiology, College of Medicine, National Taiwan University,
Taipei, Taiwan.
Beauvericin is a mycotoxin that infects a wide variety of cereal grains. The
toxicological importance of beauvericin is implicated by its cytotoxicity in
animal and human cells, which has been suggested to result from an increase in
intracellular Ca(2+) concentration ([Ca(2+)](i)). Despite the fact that
beauvericin may activate extracellular Ca(2+) influx, beauvericin-induced cell
deaths has been suggested to be exclusively due to Ca(2+) release from internal
Ca(2+) stores. We endeavored to elucidate the mechanism of beauvericin-induced
[Ca(2+)](i) increase by studying the effects of beauvericin in Xenopus oocytes.
By applying a -140-mV prepulse prior to a series of test pulses, we found that
beauvericin induced small inward currents at -140 mV, followed by outwardly
rectifying currents that displayed an apparent reversal potential close to the
expected equilibrium potential of Cl(-). Both the inward and outward currents
induced by beauvericin were blocked by niflumic acid, a specific blocker for
Ca(2+)-activated Cl(-) currents (I(Cl,Ca)). Removal of extracellular Ca(2+), as
well as perfusion of lanthanide, abrogated beauvericin-induced currents.
Beauvericin also displayed prominent cytotoxic effects in Xenopus oocytes in a
dose-dependent manner. In the absence of extracellular Ca(2+), cytotoxicity-induced
by 10 and 30 microM, but not 50 microM, of beauvericin was significantly
diminished. Our results are consistent with the idea that beauvericin induces
extracellular Ca(2+) influx, which in turn activates I(Cl,Ca) and contributes to
beauvericin-induced cell deaths in Xenopus oocytes
PMID: 15892576
|
