Marzella L, Glaumann H
Lab Invest. 1980 Jan;42(1):8-17.
The administration of vinblastine sulfate to rats causes an increase in degradation of liver proteins and lipids as measured in vitro by the release of trichloroacetic acid-soluble products. In mitochondrial-lysosomal fractions both lipolysis and proteolysis increase. Postmicrosomal supernatants (cytosol) also show an increase in lipolysis. Little or no enhancement of degradation occurs in the microsomal fraction. The stimulation of degradation by vinblastine is dose-related and is associated with increased lysosomal fragility. Degradation in vitro in the vinblastine model persists longer than in the control. No alterations either in the recovery of cell fractions or in the distribution of lysosomal enzymes are seen after vinblastine treatment. The increase in proteolysis induced by vinblastine can be completely prevented by pretreating the rats with either low or high doses of cycloheximide. Biochemical characterization by use of an inhibitor (iodoacetamide) of cathepsins and by use of ammonium chloride suggests that the increased proteolysis seen after vinblastine is related to increased sequestration of substrate into the lysosomal pool. Our studies do not support the notion that in the liver vinblastine impairs fusion between autophagosomes and preexisting primary or secondary lysosomes during the time points studied. The stimulation of both proteolysis and lipolysis in the liver lysosomes of rats treated with vinblastine provides an experimental model for the studies on mechanisms of intralysosomal degradation of cell constituents.
给大鼠注射硫酸长春碱会导致肝脏蛋白质和脂质降解增加，这可通过体外测量三氯乙酸可溶性产物的释放来确定。在线粒体 - 溶酶体组分中，脂解和蛋白水解均增加。微粒体后上清液（胞质溶胶）中的脂解也增加。微粒体组分中降解几乎没有增强或没有增强。长春碱对降解的刺激与剂量相关，并且与溶酶体脆性增加有关。长春碱模型中的体外降解持续时间比对照更长。长春碱处理后，细胞组分的回收率或溶酶体酶的分布均未出现改变。用低剂量或高剂量的环己酰亚胺预处理大鼠可完全防止长春碱诱导的蛋白水解增加。使用组织蛋白酶抑制剂（碘乙酰胺）和氯化铵进行的生化特性分析表明，长春碱后观察到的蛋白水解增加与底物更多地隔离到溶酶体池中有关。我们的研究不支持这样的观点，即在研究的时间点，长春碱在肝脏中会损害自噬体与先前存在的初级或次级溶酶体之间的融合。长春碱处理的大鼠肝脏溶酶体中蛋白水解和脂解的刺激为研究细胞成分的溶酶体内降解机制提供了一个实验模型。
