Inhibitors and pathways of hepatocytic protein degradation.

摘要: On the basis of experiments using amino acids and various inhibitors (lysosomotropic amines, leupeptin, chymostatin, vanadate, vinblastine, anoxia, methylaminopurines), five different modes endogenous protein degradation in isolated rat hepatocytes can be distinguished. The two non-lysosomal (amine-resistant) mechanisms preferentially degrade relatively labile (short-lived) proteins: one these is energy-dependent chymostatin-sensitive, other not. Of three lysosomal (amine-sensitive) mechanisms, one--quantitatively minor--is acid-resistant degrades proteins. acid-sensitive each seen account for about one-half stable (long-lived) proteins; them suppressed by leucine apparently corresponds to formation electron microscopically visible autophagosomes; may represent a type autophagy, inhibited asparagine glutamine. A new class inhibitors, purine derivatives (methylated 6-aminopurines, 6-mercaptopurines) appear specifically suppress autophagic/lysosomal degradation, help further elucidate autophagy.