Mechanism of IL-1 induced inhibition of protein synthesis in skeletal muscle

Robert N. Cooney, George O. Maish, Tracie Gilpin, Margaret L. Shumate, Charles H. Lang, Thomas C. Vary

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Chronic interleukin (IL)-1 administration is associated with negative nitrogen balance and the loss of lean body mass. To elucidate the molecular mechanism(s) by which IL-1 modulates protein metabolism in muscle, we investigated the effects of chronic (6 day) IL-1α infusion on protein synthesis in individual muscles (gastrocnemius, soleus, heart) compared with saline-infused control rats. IL-1 significantly decreased muscle weight, protein content, and the rate of protein synthesis in gastrocnemius (fast-twitch muscle). IL-1 had no effect on these parameters in the heart, whereas only the rate of protein synthesis was reduced in soleus (slow-twitch muscle). The reduction in gastrocnemius protein synthesis was not the result of a decrease in total RNA content, but was associated with a diminished translational efficiency. The diminished translational efficiency correlated with a 40% reduction in the ∈-subunit of eukaryotic initiation factor 2B (elF2B∈) in gastrocnemius from IL-1-treated animals. However, the content of the α-subunit of elF2 (elF2α) was unaffected. In contrast, the elF2α content in heart was increased by IL-1, although elF2B∈ levels were unchanged. Reductions in skeletal muscle protein synthesis were not associated with a concomitant reduction in circulating or tissue content of insulin-like growth factor I. In summary, the IL-1-induced decrease in gastrocnemius protein synthesis appears to be regulated at the level of RNA translation via a reduction in elF2B∈. These findings support a regulatory role for IL-1 as a mediator of muscle protein synthesis and the alterations in body composition observed in catabolic states where this cytokine is overexpressed.

Original languageEnglish (US)
Pages (from-to)235-241
Number of pages7
JournalShock
Volume11
Issue number4
DOIs
StatePublished - Apr 1999

Fingerprint

Interleukin-1
Skeletal Muscle
Proteins
Muscle Proteins
Muscles
Eukaryotic Initiation Factor-2B
RNA
Body Composition
Insulin-Like Growth Factor I
Nitrogen
Cytokines
Weights and Measures

All Science Journal Classification (ASJC) codes

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Cooney, R. N., Maish, G. O., Gilpin, T., Shumate, M. L., Lang, C. H., & Vary, T. C. (1999). Mechanism of IL-1 induced inhibition of protein synthesis in skeletal muscle. Shock, 11(4), 235-241. https://doi.org/10.1097/00024382-199904000-00002
Cooney, Robert N. ; Maish, George O. ; Gilpin, Tracie ; Shumate, Margaret L. ; Lang, Charles H. ; Vary, Thomas C. / Mechanism of IL-1 induced inhibition of protein synthesis in skeletal muscle. In: Shock. 1999 ; Vol. 11, No. 4. pp. 235-241.
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Cooney, RN, Maish, GO, Gilpin, T, Shumate, ML, Lang, CH & Vary, TC 1999, 'Mechanism of IL-1 induced inhibition of protein synthesis in skeletal muscle', Shock, vol. 11, no. 4, pp. 235-241. https://doi.org/10.1097/00024382-199904000-00002

Mechanism of IL-1 induced inhibition of protein synthesis in skeletal muscle. / Cooney, Robert N.; Maish, George O.; Gilpin, Tracie; Shumate, Margaret L.; Lang, Charles H.; Vary, Thomas C.

In: Shock, Vol. 11, No. 4, 04.1999, p. 235-241.

Research output: Contribution to journalArticle

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T1 - Mechanism of IL-1 induced inhibition of protein synthesis in skeletal muscle

AU - Cooney, Robert N.

AU - Maish, George O.

AU - Gilpin, Tracie

AU - Shumate, Margaret L.

AU - Lang, Charles H.

AU - Vary, Thomas C.

PY - 1999/4

Y1 - 1999/4

N2 - Chronic interleukin (IL)-1 administration is associated with negative nitrogen balance and the loss of lean body mass. To elucidate the molecular mechanism(s) by which IL-1 modulates protein metabolism in muscle, we investigated the effects of chronic (6 day) IL-1α infusion on protein synthesis in individual muscles (gastrocnemius, soleus, heart) compared with saline-infused control rats. IL-1 significantly decreased muscle weight, protein content, and the rate of protein synthesis in gastrocnemius (fast-twitch muscle). IL-1 had no effect on these parameters in the heart, whereas only the rate of protein synthesis was reduced in soleus (slow-twitch muscle). The reduction in gastrocnemius protein synthesis was not the result of a decrease in total RNA content, but was associated with a diminished translational efficiency. The diminished translational efficiency correlated with a 40% reduction in the ∈-subunit of eukaryotic initiation factor 2B (elF2B∈) in gastrocnemius from IL-1-treated animals. However, the content of the α-subunit of elF2 (elF2α) was unaffected. In contrast, the elF2α content in heart was increased by IL-1, although elF2B∈ levels were unchanged. Reductions in skeletal muscle protein synthesis were not associated with a concomitant reduction in circulating or tissue content of insulin-like growth factor I. In summary, the IL-1-induced decrease in gastrocnemius protein synthesis appears to be regulated at the level of RNA translation via a reduction in elF2B∈. These findings support a regulatory role for IL-1 as a mediator of muscle protein synthesis and the alterations in body composition observed in catabolic states where this cytokine is overexpressed.

AB - Chronic interleukin (IL)-1 administration is associated with negative nitrogen balance and the loss of lean body mass. To elucidate the molecular mechanism(s) by which IL-1 modulates protein metabolism in muscle, we investigated the effects of chronic (6 day) IL-1α infusion on protein synthesis in individual muscles (gastrocnemius, soleus, heart) compared with saline-infused control rats. IL-1 significantly decreased muscle weight, protein content, and the rate of protein synthesis in gastrocnemius (fast-twitch muscle). IL-1 had no effect on these parameters in the heart, whereas only the rate of protein synthesis was reduced in soleus (slow-twitch muscle). The reduction in gastrocnemius protein synthesis was not the result of a decrease in total RNA content, but was associated with a diminished translational efficiency. The diminished translational efficiency correlated with a 40% reduction in the ∈-subunit of eukaryotic initiation factor 2B (elF2B∈) in gastrocnemius from IL-1-treated animals. However, the content of the α-subunit of elF2 (elF2α) was unaffected. In contrast, the elF2α content in heart was increased by IL-1, although elF2B∈ levels were unchanged. Reductions in skeletal muscle protein synthesis were not associated with a concomitant reduction in circulating or tissue content of insulin-like growth factor I. In summary, the IL-1-induced decrease in gastrocnemius protein synthesis appears to be regulated at the level of RNA translation via a reduction in elF2B∈. These findings support a regulatory role for IL-1 as a mediator of muscle protein synthesis and the alterations in body composition observed in catabolic states where this cytokine is overexpressed.

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