{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T23:06:26Z","timestamp":1788649586067,"version":"build-2803163510"},"reference-count":62,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,12,7]],"date-time":"2017-12-07T00:00:00Z","timestamp":1512604800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P20 RR\u2010017698"],"award-info":[{"award-number":["P20 RR\u2010017698"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 CA\u2010121249"],"award-info":[{"award-number":["R01 CA\u2010121249"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Skeletal muscle responds to eccentric contractions (ECC) with an anabolic response that involves the induction of protein synthesis through the mechanistic target of rapamycin complex 1. While we have reported that repeated ECC bouts after cachexia initiation attenuated muscle mass loss and inflammatory signalling, cachectic muscle's capacity to induce protein synthesis in response to ECC has not been determined. Therefore, we examined cachectic muscle's ability to induce mechano\u2010sensitive pathways and protein synthesis in response to an anabolic stimulus involving ECC and determined the role of muscle signal transducer and activator of transcription 3 (STAT3)\/nuclear factor kappa\u2010light\u2010chain\u2010enhancer of activated B cells (NF\u03baB) signalling on ECC\u2010induced anabolic signalling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Mechano\u2010sensitive pathways and anabolic signalling were examined immediately post or 3\u00a0h after a single ECC bout in cachectic male <jats:italic>Apc<\/jats:italic><jats:sup><jats:italic>Min\/+<\/jats:italic><\/jats:sup> mice (<jats:italic>n<\/jats:italic>\u00a0=\u00a017; 16\u00a0\u00b1\u00a01% body weight loss). Muscle STAT3\/NF\u03baB regulation of basal and ECC\u2010induced anabolic signalling was also examined in an additional cohort of <jats:italic>Apc<\/jats:italic><jats:sup><jats:italic>Min\/+<\/jats:italic><\/jats:sup> mice (<jats:italic>n<\/jats:italic>\u00a0=\u00a010; 16\u00a0\u00b1\u00a01% body weight loss) that received pyrrolidine dithiocarbamate 24\u00a0h prior to a single ECC bout. In all experiments, the left tibialis anterior performed ECC while the right tibialis anterior served as intra\u2010animal control. Data were analysed by Student's <jats:italic>t<\/jats:italic>\u2010test or two\u2010way repeated measures analysis of variance with Student\u2010Newman\u2010Keuls post\u2010hoc when appropriate. The accepted level of significance was set at <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05 for all analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>Apc<\/jats:italic><jats:sup><jats:italic>Min\/+<\/jats:italic><\/jats:sup> mice exhibited a cachectic muscle signature demonstrated by perturbed proteostasis (Ribosomal Protein S6 (RPS6), P70S6K, Atrogin\u20101, and Muscle RING\u2010finger protein\u20101 (MuRF1)), metabolic (adenosine monophosphate\u2010activated protein kinase, Peroxisome proliferator\u2010activated receptor gamma coactivator 1\u2010alpha (PGC\u20101\u03b1), and Cytochrome c oxidase subunit IV (COXIV)), and inflammatory (STAT3, NF\u03baB, extracellular signal\u2010regulated kinases 1 and 2, and P38) signalling pathway regulation. Nonetheless, mechano\u2010sensitive signalling pathways (P38, extracellular signal\u2010regulated kinases 1 and 2, and Protein kinase B (AKT)) were activated immediately post\u2010ECC irrespective of cachexia. While cachexia did not attenuate ECC\u2010induced P70S6K activation, the protein synthesis induction remained suppressed compared with healthy controls. However, muscle STAT3\/NF\u03baB inhibition increased basal and ECC\u2010induced protein synthesis in cachectic <jats:italic>Apc<\/jats:italic><jats:sup><jats:italic>Min\/+<\/jats:italic><\/jats:sup> mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These studies demonstrate that mechano\u2010sensitive signalling is maintained in cachectic skeletal muscle, but chronic STAT3\/NF\u03baB signalling serves to attenuate basal and ECC\u2010induced protein synthesis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.12271","type":"journal-article","created":{"date-parts":[[2017,12,7]],"date-time":"2017-12-07T12:12:52Z","timestamp":1512648772000},"page":"369-383","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Inflammatory signalling regulates eccentric contraction\u2010induced protein synthesis in cachectic skeletal muscle"],"prefix":"10.1002","volume":"9","author":[{"given":"Justin 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University of South Carolina  Columbia SC 29208 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ho\u2010Jin","family":"Koh","sequence":"additional","affiliation":[{"name":"Department of Exercise Science University of South Carolina  Columbia SC 29208 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A.","family":"Carson","sequence":"additional","affiliation":[{"name":"Department of Exercise Science University of South Carolina  Columbia SC 29208 USA"},{"name":"Center for Colon Cancer Research University of South Carolina  Columbia SC 29208 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