Beauvericin activates Ca2+-activated Cl- currents and induces cell deaths in Xenopus oocytes via influx of extracellular Ca2+.
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.
Tang
Chih-Yung
CY
Department of Physiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Chen
Yi-Wen
YW
Jow
Guey-Mei
GM
Chou
Cheng-Jen
CJ
Jeng
Chung-Jiuan
CJ
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects* / Q000502:physiology; D018118:Chloride Channels / Q000187:drug effects* / Q000502:physiology; D002712:Chlorides / Q000378:metabolism; D047630:Depsipeptides / Q000494:pharmacology*; D004553:Electric Conductivity; D005110:Extracellular Space / Q000378:metabolism; D028581:Lanthanoid Series Elements / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D014981:Xenopus
D015220:Calcium Channels; D018118:Chloride Channels; D002712:Chlorides; D047630:Depsipeptides; D028581:Lanthanoid Series Elements; D009025:Morpholines; C004456:beauvericin; C085610:lateritin; D002118:Calcium