{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:09:10Z","timestamp":1760141350132,"version":"build-2065373602"},"reference-count":39,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,6,7]],"date-time":"2016-06-07T00:00:00Z","timestamp":1465257600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cell Biochemistry &amp;amp; Function"],"published-print":{"date-parts":[[2016,7]]},"abstract":"<jats:p>Increase in 4\u2010hydroxy\u20102\u2010nonenal (4HNE) due to oxidative stress has been observed in a variety of cardiac diseases such as diabetic cardiomyopathy. 4HNE exerts a damaging effect in the myocardium by interfering with subcellular organelles like mitochondria by forming adducts. Therefore, we hypothesized that increased 4HNE adduct formation in the heart results in proteasome inactivation in isoproterenol (ISO)\u2010infused type 1 diabetes mellitus (DM) rats. Eight\u2010week\u2010old male Sprague Dawley rats were injected with streptozotocin (STZ, 65\u2009mg\u2009kg<jats:sup>\u22121<\/jats:sup>). The rats were infused with ISO (5\u2009mg\u2009kg<jats:sup>\u22121<\/jats:sup>) for 2\u2009weeks by mini pumps, after 8\u2009weeks of STZ injection. We studied normal control (<jats:italic>n<\/jats:italic>\u2009=\u20098) and DM\u2009+\u2009ISO (<jats:italic>n<\/jats:italic>\u2009=\u200910) groups. Cardiac performance was assessed by echocardiography and Millar catheter at the end of the protocol at 20\u2009weeks. Initially, we found an increase in 4HNE adducts in the hearts of the DM\u2009+\u2009ISO group. There was also a decrease in myocardial proteasomal peptidase (chymotrypsin and trypsin\u2010like) activity. Increases in cardiomyocyte area (446\u2009\u00b1\u200932\u00b77 vs 221\u2009\u00b1\u200910\u00b783) (\u00b5m<jats:sup>2<\/jats:sup>), per cent area of cardiac fibrosis (7\u00b74\u2009\u00b1\u20090\u00b77 vs 2\u00b77\u2009\u00b1\u20090\u00b75) and cardiac dysfunction were also found in DM\u2009+\u2009ISO (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090\u00b705) relative to controls. We also found increased 4HNE adduct formation on proteasomal subunits. Furthermore, reduced aldehyde dehydrogenase 2 activity was observed in the myocardium of the DM\u2009+\u2009ISO group. Treatment with 4HNE (100\u2009\u03bcM) for 4\u2009h on cultured H9c2 cardiomyocytes attenuated proteasome activity. Therefore, we conclude that the 4HNE\u2010induced decrease in proteasome activity may be involved in the cardiac pathology in STZ\u2010injected rats infused with ISO. Copyright \u00a9 2016 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/cbf.3195","type":"journal-article","created":{"date-parts":[[2016,6,7]],"date-time":"2016-06-07T19:39:15Z","timestamp":1465328355000},"page":"334-342","source":"Crossref","is-referenced-by-count":7,"title":["Increased 4\u2010hydroxy\u20102\u2010nonenal\u2010induced proteasome dysfunction is correlated with cardiac damage in streptozotocin\u2010injected rats with isoproterenol infusion"],"prefix":"10.1002","volume":"34","author":[{"given":"Mandar","family":"Deshpande","sequence":"first","affiliation":[{"name":"Division of Hypertension and Vascular Research, Department of Internal Medicine Henry Ford Health System  Detroit MI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vishal R.","family":"Mali","sequence":"additional","affiliation":[{"name":"Division of Hypertension and Vascular Research, Department of Internal Medicine Henry Ford Health System  Detroit MI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guodong","family":"Pan","sequence":"additional","affiliation":[{"name":"Division of Hypertension and Vascular Research, Department of Internal Medicine Henry Ford Health System  Detroit MI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiang","family":"Xu","sequence":"additional","affiliation":[{"name":"Division of Hypertension and Vascular Research, Department of Internal Medicine Henry Ford Health System  Detroit MI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao\u2010Ping","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Hypertension and Vascular Research, Department of Internal Medicine Henry Ford Health System  Detroit MI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajarajan A.","family":"Thandavarayan","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, Center for Cardiovascular Regeneration Houston Methodist Research Institute  Houston TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suresh Selvaraj","family":"Palaniyandi","sequence":"additional","affiliation":[{"name":"Division of Hypertension and Vascular Research, Department of Internal Medicine Henry Ford Health System  Detroit MI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,6,7]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0163-7827(03)00014-6"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.2011.05641.x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.20553"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0891-5849(91)90192-6"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M100142200"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2004.11.003"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2006.02.003"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-009-9074-5"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1179\/135100007X200308"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(97)00065-1"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2008.10.055"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0052764"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2007.12.009"},{"issue":"2","key":"e_1_2_7_15_1","first-page":"289","article-title":"Proteasome activity in experimental diabetes","volume":"1","author":"Alexandrova A","year":"2006","journal-title":"Central Eur J Bio"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.2337\/db08-1565"},{"key":"e_1_2_7_17_1","doi-asserted-by":"crossref","DOI":"10.1096\/fasebj.24.1_supplement.572.3","article-title":"Aldehyde dehydrogenase activator attenuates diabetic cardiomyopathy; 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