+1 Recommend
0 collections
      • Record: found
      • Abstract: found
      • Article: not found

      Administration of endotoxin, tumor necrosis factor, or interleukin 1 to rats activates skeletal muscle branched-chain alpha-keto acid dehydrogenase.

      The Journal of clinical investigation

      pharmacology, Tumor Necrosis Factor-alpha, Salmonella enteritidis, Reference Values, Recombinant Proteins, Rats, Inbred Strains, Rats, metabolism, enzymology, drug effects, Muscles, Multienzyme Complexes, Male, Lipopolysaccharides, blood, Leucine, Kinetics, Ketone Oxidoreductases, Interleukin-1, Enzyme Activation, Endotoxins, Corticosterone, Animals, Amino Acids, 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)

      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.


          Protein catabolic states (i.e., sepsis and trauma) are thought to be associated with accelerated oxidation of branched-chain amino acids (BCAA). Branched-chain alpha-keto acid dehydrogenase (BCKAD), the rate-limiting enzyme for BCAA oxidation by muscle, is regulated by phosphorylation/dephosphorylation. Skeletal muscle BCKAD was only 2-4% active in control rats. Intravenous injection of Salmonella enteritidis endotoxin (0.25-10 mg/kg) did not change total BCKAD activity, but increased the percent active enzyme in muscle three- to four-fold in 4-6 h. Identical results were observed in adrenalectomized rats pretreated with one dose of alpha-methylprednisolone (2.5 mg/kg i.p.) 30-60 min before saline or endotoxin injection, indicating that endotoxin's effect was not mediated by hypersecretion of adrenal hormones. Cortisone pretreatment of normal rats (100 mg/kg per d) for 2 d prevented endotoxin-induced activation of muscle BCKAD, suggesting that endogenous secretion products mediated BCKAD activation by endotoxin. Human recombinant tumor necrosis factor-alpha and/or IL-1 beta or alpha (50 micrograms/kg) increased muscle BCKAD activation two- to fourfold in normal rats 4-6 h after intravenous injection. We conclude that cytokine-mediated activation of muscle BCKAD may contribute to accelerated BCAA oxidation in septicemia.

          Related collections

          Author and article information



          Comment on this article