Transient elevation of intracellular calcium ion levels as an early event in T-2 toxin-induced apoptosis in human promyelotic cell line HL-60

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Abstract
Recently we have reported that T‐2 toxin, a trichothecene mycotoxin produced by Fusarium species, is a potent inducer of apoptosis in the human promyelotic cell line HL‐ 60. To clarify the signal transduction pathway of apoptosis primed by T‐2 toxin, T‐2 toxin‐induced apoptosis was investigated in detail using confocal laser microscopy and flow cytometry. Apoptosis in HL‐60 cells induced by T‐2 toxin was dose dependent when the cells were treated with concentrations of 5–100 ng/ml for more than 2 hr. The apoptosis proceeds through various cell cycle stages of HL‐60 cells. Prior to apoptosis, the intracellular calcium ion (Ca++1) level was markedly elevated within 3–5 min after exposure to T‐2 toxin and returned to normal level thereafter. A well‐known chelator for Ca+++1, ethylene‐N,N,N′,N′‐tetraacetic acid 4K acetoxymethyl ester (BAPTA‐AM), a Ca++‐dependent endonuclease inhibitor ZnCl2, and calpain inhibitor I sharply blocked T‐2 toxin‐induced apoptosis. These results strongly suggest that the Ca++ signal triggered by T‐2 toxin is transduced by the activation of endonuclease and protease, and ultimately evokes apoptosis.

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