Ennamany R, Lavergne J P, Reboud J P, Dirheimer G, Creppy E E
Laboratory of Toxicology and Applied Hygiene, University of Bordeaux 2, France.
Toxicology. 1995 Jun 26;100(1-3):51-5. doi: 10.1016/0300-483x(95)03058-n.
Bolesatine is a potent cytotoxic glycoprotein purified from Boletus satanas Lenz, which has previously been shown to be an inhibitor of protein synthesis in several in vitro systems and in vivo. For a better understanding of its mechanism of action on protein synthesis at the ribosomal level, rat liver ribosomes were pretreated with bolesatine (1 to 10 micrograms) added to in vitro polyuridylic acid (poly(U)) translation systems before and after washing. The fact that ribosomes were still active confirmed that bolesatine cannot be included in the group of protein synthesis inhibitors of plant origin, known as ribosome-inactivating proteins (RIPs). The effect of bolesatine on the EF-2 elongation factor and post-ribosomal fraction was then studied in vitro. The results indicated that bolesatine does not have a direct effect on elongation factors, but hydrolyses the nucleoside triphosphates, GTP (80% to 90%, respectively for 1 to 10 micrograms) and ATP (10% to 40%, respectively for 1 to 10 micrograms), with consequent inhibition of protein synthesis. Thus, bolesatine should be classified as a nucleoside triphosphate phosphatase, rather than as a direct inhibitor of protein synthesis. The study of the effect of bolesatine on the EF-2 factor revealed that the mechanism whereby bolesatine affects protein synthesis probably involves GTP hydrolysis rather than EF-2 inhibition.
鬼笔毒素是一种从毒红菇中纯化得到的强效细胞毒性糖蛋白，此前已证明它在多种体外系统和体内均是蛋白质合成的抑制剂。为了更好地理解其在核糖体水平上对蛋白质合成的作用机制，在洗涤前后，将鬼笔毒素（1至10微克）添加到体外多聚尿苷酸（poly(U)）翻译系统中，对大鼠肝脏核糖体进行预处理。核糖体仍具有活性这一事实证实，鬼笔毒素不能归入植物来源的蛋白质合成抑制剂类别，即核糖体失活蛋白（RIPs）。随后在体外研究了鬼笔毒素对EF - 2延伸因子和核糖体后组分的影响。结果表明，鬼笔毒素对延伸因子没有直接作用，但能水解核苷三磷酸，即GTP（1至10微克时分别为80%至90%）和ATP（1至10微克时分别为10%至40%），从而抑制蛋白质合成。因此，鬼笔毒素应归类为核苷三磷酸磷酸酶，而非蛋白质合成的直接抑制剂。对鬼笔毒素对EF - 2因子影响的研究表明，鬼笔毒素影响蛋白质合成的机制可能涉及GTP水解而非EF - 2抑制。
