{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T07:32:43Z","timestamp":1772782363578,"version":"3.50.1"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2010,10,29]]},"abstract":"<jats:sec>\n            <jats:title>\n              <jats:underline>Rationale:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>Proteasomal degradation is altered in many disease phenotypes including cardiac hypertrophy, a prevalent condition leading to heart failure. Our recent investigations identified heterogeneous subpopulations of proteasome complexes in the heart and implicated multiple mechanisms for their regulation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Objective:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>The study aimed at identification of molecular mechanisms changing proteasome function in the hypertrophic heart.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Method and Results:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>Proteasome function, expression, and assembly were analyzed during the development of cardiac hypertrophy induced by \u03b2-adrenergic stimulation. The analysis revealed, for the first time, divergent regulation of proteasome function in cardiac hypertrophy. Proteasome complexes have 3 different proteolytic activities, which are ATP-dependent for 26S complexes (19S assembled with 20S) and ATP-independent for 20S core particles. The 26S activities were enhanced in hypertrophic hearts, partially because of increased expression and assembly of 19S subunits with 20S core complexes. In contrast, caspase- and trypsin-like 20S activities were significantly decreased. Activation of endogenous cAMP-dependent protein kinase (PKA) rescued the depressed 20S functions, supporting the notion that PKA signaling is a positive regulator of protein degradation in the heart. Chymotrypsin-like 20S activity was stably maintained during cardiac remodeling, indicating a switch in proteasome subpopulations, which was supported by altered expression and incorporation of inducible \u03b2 subunits.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Conclusions:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>Three novel mechanisms for the regulation of proteasome activities were discovered in the development of cardiac hypertrophy: (1) increased incorporation of inducible subunits in 20S proteasomes; (2) enhanced 20S sensitivity to PKA activation; and (3) increased 26S assembly. PKA modulation of proteasome complexes may provide a novel therapeutic avenue for restoration of cardiac function in the diseased myocardium.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.110.222364","type":"journal-article","created":{"date-parts":[[2010,9,3]],"date-time":"2010-09-03T02:43:10Z","timestamp":1283481790000},"page":"1094-1101","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":99,"title":["Differential Regulation of Proteasome Function in Isoproterenol-Induced Cardiac Hypertrophy"],"prefix":"10.1161","volume":"107","author":[{"given":"Oliver","family":"Drews","sequence":"first","affiliation":[{"name":"From the Departments of Physiology and Medicine (O.D., D.L., P.P.), Anesthesiology (J.S., Y.W.), David Geffen School of Medicine, University of California, Los Angeles, CA, USA; and Department of Cardiovascular Medicine (O.T.), National Cardiovascular Center, Osaka, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Osamu","family":"Tsukamoto","sequence":"additional","affiliation":[{"name":"From the Departments of Physiology and Medicine (O.D., D.L., P.P.), Anesthesiology (J.S., Y.W.), David Geffen School of Medicine, University of California, Los Angeles, CA, USA; and Department of Cardiovascular Medicine (O.T.), National Cardiovascular Center, Osaka, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Liem","sequence":"additional","affiliation":[{"name":"From the Departments of Physiology and Medicine (O.D., D.L., P.P.), Anesthesiology (J.S., Y.W.), David Geffen School of Medicine, University of California, Los Angeles, CA, USA; and Department of Cardiovascular Medicine (O.T.), National Cardiovascular Center, Osaka, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Streicher","sequence":"additional","affiliation":[{"name":"From the Departments of Physiology and Medicine (O.D., D.L., P.P.), Anesthesiology (J.S., Y.W.), David Geffen School of Medicine, University of California, Los Angeles, CA, USA; and Department of Cardiovascular Medicine (O.T.), National Cardiovascular Center, Osaka, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yibin","family":"Wang","sequence":"additional","affiliation":[{"name":"From the Departments of Physiology and Medicine (O.D., D.L., P.P.), Anesthesiology (J.S., Y.W.), David Geffen School of Medicine, University of California, Los Angeles, CA, USA; and Department of Cardiovascular Medicine (O.T.), National Cardiovascular Center, Osaka, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peipei","family":"Ping","sequence":"additional","affiliation":[{"name":"From the Departments of Physiology and Medicine (O.D., D.L., P.P.), Anesthesiology (J.S., Y.W.), David Geffen School of Medicine, University of California, Los Angeles, CA, USA; and Department of Cardiovascular Medicine (O.T.), National Cardiovascular Center, Osaka, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M700187-MCP200"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1357-2725(02)00381-3"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2007.07.038"},{"key":"e_1_3_4_5_2","article-title":"Multiple cardiac proteasome subtypes differ in their susceptibility to proteasome inhibitors","author":"Kloss A","year":"2009","unstructured":"Kloss A, Meiners S, Ludwig A, Dahlmann B Multiple cardiac proteasome subtypes differ in their susceptibility to proteasome inhibitors. Cardiovasc Res. 2009.","journal-title":"Cardiovasc Res."},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M800064-MCP200"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000252342.61447.a2"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2005.7.538"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.101.14.1634"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000102042.83024.ca"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199910213411706"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/415206a"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.1997.0508"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10741-007-9007-4"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2006.08.002"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0510113103"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1063866"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2004.03.012"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.106.649863"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00196.2007"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.106.637827"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.05.008"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000237386.98506.f7"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08065"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.11.7.9212076"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M206279200"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.65.070196.004101"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.67.1.425"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.68.1.1015"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.32.22123"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/365264a0"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/365262a0"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00532.2008"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000247932.71270.2c"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.200600574"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000237389.40000.02"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2828(85)80130-9"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1090"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-2872"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.23224"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2007.06659.x"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-2218"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1002\/psc.1107"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-07-171637"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-5521(01)00056-4"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr0502504"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M702439200"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2008.11.001"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.904557"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2009.07.022"}],"container-title":["Circulation Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCRESAHA.110.222364","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T03:34:01Z","timestamp":1715571241000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCRESAHA.110.222364"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,10,29]]},"references-count":49,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2010,10,29]]}},"alternative-id":["10.1161\/CIRCRESAHA.110.222364"],"URL":"https:\/\/doi.org\/10.1161\/circresaha.110.222364","relation":{},"ISSN":["0009-7330","1524-4571"],"issn-type":[{"value":"0009-7330","type":"print"},{"value":"1524-4571","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,10,29]]},"assertion":[{"value":"2010-04-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2010-08-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2010-09-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}