PROTEIN DEGRADATION IN CULTURED CELLS

作者：Maurice Wibo, Brian D. Poole · 发表于：The Journal of Cell Biology · 年份：1974 · DOI：10.1083/jcb.63.2.430 · 被引用次数：601 · 研究领域：Enzyme function and inhibition、Enzyme Catalysis and Immobilization、Protein Hydrolysis and Bioactive Peptides

The degradation of cellular proteins in fibroblasts, both those of rapid and those of slow turnover rates, was inhibited by low concentrations of chloroquine or neutral red in the medium. Cells inhibited by chloroquine can be inhibited further by fluoride. Chloroquine was taken up by the fibroblasts and the concentration in the cells reached several hundred times that in the medium. Isopycnic fractionation studies showed that within the cells the chloroquine was concentrated in the lysosomes, and that these chloroquine-containing lysosomes had a lower equilibrium density than the lysosomes of untreated cells. Chloroquine, at concentrations attained inside the lysosomes, inhibited cathepsin B(1) but not cathepsin D. It is concluded that chloroquine impairs the breakdown of cellular proteins after these have entered the lysosome system, probably through inhibition of cathepsin B(1).