TNF-binding protein ameliorates inhibition  of skeletal muscle protein synthesis during sepsis

Cooney, Robert N.; Kimball, Scot R.; Eckman, R. A.; Maish, George O.; Shumate, Margaret L.; Vary, Thomas C.

doi:10.1152/ajpendo.1999.276.4.e611

Cited by 44 publications

(69 citation statements)

References 29 publications

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“…The decrease in body weight in arthritic rats can be seen in the decrease in skeletal muscle weight and in the adipose mass. This muscular atrophy has been reported in adjuvant-arthritic rats (Hamada et al 2000), septic rats (Cooney et al 1999) and rats treated with TNF (Hoshino et al 1991). In TNF-infused rats, the loss of gastrocnemius mass has been ascribed to food intake reduction (Hoshino et al 1991).…”

Section: Discussionmentioning

confidence: 75%

“…PEG-sTNFRI administration did not change gastrocnemius weight in control or in arthritic rats. Similarly, administration of this TNF-a inhibitory protein did not modify gastrocnemius weight in control rats, although this inhibitory protein increased it in septic rats (Cooney et al 1999). The increase in body weight gain in arthritic rats after PEG-sTNFRI administration is reflected in the increase in fat mass.…”

Section: Discussionmentioning

confidence: 80%

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Tumour necrosis factor blockade did not prevent the increase of muscular muscle RING finger-1 and muscle atrophy F-box in arthritic rats

Granado¹,

Martín²,

Priego³

et al. 2006

Journal of Endocrinology

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Chronic inflammation is associated with a decrease in body weight and cachexia, which is characterized by anorexia and skeletal muscle wasting. The expression of atrogens muscle RING finger-1 (MuRF-1) and muscle atrophy F-box (MAFbx) are increased in muscle atrophy and it is known that tumour necrosis factor (TNF) regulates skeletal muscle loss through TNF receptor p55 (TNFRI). The aim of this study was to examine the effect of polyethylene glycol linked to soluble TNFRI (PEG-sTNFRI) on gene expression of the atrogens MuRF-1 and MAFbx in skeletal muscle of arthritic rats. Rats were injected with Freund's adjuvant and, 15 days later, arthritic and control rats were injected daily with PEG-sTNFRI (1 mg/kg, s.c.) or saline for 8 days. Arthritis decreased body weight gain, the weight of skeletal muscle and adipose mass. PEG-sTNFRI administration increased body weight gain and adipose mass of arthritic rats; however, it did not modify the skeletal muscle weight. The gene expression of TNF-a, MuRF1 and MAFbx, IGF-I and IGFBP-5 were increased in the skeletal muscle of arthritic rats, and the administration of PEG-sTNFRI did not modify these parameters. These data suggest that the anti-TNF agent PEG-sTNFRI did not prevent the increase in E3 ubiquitinligating enzymes, MuRF1 and MAFbx, gene expression in the skeletal muscle of arthritic rats.

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Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 80%

Tumour necrosis factor blockade did not prevent the increase of muscular muscle RING finger-1 and muscle atrophy F-box in arthritic rats

Granado¹,

Martín²,

Priego³

et al. 2006

Journal of Endocrinology

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“…In previous studies, treatment of septic rats with agents which decrease TNFα synthesis or antagonize its actions prevented the decrease in protein synthesis and translation initiation as well as the accompanying loss of muscle protein (36,37). These data are consistent with the ability of a sustained infusion of recombinant TNFα to decrease basal peptide-chain initiation and protein synthesis in fasted rats (20).…”

Section: Discussionmentioning

confidence: 94%

“…This sepsisinduced leucine resistance appears independent of changes in translation initiation mediated by the eIF2/eIF2B system. However, we cannot exclude the potential importance of this system in more chronic (for example, 5 days) septic models where eIF2Bε has been shown to be reduced (36).…”

Section: Discussionmentioning

confidence: 98%

Glucocorticoids and TNFα Interact Cooperatively to Mediate Sepsis-Induced Leucine Resistance in Skeletal Muscle

