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

摘要: 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 by muscle, is regulated phosphorylation/dephosphorylation. Skeletal muscle BCKAD was only 2-4% active in control rats. Intravenous injection Salmonella enteritidis endotoxin (0.25-10 mg/kg) did not change total activity, but increased percent three- four-fold 4-6 h. Identical results were observed adrenalectomized rats pretreated one dose alpha-methylprednisolone (2.5 mg/kg i.p.) 30-60 min before saline or injection, indicating that endotoxin's effect mediated hypersecretion adrenal hormones. Cortisone pretreatment normal (100 per d) 2 d prevented endotoxin-induced activation BCKAD, suggesting endogenous secretion products endotoxin. Human recombinant tumor necrosis factor-alpha and/or IL-1 beta alpha (50 micrograms/kg) two- fourfold h after intravenous injection. We conclude cytokine-mediated may contribute septicemia.