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通过低渗处理、皂苷和抗癌阿魏菌素使红细胞通透化。

Red blood cell permeabilization by hypotonic treatments, saponin, and anticancer avicins.

作者信息

Arias Mauricio, Quijano Jairo C, Haridas Valsala, Gutterman Jordan U, Lemeshko Victor V

机构信息

Escuela de Física, Facultad de Ciencias, Universidad Nacional de Colombia, Sede Medellín, Colombia.

出版信息

Biochim Biophys Acta. 2010 Jun;1798(6):1189-96. doi: 10.1016/j.bbamem.2010.03.018. Epub 2010 Mar 24.

Abstract

Plasma membrane permeabilization by saponin and anticancer avicins was studied using light dispersion measurements, since high correlation between light dispersion changes and hemolysis has been demonstrated. Nevertheless, we observed that rat red blood cell swelling in moderately hypotonic media was accompanied by up to 20% decrease of light dispersion, when hemolysis was not yet detectable. Avicin G and avicin D were significantly more efficient than saponin in inducing cytotoxicity in PC3 human prostate cancer cells. We found that the preincubation of avicins with the plasma membrane, but not with the cytosolic fraction of previously lysed red blood cells, completely protected fresh cells against permeabilization. The data suggest that the plasma membrane can tightly bind the avicins, but not the saponin. Using the "osmotic protection" method with 100mOsm PEGs of increasing molecular weight in isotonic media, the size of the pores generated by avicin G and avicin D in the plasma membrane was estimated to be higher than the hydrodynamic radius of PEG-8000. The obtained results indicate that the anticancer activity of avicin G and avicin D could be related, at least partially, to their high ability to permeabilize biological membranes. These data might represent interest for possible applications of these anticancer drugs in vivo.

摘要

由于已证明光散射变化与溶血之间存在高度相关性,因此使用光散射测量法研究了皂苷和抗癌阿维菌素对质膜的通透作用。然而,我们观察到,在尚未检测到溶血的情况下,大鼠红细胞在中度低渗介质中肿胀时,光散射会降低多达20%。阿维菌素G和阿维菌素D在诱导PC3人前列腺癌细胞的细胞毒性方面比皂苷明显更有效。我们发现,阿维菌素与质膜预孵育,而不是与先前裂解的红细胞的胞质部分预孵育,能完全保护新鲜细胞不被通透。数据表明,质膜可以紧密结合阿维菌素,但不能结合皂苷。在等渗介质中使用分子量不断增加的100mOsm聚乙二醇的“渗透保护”方法,估计阿维菌素G和阿维菌素D在质膜上产生的孔的大小高于聚乙二醇-8000的流体动力学半径。所得结果表明,阿维菌素G和阿维菌素D的抗癌活性可能至少部分与其使生物膜通透的高能力有关。这些数据可能对这些抗癌药物在体内的可能应用具有重要意义。

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