Effect of amino acids and cycloheximide on changes caused by vinblastine, leupeptin and methylamine in the autophagic/lysosomal system of mouse hepatocytes in vivo.
The number of autophagic vacuoles in hepatocytes of 24 h fasted mice in vivo increased manyfold following the administration of vinblastine, leupeptin and methylamine. The effect of each chemical is characterized by the predominance of a certain kind of vacuole. Vinblastine treatment is accompanied by a large proportion of vacuoles containing morphologically unaltered organelles, leupeptin causes preferential accumulation of dense and complex vacuoles, methylamine administration produces mostly large, electron-lucent, swollen vacuoles. The amounts of segregated and accumulated cytoplasmic material, expressed as percentage cytoplasm per hour, were 0.84%, 2.08% and 0.74% following vinblastine, leupeptin and methylamine treatment respectively. The actual rate of segregation was probably higher than this. Inhibition of degradation of the sequestered cytoplasmic material is proposed to be a main factor in the increase in the size of the autophagic/lysosomal compartment. Treatment with cycloheximide or exogenously added mixture of amino acids cut down the size of the autophagic/lysosomal system in control cells and strongly inhibited the accumulation caused by vinblastine, leupeptin and methylamine.
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D003513:Cycloheximide / Q000494:pharmacology; D007976:Leupeptins / Q000494:pharmacology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008247:Lysosomes / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008744:Methylamines / Q000494:pharmacology; D051379:Mice; D009940:Organoids / Q000187:drug effects*; D010587:Phagocytosis / Q000187:drug effects*; D011506:Proteins / Q000378:metabolism*; D014617:Vacuoles / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D014747:Vinblastine / Q000494:pharmacology
D000596:Amino Acids; D007976:Leupeptins; D008744:Methylamines; D011506:Proteins; D014747:Vinblastine; D003513:Cycloheximide; C027451:methylamine; C032854:leupeptin