Escuela de Física, Facultad de Ciencias, Universidad Nacional de Colombia, Sede Medellín, Calle 59A, No 63-20, Medellín, Colombia.
Arch Biochem Biophys. 2010 Jan 15;493(2):213-20. doi: 10.1016/j.abb.2009.11.004. Epub 2009 Nov 10.
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 3.6muM 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 mitochondrial 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.
文献报道，带正电荷的七肽（KLAKLAK）（2）与七聚精氨酸细胞传递载体 r7 和 R7（肽 r7-kla 和 R7-KLA）融合后，其作为线粒体损伤剂的抗癌活性增强。我们证明 3.6μM 的 r7-kla 或 R7-KLA，但不是 kla，可显著通透加能的大鼠肝线粒体的内外膜。此外，r7-kla 或 R7-KLA 诱导线粒体聚集，从而抑制代谢活性。这些肽对红细胞质膜的通透性也表现出电位依赖性机制。获得的结果表明，抗癌多阳离子肽的多聚精氨酸细胞传递载体不仅增加了它们对生物膜的直接电位依赖性通透，而且还产生了引起线粒体聚集的能力，这是这些肽细胞毒性作用的新机制。
