Mycotoxin Prevention and Applied Microbiology Research Unit, Agricultural Research Service, U.S. Department of Agriculture, Peoria, IL 61604, USA.
Toxins (Basel). 2018 Jul 10;10(7):285. doi: 10.3390/toxins10070285.
Cycopiazonic acid (CPA) is a neurotoxin that acts through inhibition of the sarco(endo)plasmic reticulum Ca-ATPase (SERCA). CPA blocks the calcium access channel of the enzyme. The inhibition may involve the binding of CPA with a divalent cation such as Mg. The potential for CPA to act as a chelator also has implications for methods to detect this toxin. Certain of the lanthanide metals undergo a dramatic increase in luminescence upon coordination with small molecules that can transfer excitation energy to the metal. This report is the first to describe the coordination of CPA with lanthanide metals, resulting in a substantial enhancement of their luminescence. The luminescence expressed was dependent upon the type of lanthanide, its concentration, and the environment (solvent, water content, pH). Based upon the phenomenon, a competitive assay was also developed wherein terbium (Tb) and a series of metal cations competed for binding with CPA. With increasing cation concentration, the luminescence of the CPA/Tb complex was inhibited. The chlorides of ten metals were tested. Inhibition was best with Cu, followed by Co, Al, Fe, Mn, Au, Mg, and Ca. Two cations in oxidation state one (Na⁺, K⁺) did not inhibit the interaction significantly. The interaction of CPA with lanthanides provides a novel recognition assay for this toxin. It also provides a novel way to probe the binding of CPA to metals, giving insights into CPA’s mechanism of action.
环匹阿尼酸（CPA）是一种神经毒素，通过抑制肌浆网（内质网）Ca-ATP 酶（SERCA）起作用。CPA 阻断酶的钙进入通道。这种抑制可能涉及 CPA 与二价阳离子（如 Mg）的结合。CPA 作为螯合剂的潜力也对检测这种毒素的方法有影响。某些镧系金属在与可以将激发能传递给金属的小分子配位时，其发光会显著增加。本报告首次描述了 CPA 与镧系金属的配位，导致其发光显著增强。表达的发光取决于镧系金属的类型、其浓度和环境（溶剂、含水量、pH 值）。基于这一现象，还开发了一种竞争性测定法，其中铽（Tb）和一系列金属阳离子竞争与 CPA 结合。随着阳离子浓度的增加，CPA/Tb 配合物的发光被抑制。测试了十种金属的氯化物。Cu 的抑制效果最好，其次是 Co、Al、Fe、Mn、Au、Mg 和 Ca。两种处于氧化态一的阳离子（Na⁺，K⁺）没有显著抑制相互作用。CPA 与镧系元素的相互作用为这种毒素提供了一种新颖的识别测定法。它还为研究 CPA 与金属的结合提供了一种新方法，深入了解 CPA 的作用机制。
