Temporal study following burn injury in young rats is associated with skeletal muscle atrophy, inflammation and altered myogenic regulatory factors

Quintana, Hananiah Tardivo; Bortolin, Jeferson André; Silva, Nathalia Trasmonte da; Ribeiro, Flávia Andressa Pidone; Liberti, Édson Aparecido; Ribeiro, Daniel Araki; Oliveira, Flávia de

doi:10.1007/s00011-014-0783-8

Cited by 27 publications

(36 citation statements)

References 28 publications

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“…Regarding the downstream genes of NF-κB, including TNF-α, IL-1β and iNOS, our findings are consistent with previous studies that burn injury increases these pro-inflammatory genes in skeletal muscle [13, 25, 44–47]. Previous studies have shown that TNF-α and IL-1β proteins are expressed in human and rodent skeletal muscle cells both under normal and disease conditions [48–51] and that iNOS protein is induced in mouse skeletal muscle after LPS injection [52, 53] and burn injury [13].…”

Section: Discussionsupporting

confidence: 92%

iNOS as a Driver of Inflammation and Apoptosis in Mouse Skeletal Muscle after Burn Injury: Possible Involvement of Sirt1 S-Nitrosylation-Mediated Acetylation of p65 NF-κB and p53

et al. 2017

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Inflammation and apoptosis develop in skeletal muscle after major trauma, including burn injury, and play a pivotal role in insulin resistance and muscle wasting. We and others have shown that inducible nitric oxide synthase (iNOS), a major mediator of inflammation, plays an important role in stress (e.g., burn)-induced insulin resistance. However, it remains to be determined how iNOS induces insulin resistance. Moreover, the interrelation between inflammatory response and apoptosis is poorly understood, although they often develop simultaneously. Nuclear factor (NF)-κB and p53 are key regulators of inflammation and apoptosis, respectively. Sirt1 inhibits p65 NF-κB and p53 by deacetylating these transcription factors. Recently, we have shown that iNOS induces S-nitrosylation of Sirt1, which inactivates Sirt1 and thereby increases acetylation and activity of p65 NF-κB and p53 in various cell types, including skeletal muscle cells. Here, we show that iNOS enhances burn-induced inflammatory response and apoptotic change in mouse skeletal muscle along with S-nitrosylation of Sirt1. Burn injury induced robust expression of iNOS in skeletal muscle and gene disruption of iNOS significantly inhibited burn-induced increases in inflammatory gene expression and apoptotic change. In parallel, burn increased Sirt1 S-nitrosylation and acetylation and DNA-binding capacity of p65 NF-κB and p53, all of which were reversed or ameliorated by iNOS deficiency. These results indicate that iNOS functions not only as a downstream effector but also as an upstream enhancer of burn-induced inflammatory response, at least in part, by Sirt1 S-nitrosylation-dependent activation (acetylation) of p65 NF-κB. Our data suggest that Sirt1 S-nitrosylation may play a role in iNOS-mediated enhanced inflammatory response and apoptotic change, which, in turn, contribute to muscle wasting and supposedly to insulin resistance after burn injury.

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Section: Discussionsupporting

confidence: 92%

iNOS as a Driver of Inflammation and Apoptosis in Mouse Skeletal Muscle after Burn Injury: Possible Involvement of Sirt1 S-Nitrosylation-Mediated Acetylation of p65 NF-κB and p53

et al. 2017

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“…Upregulation of MyoD and myogenin together with an increase in inflammatory markers has also been reported in burn-induced muscle atrophy (53). Moreover, collagen-induced arthritis and immobilization increase muscle proteolysis and decrease muscle mass (15).…”

Section: Discussionmentioning

confidence: 96%

Formoterol decreases muscle wasting as well as inflammation in the rat model of rheumatoid arthritis

