Chen Ku-Chung, Kao Pei-Hsiu, Lin Shinne-Ren, Chang Long-Sen
Institute of Biomedical Sciences, National Sun Yat-Sen University-Kaohsiung Medical University Joint Research Center, National Sun Yat-Sen University, Kaohsiung 804, Taiwan.
Toxicon. 2007 Nov;50(6):816-24. doi: 10.1016/j.toxicon.2007.06.011. Epub 2007 Jun 27.
In order to dissect out whether multiple activities of cardiotoxins (CTXs) are connected, to some extent, with each other, studies on reduced and S-carboxyamidomethylated (Rcam) Naja naja atra CTX3 were carried out in the present study. Although both CTX3 and Rcam-CTX3 induced apoptotic death of PC-3 cells as evidenced by propodium iodide/annexin V double staining, degradation of procaspases and DNA fragmentation, the cytotoxicity of Rcam-CTX3 was mostly 100-fold lower than that noted with native toxin. However, Rcam-CTX3 retained approximately 38% of the membrane-damaging activity of native toxin as revealed by the decrease in calcein self-quenching from phospholipid vesicles. These results are likely to reflect that the mechanism of cytotoxicity by CTX3 is not heavily dependent on its membrane-perturbing effect, and suggest that the structural elements within CTX3 responsible for the two activities are probably separated.
为了剖析心脏毒素（CTXs）的多种活性在某种程度上是否相互关联，本研究对还原型和S-羧酰胺甲基化（Rcam）的眼镜蛇毒心脏毒素3（Naja naja atra CTX3）展开了研究。尽管通过碘化丙啶/膜联蛋白V双重染色、半胱天冬酶原降解和DNA片段化证明，CTX3和Rcam-CTX3均可诱导PC-3细胞发生凋亡性死亡，但Rcam-CTX3的细胞毒性大多比天然毒素低100倍。然而，如通过磷脂囊泡中钙黄绿素自淬灭的降低所显示，Rcam-CTX3保留了约38%的天然毒素膜损伤活性。这些结果可能反映出CTX3的细胞毒性机制并非严重依赖于其膜扰动效应，并表明CTX3中负责这两种活性的结构元件可能是分开的。
