Gonias S L, Pizzo S V
Biochim Biophys Acta. 1981 Dec 4;678(2):268-74. doi: 10.1016/0304-4165(81)90216-6.
Clearance studies were performed in mice using alpha 2-macroglobulin (alpha 2M), alpha 2M-trypsin complex and alpha 2M-CH3NH2 complex. All three species were incubated with cis-dichlorodiamine platinum(II) (cis-DDPt) at concentrations between 9.0 microM and 1.67 mM for 4 h and then dialyzed. The clearance rate of native alpha 2M was unchanged following incubation with cis-DDPt. alpha 2M-trypsin and alpha 2M-CH3NH2 cleared rapidly from the circulation; however, reaction with cis-DDPt significantly decreased the plasma elimination rate of both complexes. Non-denaturing gel electrophoresis and alpha 2M activity assays demonstrated relative stability following incubations with cis-DDPt which markedly altered clearance. Evidence for cis-DDPt crosslinking of alpha 2M subunits was obtained; however, whether this crosslinking is involved in altered clearance remains undetermined. Iodoacetamide treatment of alpha 2M did not duplicate the effect of cis-DDPt on alpha 2M clearance, nor did it inhibit the effect of cis-DPPt on alpha 2M clearance. Plasma elimination of alpha 2M complex was also unaltered by pretreatment of mice with intravenous free cis-DDPt.
使用α2-巨球蛋白（α2M）、α2M-胰蛋白酶复合物和α2M-CH3NH2复合物在小鼠身上进行清除率研究。将这三种物质与顺式二氯二氨铂（II）（顺铂）在9.0微摩尔/升至1.67毫摩尔/升的浓度下孵育4小时，然后进行透析。与顺铂孵育后，天然α2M的清除率没有变化。α2M-胰蛋白酶和α2M-CH3NH2从循环中迅速清除；然而，与顺铂反应显著降低了两种复合物的血浆清除率。非变性凝胶电泳和α2M活性测定表明，与顺铂孵育后具有相对稳定性，这显著改变了清除率。获得了顺铂使α2M亚基交联的证据；然而，这种交联是否与清除率改变有关仍未确定。用碘乙酰胺处理α2M既不能复制顺铂对α2M清除率的影响，也不能抑制顺铂对α2M清除率的影响。静脉注射游离顺铂预处理小鼠对α2M复合物的血浆清除也没有影响。
