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Accordingly, male Sprague-Dawley rats were exposed to an ethanol-containing diet for 16 weeks and compared with a control group that was fed an isocaloric diet. Histological measurements from H&amp;E slides revealed no significant differences in cell size. A proteomic approach revealed that alcohol exposure leads to enhanced mitochondrial lipid metabolism, and electron microscopy revealed impairments in mitochondrial morphology\/density. Cardiac myosin purified from the hearts of ethanol-exposed animals demonstrated a 15% reduction in high-salt ATPase activity, with no significant changes in the in vitro motility and low-salt ATPase or formation of the super-relaxed (SRX) state. A protein carbonyl assay indicated a 20% increase in carbonyl incorporation, suggesting that alcohol may impact cardiac myosin through oxidative stress mechanisms. In vitro oxidation of healthy cardiac myosin revealed a dramatic decline in ATPase activity and in vitro motility, demonstrating a link between myosin protein oxidation and myosin mechanochemistry. Collectively, this study suggests alcohol-induced metabolic remodeling may be the initial insult that eventually leads to defects in the contractile machinery in the myocardium of ACM hearts.<\/jats:p>","DOI":"10.3390\/ijms26146766","type":"journal-article","created":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T11:52:58Z","timestamp":1752580378000},"page":"6766","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Early-Stage Alcoholic Cardiomyopathy Highlighted by Metabolic Remodeling, Oxidative Stress, and Cardiac Myosin Dysfunction in Male Rats"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3891-0694","authenticated-orcid":false,"given":"David V.","family":"Rasicci","sequence":"first","affiliation":[{"name":"Department of Cell and Biological Systems, Penn State College of Medicine, Hershey, PA 17033, USA"},{"name":"Department of Pathology, Anatomy, and Laboratory Medicine, West Virginia University School of Medicine, Morgantown, WV 26505, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5820-1521","authenticated-orcid":false,"given":"Jinghua","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Cell and Biological Systems, Penn State College of Medicine, Hershey, PA 17033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1619-022X","authenticated-orcid":false,"given":"Adrien P.","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cell and Biological Systems, Penn State College of Medicine, Hershey, PA 17033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil B.","family":"Wood","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, VT 05405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5794-6927","authenticated-orcid":false,"given":"Skylar M. L.","family":"Bodt","sequence":"additional","affiliation":[{"name":"Department of Cell and Biological Systems, Penn State College of Medicine, Hershey, PA 17033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allyson L.","family":"Toro","sequence":"additional","affiliation":[{"name":"Department of Cell and Biological Systems, Penn State College of Medicine, Hershey, PA 17033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Evans","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Experimental Therapeutics, Penn State College of Medicine, Hershey, PA 17033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omid","family":"Golestanian","sequence":"additional","affiliation":[{"name":"Department of Pathology, Anatomy, and Laboratory Medicine, West Virginia University School of Medicine, Morgantown, WV 26505, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md Shahrier","family":"Amin","sequence":"additional","affiliation":[{"name":"Department of Pathology, Anatomy, and Laboratory Medicine, West Virginia University School of Medicine, Morgantown, WV 26505, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Pruznak","sequence":"additional","affiliation":[{"name":"Department of Cell and Biological Systems, Penn State College of Medicine, Hershey, PA 17033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelli","family":"Mnatsakanyan","sequence":"additional","affiliation":[{"name":"Department of Cell and Biological Systems, Penn State College of Medicine, Hershey, PA 17033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4694-4053","authenticated-orcid":false,"given":"Yuval","family":"Silberman","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Experimental Therapeutics, Penn State College of Medicine, Hershey, PA 17033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0645-6864","authenticated-orcid":false,"given":"Michael D.","family":"Dennis","sequence":"additional","affiliation":[{"name":"Department of Cell and Biological Systems, Penn State College of Medicine, Hershey, PA 17033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Previs","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, VT 05405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles H.","family":"Lang","sequence":"additional","affiliation":[{"name":"Department of Cell and Biological Systems, Penn State College of Medicine, Hershey, PA 17033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher M.","family":"Yengo","sequence":"additional","affiliation":[{"name":"Department of Cell and Biological Systems, Penn State College of Medicine, Hershey, PA 17033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2223","DOI":"10.1016\/S0140-6736(09)60746-7","article-title":"Global burden of disease and injury and economic cost attributable to alcohol use and alcohol-use disorders","volume":"373","author":"Rehm","year":"2009","journal-title":"Lancet"},{"key":"ref_2","first-page":"35","article-title":"Social and Cultural Contexts of Alcohol Use: Influences in a Social-Ecological Framework","volume":"38","author":"Sudhinaraset","year":"2016","journal-title":"Alcohol Res."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Roerecke, M. 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