{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T21:35:57Z","timestamp":1791668157844,"version":"4.3.4"},"reference-count":43,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2024,8,21]],"date-time":"2024-08-21T00:00:00Z","timestamp":1724198400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007434","name":"Suzuken Memorial Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007434","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008731","name":"Nakatomi Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>Oxidative stress contributes to the loss of skeletal muscle mass and function in cancer cachexia. However, this outcome may be mitigated by an improved endogenous antioxidant defence system. Here, using the well\u2010established oxidative stress\u2010inducing muscle atrophy model of Lewis lung carcinoma (LLC) in 13\u2010week\u2010old male C57BL\/6J mice, we demonstrate that extracellular superoxide dismutase (EcSOD) levels increase in the cachexia\u2010prone extensor digitorum longus muscle. LLC transplantation significantly increased interleukin\u20101\u03b2 (IL\u20101\u03b2) expression and release from extensor digitorum longus muscle fibres. Moreover, IL\u20101\u03b2 treatment of C2C12 myotubes increased NBR1, p62 phosphorylation at Ser351, Nrf2 nuclear translocation and EcSOD protein expression. Additional studies <jats:italic>in vivo<\/jats:italic> indicated that intramuscular IL\u20101\u03b2 injection is sufficient to stimulate EcSOD expression, which is prevented by muscle\u2010specific knockout of p62 and Nrf2 (i.e. in p62 skmKO and Nrf2 skmKO mice, respectively). Finally, since an increase in circulating IL\u20101\u03b2 may lead to unwanted outcomes, we demonstrate that targeting this pathway at p62 is sufficient to drive muscle EcSOD expression in an Nrf2\u2010dependent manner. In summary, cancer cachexia increases EcSOD expression in extensor digitorum longus muscle via muscle\u2010derived IL\u20101\u03b2\u2010induced upregulation of p62 phosphorylation and Nrf2 activation. These findings provide further mechanistic evidence for the therapeutic potential of p62 and Nrf2 to mitigate cancer cachexia\u2010induced muscle atrophy.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp16249-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Oxidative stress plays an important role in muscle atrophy during cancer cachexia.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>EcSOD, which mitigates muscle loss during oxidative stress, is upregulated in 13\u2010week\u2010old male C57BL\/6J mice of extensor digitorum longus muscles during cancer cachexia.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Using mouse and cellular models, we demonstrate that cancer cachexia promotes muscle EcSOD protein expression via muscle\u2010derived IL\u20101\u03b2\u2010dependent stimulation of the NBR1\u2010p62\u2010Nrf2 signalling pathway.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These results provide further evidence for the potential therapeutic targeting of the NBR1\u2010p62\u2010Nrf2 signalling pathway downstream of IL\u20101\u03b2 to mitigate cancer cachexia\u2010induced muscle atrophy.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp286460","type":"journal-article","created":{"date-parts":[[2024,8,21]],"date-time":"2024-08-21T23:28:06Z","timestamp":1724282886000},"page":"4215-4235","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Muscle\u2010derived IL\u20101\u03b2 regulates EcSOD expression via the NBR1\u2010p62\u2010Nrf2 pathway in muscle during cancer cachexia"],"prefix":"10.1113","volume":"602","author":[{"given":"Mami","family":"Yamada","sequence":"first","affiliation":[{"name":"Graduate School of Science Nagoya City University  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiji","family":"Warabi","sequence":"additional","affiliation":[{"name":"Institute of Medicine University of Tsukuba  Tsukuba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisashi","family":"Oishi","sequence":"additional","affiliation":[{"name":"Department of Comparative and Experimental Medicine Nagoya City University Graduate School of Medical Sciences  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3162-3804","authenticated-orcid":false,"given":"Vitor A.","family":"Lira","sequence":"additional","affiliation":[{"name":"Department of Health &amp; Human Physiology, Fraternal Order of Eagles Diabetes Research Center, Abboud Cardiovascular Research Center, Obesity Research and Education Initiative, Pappajohn Biomedical Institute The University of Iowa  Iowa City Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3787-5594","authenticated-orcid":false,"given":"Mitsuharu","family":"Okutsu","sequence":"additional","affiliation":[{"name":"Graduate School of Science Nagoya City University  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,8,21]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00248.2004"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202100263R"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3829"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00099-20"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.105"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1526-968X(200002)26:2<165::AID-GENE22>3.0.CO;2-F"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12615"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12354"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12232"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.114.001540"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.24.19.8477-8486.2004"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(10)70218-7"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2012.06.011"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP270818"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2954-12.2013"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.7.3.14487"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.13540"},{"issue":"9","key":"e_1_2_5_19_1","article-title":"TAK1 converts Sequestosome 1\/p62 from an autophagy receptor to a signaling platform","volume":"20","author":"Kehl S. 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