Dietary protein deficiency reduces lysosomal and nonlysosomal ATP-dependent proteolysis in muscle.
When rats are fed a protein deficient (PD) diet for 7 days, rates of proteolysis in skeletal muscle decrease by 40-50% (N. E. Tawa, Jr., and A. L. Goldberg. Am. J. Physiol. 263 (Endocrinol. Metab. 26): E317-325, 1992). To identify the underlying biochemical adaptations, we measured different proteolytic processes in incubated muscles. The capacity for intralysosomal proteolysis, as shown by sensitivity to methylamine or lysosomal protease inhibitors, fell 55-75% in muscles from PD rats. Furthermore, extracts of muscles of PD rats showed 30-70% lower activity of many lysosomal proteases, including cathepsins B, H, and C, and carboxypeptidases A and C, as well as other lysosomal hydrolases. The fall in cathepsin B and proteolysis was evident by 3 days on the PD diet, and both returned to control levels 3 days after refeeding of the normal diet. In muscles maintained under optimal conditions, 80-90% of protein breakdown occurs by nonlysosomal pathways. In muscles of PD rats, this ATP-dependent process was also 40-60% slower. Even though overall proteolysis decreased in muscles of PD rats, their capacity for Ca(2+)-dependent proteolysis increased (by 66%), as did the activity of the calpains (+150-250%). Thus the lysosomal and the ATP-dependent processes decrease coordinately and contribute to the fall in muscle proteolysis in PD animals.
Tawa
N E
NE
Department of Surgery, Beth Israel Hospital, Boston 02215.
Kettelhut
I C
IC
Goldberg
A L
AL
D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000502:physiology; D004044:Dietary Proteins; D008247:Lysosomes / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D009132:Muscles / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism*; D011488:Protein Deficiency / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D004044:Dietary Proteins; D000255:Adenosine Triphosphate; D010447:Peptide Hydrolases; D002118:Calcium