Open AccessImoxin attenuates LPS‐induced inflammation and MuRF1 expression in mouse skeletal muscle
Author(s) -
Valentine Rudy J.,
Jefferson Matthew A.,
Kohut Marian L.,
Eo Hyeyoon
Publication year - 2018
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.13941
Subject(s) - skeletal muscle , inflammation , lipopolysaccharide , medicine , endocrinology , protein kinase b , gastrocnemius muscle , muscle atrophy , tumor necrosis factor alpha , in vivo , foxo3 , messenger rna , pi3k/akt/mtor pathway , downregulation and upregulation , proinflammatory cytokine , chemistry , biology , signal transduction , biochemistry , microbiology and biotechnology , gene
The double‐stranded RNA ‐dependent protein kinase ( PKR ) contributes to inflammatory cytokine expression and disease pathogenesis in many conditions. Limited data are available on the efficacy of the PKR inhibitor imoxin to prevent lipopolysaccharide ( LPS )‐induced inflammation in skeletal muscle in vivo. The aim of this study was to evaluate the effect of imoxin, a PKR inhibitor, on inflammatory and atrophy signaling in skeletal muscle in response to an acute inflammatory insult with LPS . Six‐week old C57 BL /6J mice received vehicle (saline) or 0.5 mg/kg imoxin 24 and 2 h prior to induction of inflammation via 1 mg/kg LPS . Gastrocnemius muscles were collected 24 h post‐ LPS and mRNA and protein expression were assessed. LPS lead to a loss of body weight, which was similar in Imoxin+ LPS . There were no differences in muscle weight among groups. LPS increased gastrocnemius mRNA expression of TNF ‐ α and IL ‐1 β , and protein levels of NLRP 3, all of which were attenuated by imoxin. Similarly, IL ‐6 mRNA and IL ‐1 β protein were suppressed in Imoxin+ LPS compared to LPS alone. LPS increased mRNA of the atrogenes, Mu RF 1 and MAF bx, and imoxin attenuated the LPS ‐induced increase in Mu RF 1 mRNA , and lowered Mu RF 1 protein. Imoxin+ LPS increased p‐Akt compared to saline or LPS , whereas p‐ mTOR was unaltered. FoxO1 was upregulated and p‐FoxO1/FoxO1 reduced by LPS , both of which were prevented by imoxin. Both LPS and Imoxin+ LPS had diminished p‐FoxO3/FoxO3 compared to control. These results demonstrate the potential anti‐inflammatory and anti‐atrophy effects of imoxin on skeletal muscle in vivo.