{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T07:28:20Z","timestamp":1790148500352,"version":"4.0.1"},"reference-count":40,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2019,12,17]],"date-time":"2019-12-17T00:00:00Z","timestamp":1576540800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Dilated (DCM) and ischemic cardiomyopathies (ICM) are associated with cardiac remodeling, where the ubiquitin\u2013proteasome system (UPS) holds a central role. Little is known about the UPS and its alterations in patients suffering from DCM or ICM. The aim of this study is to characterize the UPS activity in human heart tissue from cardiomyopathy patients. Myocardial tissue from ICM (n = 23), DCM (n = 28), and control (n = 14) patients were used to quantify ubiquitinylated proteins, E3-ubiquitin-ligases muscle-atrophy-F-box (MAFbx)\/atrogin-1, muscle-RING-finger-1 (MuRF1), and eukaryotic-translation-initiation-factor-4E (eIF4E), by Western blot. Furthermore, the proteasomal chymotrypsin-like and trypsin-like peptidase activities were determined fluorometrically. Enzyme activity of NAD(P)H oxidase was assessed as an index of reactive oxygen species production. The chymotrypsin- (p = 0.71) and caspase-like proteasomal activity (p = 0.93) was similar between the groups. Trypsin-like proteasomal activity was lower in ICM (0.78 \u00b1 0.11 \u00b5U\/mg) compared to DCM (1.06 \u00b1 0.08 \u00b5U\/mg) and control (1.00 \u00b1 0.06 \u00b5U\/mg; p = 0.06) samples. Decreased ubiquitin expression in both cardiomyopathy groups (ICM vs. control: p &lt; 0.001; DCM vs. control: p &lt; 0.001), as well as less ubiquitin-positive deposits in ICM-damaged tissue (ICM: 4.19% \u00b1 0.60%, control: 6.28% \u00b1 0.40%, p = 0.022), were detected. E3-ligase MuRF1 protein expression (p = 0.62), NADPH-oxidase activity (p = 0.63), and AIF-positive cells (p = 0.50). Statistical trends were detected for reduced MAFbx protein expression in the DCM-group (p = 0.07). Different levels of UPS components, E3 ligases, and UPS activation markers were observed in myocardial tissue from patients affected by DCM and ICM, suggesting differential involvement of the UPS in the underlying pathologies.<\/jats:p>","DOI":"10.3390\/ijms20246354","type":"journal-article","created":{"date-parts":[[2019,12,20]],"date-time":"2019-12-20T03:19:36Z","timestamp":1576811976000},"page":"6354","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["The Ubiquitin Proteasome System in Ischemic and Dilated Cardiomyopathy"],"prefix":"10.3390","volume":"20","author":[{"given":"Sabine","family":"Sp\u00e4nig","sequence":"first","affiliation":[{"name":"Department of Cardiac Surgery, Heart Center Leipzig, University Leipzig, 04289 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Kellermann","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Heart Center Leipzig, University Leipzig, 04289 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja-Theresa","family":"Dieterlen","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Heart Center Leipzig, University Leipzig, 04289 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thilo","family":"Noack","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Heart Center Leipzig, University Leipzig, 04289 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Lehmann","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Heart Center Leipzig, University Leipzig, 04289 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Borger","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Heart Center Leipzig, University Leipzig, 04289 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9239-2341","authenticated-orcid":false,"given":"Jens","family":"Garbade","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Heart Center Leipzig, University Leipzig, 04289 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4688-2358","authenticated-orcid":false,"given":"Yaron D.","family":"Barac","sequence":"additional","affiliation":[{"name":"The Cardiothoracic Surgery Department, Rabin Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"Emrich","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Heart Center Leipzig, University Leipzig, 04289 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2322","DOI":"10.1089\/ars.2013.5823","article-title":"Targeting the Ubiquitin-Proteasome System in Heart Disease: The Basis for New Therapeutic Strategies","volume":"21","author":"Drews","year":"2014","journal-title":"Antioxid. 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