title: Control of protein degradation in muscle by prostaglandins, Ca2+, and leukocytic pyrogen (interleukin 1).
abstract: Protein degradation in skeletal muscle increases with fever and sepsis. Our studies indicate that prostaglandin E2 (PGE2) is an important regulator of muscle proteolysis that seems to signal this increase in fever. When rat skeletal or cardiac muscles were incubated with arachidonate, rates of protein breakdown rose and protein balance became more negative. Aspirin or indomethacin, which prevented synthesis of PGE2, markedly reduced this effect. By itself PGE2 stimulated proteolysis without altering protein synthesis. PGE2 seems to increase proteolysis in the lysosomes, inasmuch as leupeptin and Ep-475 inhibit this response. These inhibitors inactivate lysosomal thiol proteases in the muscles without affecting the Ca2+-activated protease. (In fact, complete inactivation of the latter enzyme with mersalyl did not reduce overall proteolysis in the muscles). When muscles from feverish rats were incubated in vitro, they showed greater protein breakdown and PGE2 synthesis than muscles from normal animals. Addition of indomethacin eliminated this difference. Leukocytic pyrogen (interleukin 1), a protein released by monocytes that signals the onset of fever, also seems to signal increased muscle PGE2 synthesis and muscle proteolysis. This protein enhanced both processes dramatically in the isolated muscles. These findings suggest that cyclooxygenase inhibitors may be useful in the treatment of patients showing excessive protein breakdown.
mesh_terms: D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002154:Calpain; D016861:Cyclooxygenase Inhibitors; D015232:Dinoprostone; D010450:Endopeptidases / Q000378:metabolism; D005334:Fever / Q000378:metabolism; D007375:Interleukin-1 / Q000502:physiology*; D008247:Lysosomes / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism*; D009132:Muscles / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D011458:Prostaglandins E / Q000502:physiology*; D051381:Rats; D018805:Sepsis / Q000378:metabolism
chemical_list: D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D007375:Interleukin-1; D009124:Muscle Proteins; D011458:Prostaglandins E; D016718:Arachidonic Acid; D010450:Endopeptidases; D010447:Peptide Hydrolases; D002154:Calpain; D015232:Dinoprostone; D002118:Calcium