Madsen K M, Christensen E I
Lab Invest. 1978 Feb;38(2):165-74.
The effect of mercury on renal lysosomal protein digestion was studied after administration of mercury in vitro and in vivo. Mercuric chloride or methylmercury chloride was added in vitro to lysosomal enzymes isolated from normal rats, and subsequently, digestion experiments were carried out using 125I-labeled lysozyme or cytochrome c as substrate proteins. Both mercury compounds produced a concentration-dependent inhibition of the degradation of the proteins, mercuric chloride being the strongest inhibitor. Mercuric chloride was also administered to rats in vivo for 5 to 8 months. Renal lysosomal enzymes from these animals also had a decreased ability to digest for the two substrate proteins. Furthermore, the digestion of lysozyme intravenously injected into mercury-intoxicated rats was decreased in renal cortical slices incubated in vitro. Electron microscope autoradiography showed that intravenously injected labeled lysozyme was located primarily over lysosomes in proximal tubule cells 1 hour after injection in both control animals and mercury-intoxicated rats. These results suggest a decreased catabolism of low molecular weight proteins in the kidney during chronic mercury intoxication.
在体外和体内给予汞后,研究了汞对肾溶酶体蛋白消化的影响。在体外,将氯化汞或甲基氯化汞添加到从正常大鼠分离的溶酶体酶中,随后,以125I标记的溶菌酶或细胞色素c作为底物蛋白进行消化实验。两种汞化合物均产生浓度依赖性的蛋白质降解抑制作用,其中氯化汞是最强的抑制剂。还对大鼠进行了为期5至8个月的体内氯化汞给药。这些动物的肾溶酶体酶对两种底物蛋白的消化能力也有所下降。此外,在体外培养的肾皮质切片中,静脉注射到汞中毒大鼠体内的溶菌酶的消化作用降低。电子显微镜放射自显影显示,在对照动物和汞中毒大鼠中,静脉注射标记的溶菌酶在注射后1小时主要位于近端小管细胞的溶酶体上。这些结果表明,在慢性汞中毒期间,肾脏中低分子量蛋白质的分解代谢减少。