Beauvericin activates Ca2+-activated Cl- currents and induces cell deaths in Xenopus oocytes via influx of extracellular Ca 2+

Chih Yung Tang, Yi Wen Chen, Guey Mei Jow, Cheng Jen Chou, Chung Jiuan Jeng*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

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 Ca2+ concentration ([Ca2+]i). Despite the fact that beauvericin may activate extracellular Ca2+ influx, beauvericin-induced cell deaths has been suggested to be exclusively due to Ca2+ release from internal Ca2+ stores. We endeavored to elucidate the mechanism of beauvericin-induced [Ca2+]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 Ca2+-activated Cl- currents (ICl,Ca) Removal of extracellular Ca2+, 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 Ca2+, cytotoxicity-induced by 10 and 30 μM, but not 50 μM, of beauvericin was significantly diminished. Our results are consistent with the idea that beauvericin induces extracellular Ca2+ influx, which in turn activates ICl,Ca and contributes to beauvericin-induced cell deaths in Xenopus oocytes.

Original languageEnglish
Pages (from-to)825-833
Number of pages9
JournalChemical Research in Toxicology
Volume18
Issue number5
DOIs
StatePublished - May 2005

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