SELECTIVE ANTIMITOCHONDRIAL AGENTS INHIBIT CALMODULIN
SELECTIVE ANTIMITOCHONDRIAL AGENTS INHIBIT CALMODULIN
复制标题
DOI：
10.1016/0006-291x(86)90032-x
复制
发表时间：
1986-03-13
影响因子：
3.1
通讯作者：
HAIT, WN
中科院分区：
文献类型：
--
作者：
BODDEN, WL;PALAYOOR, ST;HAIT, WN
已知某些阳离子亲脂性化合物在肿瘤线粒体中选择性地降解并抑制能量产生。由于这些物质与已知的钙调蛋白抑制剂在结构上相似，我们研究了罗丹明-123或双-4-氨基喹哪啶是否可以拮抗钙调蛋白的作用。罗丹明-123（IC 50 = 58 μ M）和地喹铵（IC 50 = 1 μ M）抑制钙调素刺激的环核苷酸磷酸二酯酶的活性。丙炔铵是一种类似于地喹铵的化合物，除了具有连接两个未取代的喹啉环的3个而不是10个碳烷基桥之外，没有抑制作用。动力学分析表明，地喹铵竞争性抑制钙调素对磷酸二酯酶的激活。我们还研究了化合物对C6星形细胞瘤细胞系的抗增殖作用。罗丹明-123和地喹铵对该细胞株的增殖有抑制作用，而丙啶铵则无此作用。这些研究表明，罗丹明-123和地喹铵是钙调素拮抗剂，并抑制细胞增殖。
Certain cationic-lipophilic compounds are known to selectively accumlate in tumor mitochondria and inhibit energy production. Since these substances bear a structural resemblance to known inhibitors of calmodulin, we studied whether rhodamine-123 or a bis-4-aminoquinaldinium could antagonize the action of calmodulin. Rhodamine-123 (IC50 = 58 .mu.M) and dequalinium (IC50 =1.mu.M) inhibited the activity of a calmodulin-stimulated cyclic nucleotide phosphodiesterase. Propylinium, a compound similar to dequalinium except for having a 3 rather than 10 carbon alkyl bridge connecting two non-substituted quinoline rings, had no inhibitory effect. Kinetic analysis showed that dequalinium competitively inhibited calmodulin''s activation of phosphodiesterase. We also studied the antiproliferative effects of the compounds on the C6 astrocytoma cell line. Rhodamine-123 and dequalinium inhibited the proliferation of this cell line while propylinium had no effect. These studies demonstrate that rhodamine-123 and dequalinium are calmodulin-antagonists and inhibit cellular proliferation.