A1 Refereed original research article in a scientific journal

Muscle NAD+ depletion and Serpina3n as molecular determinants of murine cancer cachexia—the effects of blocking myostatin and activins




AuthorsHulmi JJ, Penna F, Pöllänen N, Nissinen TA, Hentilä J, Euro L, Lautaoja JH, Ballarò R, Soliymani R, Baumann M, Ritvos O, Pirinen E, Lalowski M

Publication year2020

JournalMolecular Metabolism

Journal name in sourceMolecular metabolism

Journal acronymMol Metab

Article number101046

Volume41

Number of pages13

ISSN2212-8778

eISSN2212-8778

DOIhttps://doi.org/10.1016/j.molmet.2020.101046


Abstract
and Nrk2, as well as decreased muscle protein synthesis. These results indicate putative new treatment therapies for cachexia and that although acute phase protein Serpina3n may serve as a predictor of cachexia, it more likely reflects a condition of elevated inflammation.\n metabolism and protein synthesis were rescued by treatment with sACVR. Across the whole proteome and APR, in particular, Serpina3n represented the most upregulated protein and the strongest predictor of cachexia. However, the increase in Serpina3n expression was associated with increased inflammation rather than decreased muscle mass and/or protein synthesis.\nCancer cachexia and muscle loss are associated with increased morbidity and mortality. In preclinical animal models, blocking activin receptor (ACVR) ligands has improved survival and prevented muscle wasting in cancer cachexia without an effect on tumour growth. However, the underlying mechanisms are poorly understood. This study aimed to identify cancer cachexia and soluble ACVR (sACVR) administration-evoked changes in muscle proteome.\n) metabolism. To complement the first prophylactic experiment, sACVR (or PBS) was injected as a treatment after tumour cell inoculation.\nCONCLUSIONS\nRESULTS\nOBJECTIVE\nMETHODS



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