著者

Nagase Masahiro Alam M.Murshedul Tsushima Akiko YOSHIZAWA Takumi SAKATO Nobuo

出版者

社団法人日本農芸化学会

雑誌

Bioscience, biotechnology, and biochemistry (ISSN:09168451)

巻号頁・発行日

vol.65, no.8, pp.1741-1747, 2001-08-23

参考文献数

41

被引用文献数

2 49

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The molecules participating in apoptosis induced by T-2 toxin in human leukemia HL-60 cells were investigated. The rank order of the potency of trichothecene mycotoxins to induce internucleosomal DNA fragmentation was found to be T-2, satratoxin G, roridin A >> diacetoxyscirpenol > baccharin B-5 > > nivalenol, deoxynivalenol, 3-acetyldeoxynivalenol, fusarenon-X, baccharin B-4 = vehicle control. Western blot analysis of caspase-3 in T-2-treated cells clearly indicated the appearance of its catalytically active fragment of 17-kDa. Increased caspase-3 activity was also detected by using a fluorogenic substrate, DEVD-AMC. Next, cells exposed to T-2 led to cleavage of PARP from its native 116-kDa form to the 85-kDa product. Moreover, DFF-45/ICAD were cleaved to give a 12.5-kDa fragment via T-2 treatment. T-2 caused the release of cytochrome c from mitochondria into the cytosol. Increased enzymic activity of caspase-9 on LEHD-AMC was shown. These data indicate that T-2-induced apoptosis involves activation of caspase-3 and DFF-40/CAD through cytosolic accumulation of cytochrome c along with caspase-9 activation.