Gómez-SanMiguel

Gómez-Moreira

Nieto-Bona

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

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Adjuvant-induced arthritis is an experimental model of rheumatoid arthritis that is associated with body weight loss and muscle wasting. β2-adrenergic receptor agonists are powerful anabolic agents that trigger skeletal muscle hypertrophy and have been proposed as a promising treatment for muscle wasting in human patients. The aim of this work was to determine whether formoterol, a selective β2-adrenoreceptor agonist, is able to ameliorate muscle wasting in arthritic rats. Arthritis was induced in male Wistar rats by intradermal injection of Freund's adjuvant. Control and arthritic rats were injected daily with 50 μg/kg sc formoterol or saline for 12 days. Body weight change, food intake, and arthritis index were analyzed. After euthanasia, in the gastrocnemius mRNA was analyzed by PCR, and proteins were analyzed by Western blotting. Arthritis decreased gastrocnemius weight, cross-sectional area, and myofiber size, whereas formoterol increased those variables in both arthritic and control rats. Formoterol decreased the external signs of arthritis as well as NF-κB(p65) activation, TNFα, and COX-2 levels in the gastrocnemius of arthritic and control rats. Those effects of formoterol were associated with a decreased expression of myostatin, atrogin-1, and MuRF1 and in LC3b lipidation. Arthritis increased the expression of MyoD, myogenin, IGF-I, and IGFBP-3 and -5 in the gastrocnemius. In control and in arthritic rats, treatment with formoterol increased Akt phosphorylation and myogenin levels, whereas it decreased IGFBP-3 expression in the gastrocnemius. These data suggest that formoterol has an anti-inflammatory effect and decreases muscle wasting in arthritic rats through increasing Akt activity and myogenin and decreasing myostatin, the p-NF-κB(p65)/TNF pathway, and IGFBP-3.

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“…Myogenesis after burn is not compensatory to cell loss leading to atrophy (10). Myogenesis is dependent on muscle progenitor satellite cells.…”

Section: Introductionmentioning

confidence: 99%

Severe burn increased skeletal muscle loss in mdx mutant mice

Saeman

DeSpain

Liu

et al. 2016

Journal of Surgical Research

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Background-Severe burn causes muscle mass loss and atrophy. The balance between muscle cell death and growth maintains tissue homeostasis. We hypothesize that pre-existing cellular structural defects will exacerbate skeletal muscle mass loss after burn. Using a Duchenne muscular dystrophy (mdx) mutant mouse, we investigated whether severe burn caused more damage in skeletal muscle with pre-existing muscle disease.Methods-The mdx mice and wild type mice received 25% total body surface area (TBSA) scald burn. Gastrocnemius, tibialis anterior, and gluteus muscles were obtained at day 1 and 3 after burn. Gastrocnemius muscle function was measured on day 3. Animals without burn served as controls.Results-Wet tissue weight significantly decreased in tibialis anterior and gluteus in both mdx and wild type mice after burn (p<0.05). The ratio of muscle-to-body weight decreased in mdx mutant mice (p<0.05) but not wild type. Isometric force was significantly lower in mdx gastrocnemius and this difference persisted after burn (p<0.05). Caspase-3 activity increased significantly after burn in both groups, while HMGB1 expression was higher in burn mdx mice (p<0.05). Proliferating cell nuclear antigen (PCNA) decreased significantly in mdx mice (p<0.05).Myogenic markers pax7, myoD and myogenin increased after burn in both groups, and were higher in mdx mice (p<0.05).Conclusion-More muscle loss occurred in response to severe burn in mdx mutant mice. Cell turnover in mdx mice after burn is differed from wild type. Although markers of myogenic activation are elevated in mdx mutant mice, the underlying muscle pathophysiology is less tolerant of traumatic injury.

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Temporal study following burn injury in young rats is associated with skeletal muscle atrophy, inflammation and altered myogenic regulatory factors

Abstract: In conclusion, BI causes inflammation, atrophy and myogenesis stimulation in muscle as a result of systemic host response.

Cited by 27 publications

References 28 publications

iNOS as a Driver of Inflammation and Apoptosis in Mouse Skeletal Muscle after Burn Injury: Possible Involvement of Sirt1 S-Nitrosylation-Mediated Acetylation of p65 NF-κB and p53

iNOS as a Driver of Inflammation and Apoptosis in Mouse Skeletal Muscle after Burn Injury: Possible Involvement of Sirt1 S-Nitrosylation-Mediated Acetylation of p65 NF-κB and p53

Formoterol decreases muscle wasting as well as inflammation in the rat model of rheumatoid arthritis

Severe burn increased skeletal muscle loss in mdx mutant mice

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