Lang

Frost

2006

Mol Med

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Sepsis blunts the ability of nutrient signaling by leucine to stimulate skeletal muscle protein synthesis by impairing translation initiation. The present study tested the hypothesis that overproduction of either tumor necrosis factor (TNF)-α or glucocorticoids mediate the sepsis-induced leucine resistance. Prior to producing peritonitis, rats received either vehicle, TNF binding protein (TNF BP ) to inhibit endogenous TNFα action, and/or the glucocorticoid receptor antagonist RU486. Leucine was orally administered to all rats 24 h thereafter and the gastrocnemius removed 20 min later to assess protein synthesis and signaling components important in controlling peptide-chain initiation. Muscle protein synthesis was 65% lower in septic rats administered leucine than in leucinetreated control animals. This reduction was not prevented by either TNF BP or RU486 alone, but was completely reversed by the combination. This sepsis-induced leucine resistance was associated with an 80% reduction in the amount of active eIF4E·eIF4G complex, a 5-fold increase in the formation of the inactive eIF4E·4E-BP1 complex as well as markedly reduced (at least 70%) phosphorylation of 4E-BP1, eIF4G, S6K1, S6, and mTOR. Pretreatment of septic rats with either TNF BP or RU486 individually only nominally improved the leucine action as assessed by the above-mentioned endpoints. In contrast, when TNF BP and RU486 were co-administered, the ability of sepsis to impair the leucine-stimulated phosphorylation of 4E-BP1, eIF4G, S6K1, and S6 as well as the redistribution of eIF4E was essentially prevented. No differences in the total amount or phosphorylation of eIF2α and eIF2Bε were detected between the different groups, and changes could not be attributed to differences in the prevailing plasma concentration of insulin or leucine. Our data demonstrate the sepsis-induced leucine resistance in skeletal muscle results from the cooperative interaction of both TNFα and glucocorticoids.

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“…kines, because infusion of cytokines and dexamethasone in rats induced changes in IGF-I and its binding proteins similar to that of burn injury, while their antagonists or binding proteins attenuated these changes in burn models (e.g., 7,11,42,43,49). It appears therefore that normalization of glucocorticoid and proinflammatory cytokine responses by ghrelin may, at least in part, contribute to its ability to attenuate burn-induced changes in the mRNA expression of IGF-I and its binding proteins in liver and skeletal muscle.…”

Section: Discussionmentioning

confidence: 99%

Ghrelin inhibits skeletal muscle protein breakdown in rats with thermal injury through normalizing elevated expression of E3 ubiquitin ligases MuRF1 and MAFbx

Balasubramaniam

Joshi²,

Su³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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Balasubramaniam A, Joshi R, Su C, Friend LA, Sheriff S, Kagan RJ, James JH. Ghrelin inhibits skeletal muscle protein breakdown in rats with thermal injury through normalizing elevated expression of E3 ubiquitin ligases MuRF1 and MAFbx. Am J Physiol Regul Integr Comp Physiol 296: R893-R901, 2009. First published February 11, 2009; doi:10.1152/ajpregu.00015.2008.-We previously determined that ghrelin synthesis was downregulated after burn injury and that exogenous ghrelin retained its ability both to stimulate food intake and to restore plasma growth hormone levels in burned rats. These observations and the finding that anabolic hormones can attenuate skeletal muscle catabolism led us to investigate whether ghrelin could attenuate burn-induced skeletal muscle protein breakdown in rats. These studies were performed in young rats (50 -60 g) 24 h after ϳ30% total body surface area burn injury. Burn injury increased total and myofibrillar protein breakdown in extensor digitorum longus (EDL) muscles assessed by in vitro tyrosine and 3-methyl-histidine release, respectively. Continuous 24-h administration of ghrelin (0.2 mg ⅐ kg Ϫ1 ⅐ h Ϫ1 ) significantly inhibited both total and myofibrillar protein breakdown in burned rats. Ghrelin significantly attenuated burninduced changes in mRNA expression of IGFBP-1 and IGFBP-3 in liver. In EDL, ghrelin attenuated the increases in mRNA expression of the binding proteins, but had no significant effect on reduced expression of IGF-I. Ghrelin markedly reduced the elevated mRNA expression of TNF-␣ and IL-6 in EDL muscle that occurred after burn. Moreover, ghrelin normalized plasma glucocorticoid levels, which were elevated after burn. Expression of the muscle-specific ubiquitinligating enzyme (E3) ubiquitin ligases MuRF1 and MAFbx were markedly elevated in both EDL and gastrocnemius and were normalized by ghrelin. These results suggest that ghrelin is a powerful anticatabolic compound that reduces skeletal muscle protein breakdown through attenuating multiple burn-induced abnormalities.

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TNF-binding protein ameliorates inhibition of skeletal muscle protein synthesis during sepsis

Cited by 44 publications

References 29 publications

Tumour necrosis factor blockade did not prevent the increase of muscular muscle RING finger-1 and muscle atrophy F-box in arthritic rats

Tumour necrosis factor blockade did not prevent the increase of muscular muscle RING finger-1 and muscle atrophy F-box in arthritic rats

Glucocorticoids and TNFα Interact Cooperatively to Mediate Sepsis-Induced Leucine Resistance in Skeletal Muscle

Ghrelin inhibits skeletal muscle protein breakdown in rats with thermal injury through normalizing elevated expression of E3 ubiquitin ligases MuRF1 and MAFbx

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