Abstract
Acute treatment of rats with recombinant tumour necrosis factor (TNF-α) caused an enhanced proteolytic rate —measured as tyrosine released in the presence of cycloheximide — insoleus muscle (34%). The cytokine treatment also decreased the rate of protein synthesis in this muscle (22%) while it had no effect upon the same parameter inextensor digitorum longus (EDL) (26%) muscle. In addition, treatment of rats with TNF-α increased amino acid uptake by transport system A in the incubated muscles both insoleus (45%) andEDL (99%) in the presence of insulin in the incubating medium. This effect was not associated with a direct action of TNF on muscle since the addition of different concentrations of the cytokine to the preparations did not alter the uptake of α-(methyl)-aminoisobutyric acid by the incubated muscles. It can be concluded that acute TNF-α treatment causes changes in protein metabolism in red-type muscles — suchsoleus — while little effects are seen in white-type muscles — such as EDL. The results presented may, to some extent, be related to the cachectic response associated with cancer and inflammation.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Beutler B, Cerami A: Tumor necrosis, cachexia, shock, and inflammation: A common mediator. Annu Rev Biochem 57: 505–518, 1988
Strain AJ: Cancer cachexia in man: A review. Invest Cell Pathol 2: 181–193, 1979
Evans RD, Argilés JM, Williamson DH: Metabolic effects of tumour necrosis factor-α (cachectin) and interleukin-1. Clin Sci 77: 357–364, 1989
Goldberg AL, Kettelhut IC, Furono K, Fagan JM, Baracos V: Activation of protein breakdown and prostaglandin E2 production in rat skeletal muscle in fever is signaled by a macrophage product distinct from interleukin-1 or other known monokines. J Clin Invest 81: 1378–1383, 1988
Warren RS, Starnes HF Jr, Gabrilove JL, Oettgen HF, Brennan MF: The acute metabolic effects of tumor necrosis factor administration to human. Arch Surg 122: 1396–1400 1987
Starnes HF Jr, Warren RS, Jeevanandam M, Gabrilove JL, Larchian W, Oettgen HF, Brennan MF: Tumour necrosis factor and the acute metabolic response to tissue injury in man. J Clin Invest 82: 1321–1325, 1988
Fong Y, Moldawer LL, Marano M, Wei H, Barber A, Manogue K, Tracey KJ, Kuo G, Fischman DA, Cerami A, Lowry SF: Cachectin/TNF or IL-1α induces cachexia with redistribution of body proteins. Am J Physiol 256: R659–665, 1989
Charters Y, Grimble RF: Effect of recombinant human tumour necrosis factor α on protein synthesis in liver, skeletal muscle and skin of rats. Biochem J 258: 493–497, 1989
Flores EA, Bistrian BR, Pomposelli JJ, Dinarello CA, Blackburn GL, Istfan NW: Infusion of tumor necrosis factor/cachectin promotes muscle catabolism in the rat. J Clin Invest 83: 1614–1622, 1989
Kettelhut IC, Goldberg AL: Tumor necrosis factor can induce fever in rats without activating protein breakdown in muscle or lipolysis in adipose tissue. J Clin Invest 81: 1384–1389, 1988
Moldawer LL, Svaninger G, Gelin J, Lundholm KG: Interleukin-1 and tumor necrosis factor do not regulate protein balance in skeletal muscle. Am J Physiol 253: C766–773, 1987
Goodman MN: Tumor necrosis factor induces skeletal muscle protein breakdown in rats. Am J Physiol 260: E727–730, 1991
Gumà A, Testar X, Palacín M, Zorzano A: Insulin-stimulated —(methyl)aminoisobutyric acid uptake in skeletal muscle. Biochem J 253: 625–629, 1988
Hohorst HJ: Metabolitgehalte und Metabolitkoncentrationen in der Leber der Ratte. In: HU Bergmeyer (ed.) Methods of Enzymatic Analysis. Academic Press, New York, 1963, pp 215–219
Waalkes TP, Denfriend SU: A fluorometric method for the estimation of tyrosine in plasma and tissues. J Lab Clin Med 50: 733–736, 1957
Argilés JM, López-Soriano FJ, Wiggins D, Williamson DH: Comparative effects of tumour necrosis factor-α (cachectin), interleukin-1β, and tumour growth on amino acid metabolism in the ratin vivo. Biochem J 261: 357–362, 1989
Aggarwal BB, Eessalu TE, Hass PE: Characterization of receptors for human tumor necrosis factor and their regulation by interferon-gamma. Nature 318: 665–667, 1985
Nawroth PP, Bank I, Handley D, Cassimeris J, Chess L, Stern D: Tumor necrosis factor interacts with endothelial cell receptors to induce release of interleukin-1. J Exp Med 163: 1363–1375, 1986
Tracey KL, Wei H, Manogue KR, Fong Y, Hesse DG, Nguyen HT, Kuo GC, Beutler B, Cotran RS, Cerami A, Lowry SF: Cachectin/tumour necrosis factor induces cachexia, anemia and inflammation. J Exp Med 167: 1211–1227, 1988
Baracos V, Rodemann HP, Dinarello CA, Goldberg AL: Stimulation of muscle protein degradation and prostaglandin E2 release by leukocytic pyrogen (interleukin-1) New Engl J Med 308: 553–558, 1983
Clowes GHA, George BC, Villee CA Jr, Saravis CA: Muscle proteolysis induced by a circulating peptide in patients with sepsis of trauma. New Engl J Med 308: 545–552, 1983
Rofe AM, Conyers RAJ, Bais R, Gamble JR, Vadas MA: The effects of recombinant tumour necrosis factor (cachectin) on metabolism in isolated rat adipocyte, hepatocyte and muscle preparations. Biochem J 247: 789–792, 1987
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
García-Martínez, C., López-Soriano, F.J. & Argilés, J.M. Acute treatment with tumour necrosis factor-α induces changes in protein metabolism in rat skeletal muscle. Mol Cell Biochem 125, 11–18 (1993). https://doi.org/10.1007/BF00926829
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00926829