{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T08:51:11Z","timestamp":1777884671272,"version":"3.51.4"},"reference-count":37,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T00:00:00Z","timestamp":1749772800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T00:00:00Z","timestamp":1749772800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP23K09768"],"award-info":[{"award-number":["JP23K09768"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alcohol, Clinical and Experimental Research"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chronic alcohol intake induces atrophy of type II (anaerobic, fast\u2010twitch) muscle fibers in preference to type I (aerobic, slow\u2010twitch) muscle fibers. However, the molecular mechanism underlying the preferential atrophy of type II muscle fibers remains unclear. The ubiquitin\u2010proteasome system (UPS) mediates the degradation of myofibrillar proteins in skeletal muscle loss. This study investigated whether E3 ubiquitin ligases, including UBR2 and MuRF1, are involved in ethanol\u2010induced type II muscle fiber\u2010specific atrophy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In a chronic alcohol intake rat model, 4\u2010 to 5\u2010week\u2010old male Wistar rats were fed the Lieber\u2010DeCarli liquid diet for 8\u2009weeks. Muscle specimens were collected from the extensor digitorum longus (EDL) and soleus muscles of both legs. In an in\u00a0vitro model, myotubes differentiated from murine C2C12 myoblasts were treated with culture medium containing 100\u2009mM ethanol or 1\u2009mM acetaldehyde for 6\u2009h.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The muscle weight of the EDL seemed to be lesser in the ethanol group compared to the control group, and there was no difference in the muscle weight of the soleus between these groups. Cross\u2010sectional area (CSA) of type IIA, IIB, and IIX muscle fibers in the EDL of ethanol\u2010fed rats was smaller compared to the control rats, and CSA of type I muscle fibers in the soleus was larger in ethanol\u2010fed rats. UBR2 protein levels seem to increase in the EDL but not in the soleus, whereas MuRF1 protein level remained unchanged in both muscles. C2C12 myotubes expressing MHC IIb, characteristics of type IIB muscle fibers, showed reduced myotube diameter after ethanol or acetaldehyde treatment. Acetaldehyde treatment increased UBR2 expression, but not MuRF1 expression, and enhanced ubiquitination. Knockdown of UBR2 using siRNA prevented acetaldehyde\u2010induced myotube atrophy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study demonstrated that the E3 ligase UBR2 may play a role in alcohol\u2010induced type II muscle\u2010preferential atrophy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/acer.70102","type":"journal-article","created":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T08:31:05Z","timestamp":1749803465000},"page":"1667-1677","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Upregulation of\n                    <scp>E<\/scp>\n                    3 ligase\n                    <scp>UBR<\/scp>\n                    2 in acetaldehyde\u2010treated\n                    <scp>C<\/scp>\n                    2\n                    <scp>C<\/scp>\n                    12 myotubes and its potential involvement in fast\u2010twitch muscle atrophy in alcohol\u2010fed rats"],"prefix":"10.1111","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6363-0964","authenticated-orcid":false,"given":"Kaori","family":"Shintani\u2010Ishida","sequence":"first","affiliation":[{"name":"Department of Forensic Medicine, Graduate School of Medical Science Kyoto Prefectural University of Medicine  Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Ikegaya","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine, Graduate School of Medical Science Kyoto Prefectural University of Medicine  Kyoto 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