Potential-dependent membrane permeabilization and mitochondrial aggregation caused by anticancer polyarginine-KLA peptides
Potential-dependent membrane permeabilization and mitochondrial aggregation caused by anticancer polyarginine-KLA peptides
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DOI：
10.1016/j.abb.2009.11.004
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发表时间：
2010-01-15
影响因子：
3.9
通讯作者：
Lemeshko, Victor V.
中科院分区：
文献类型：
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作者：
Lemeshko, Victor V.
聚阳离子肽（KLAKLAK）（2）作为可能的大肠杆菌损伤剂，称为KLA（L-型）或kla（D-型），其抗癌活性已通过与七精氨酸细胞递送载体r7和R7（分别为肽r7-kla和R7-KLA）融合而增加，如文献中所示。我们证明，3.6 μ M的r7-KLA或R7-KLA，但不是KLA，引起显着的通透的内和外膜的通电大鼠肝线粒体。此外，r7-kla或R7-KLA诱导线粒体聚集，从而导致代谢活性的抑制。还观察到红细胞质膜通过这些肽透化线粒体内膜的电位依赖性机制。所获得的结果表明，抗癌聚阳离子肽的聚精氨酸细胞递送载体不仅增加了它们对生物膜的直接电位依赖性透化，而且还产生了引起线粒体聚集的能力，作为这些肽的细胞毒性作用的新机制。(C)2009爱思唯尔公司All rights reserved.
The anticancer activity of the polycationic peptide (KLAKLAK)(2), as a possible mitochondria-damaging agent, named KLA (L-form) or kla (D-form), has been increased by the fusion with hepta-arginine cell delivery vectors r7 and R7 (peptides r7-kla and R7-KLA, respectively), as shown in the literature. We demonstrated that 3.6 mu M r7-kla or R7-KLA, but not kla, caused significant permeabilization of the inner and the outer membranes of energized rat liver mitochondria. In addition r7-kla or R7-KLA induced mito, chondrial aggregation, thus causing the inhibition of metabolic activity. Potential-dependent mechanism of permeabilization of the inner mitochondrial membrane by these peptides was also observed for the plasma membrane of red blood cells. The obtained results suggest that polyarginine cell delivery vectors of anticancer polycationic peptides not only increase their direct potential-dependent permeabilization of biological membranes, but also create the capacity to cause aggregation of mitochondria, as a new mechanism of cytotoxic action of these peptides. (C) 2009 Elsevier Inc. All rights reserved.