Stimulation of autophagic protein degradation by nutrient deprivation in a differentiated murine teratocarcinoma (F9 12-1a) cell line.
We have evaluated the participation of the lysosomal degradation pathway in the increased protein degradation induced by nutrient deprivation in transformed cells. To this end we used a clone, 12-1a, derived from a murine teratocarcinoma cell line (F9 12-1) induced to differentiate by culture in retinoic acid. Culture of 12-1a cells, prelabeled with L-[U-14C]valine, in nutrient-deprived medium (Hanks' balanced salt solution plus Ca++) stimulated the protein degradation rate from 0.9% hr to 1.4% hr. Morphometric analysis demonstrated that during nutrient deprivation, the volume density of lysosomes increased 3-fold; the numerical density of lysosomes increased 2-fold; the mean area of lysosomal profiles increased 1.7-fold (1.40 microns2 vs 0.81 microns2). The volume density and numerical density of the dense bodies tended to decrease by approximately 60% without any change in the mean volume of the dense bodies. These data indicate that nutrient deprivation increases protein degradation in transformed cells by increasing the sequestration of cytoplasm into the lysosomes. The decrease in the number of dense bodies indicates that these structures (also termed residual bodies) are functional in transformed cells and merge with the lysosomes to provide more degradative enzymes to enhance proteolysis. This study provides direct evidence that serum factors and nutrients play a crucial role in modulation of lysosomal protein degradation in transformed cells.
Lee
H K
HK
Department of Pathology, School of Medicine, University of Maryland, Baltimore 21201.
Myers
R A
RA
Marzella
L
L
D000818:Animals; D001343:Autophagy; D003470:Culture Media; D008247:Lysosomes / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D009753:Nutritive Value; D010447:Peptide Hydrolases / Q000378:metabolism; D010587:Phagocytosis; D011506:Proteins / Q000378:metabolism*; D013724:Teratoma / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D014407:Tumor Cells, Cultured
D003470:Culture Media; D011506:Proteins; D010447:Peptide Hydrolases