{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T20:50:39Z","timestamp":1764276639708,"version":"3.37.3"},"reference-count":63,"publisher":"Wiley","license":[{"start":{"date-parts":[[2012,7,26]],"date-time":"2012-07-26T00:00:00Z","timestamp":1343260800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["2PO1 HL62426","1F32 HL096143"],"award-info":[{"award-number":["2PO1 HL62426","1F32 HL096143"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["2PO1 HL62426","1F32 HL096143"],"award-info":[{"award-number":["2PO1 HL62426","1F32 HL096143"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Marian Falk Medical Research Trust","award":["2PO1 HL62426","1F32 HL096143"],"award-info":[{"award-number":["2PO1 HL62426","1F32 HL096143"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Signal Transduction"],"published-print":{"date-parts":[[2012,7,26]]},"abstract":"<jats:p>Intracellular nitric oxide (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\"><mml:mrow><mml:msub><mml:mrow><mml:mtext>NO<\/mml:mtext><\/mml:mrow><mml:mtext>i<\/mml:mtext><\/mml:msub><\/mml:mrow><\/mml:math>) is a physiological regulator of excitation-contraction coupling, but is also involved in the development of cardiac dysfunction during hypertrophy and heart failure. To determine whether contractile activity regulates nitric oxide synthase (NOS) expression, spontaneously contracting, neonatal rat ventricular myocytes (NRVM) were treat with L-type calcium channel blockers (nifedipine and verapamil) or myosin II ATPase inhibitors (butanedione monoxime (BDM) and blebbistatin) to produce contractile arrest. Both types of inhibitors significantly reduced iNOS but not eNOS expression, and also reduced<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\"><mml:mrow><mml:msub><mml:mrow><mml:mtext>NO<\/mml:mtext><\/mml:mrow><mml:mtext>i<\/mml:mtext><\/mml:msub><\/mml:mrow><\/mml:math>production. Inhibiting contractile activity also reduced focal adhesion kinase (FAK) and AKT phosphorylation. Contraction-induced iNOS expression required FAK and phosphatidylinositol 3-kinase (PI(3)K), as both PF573228 and LY294002 (10\u2009<jats:italic>\u03bc<\/jats:italic>M, 24\u2009h) eliminated contraction-induced iNOS expression. Similarly, shRNAs specific for FAK (shFAK) caused FAK knockdown, reduced AKT phosphorylation at T308 and S473, and reduced iNOS expression. In contrast, shRNA-mediated knockdown of PYK2, the other member of the FAK-family of protein tyrosine kinases, had much less of an effect. Conversely, overexpression of a constitutively active form of FAK (CD2-FAK) or AKT (Myr-AKT) reversed the inhibitory effect of BDM on iNOS expression and<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M3\"><mml:mrow><mml:msub><mml:mrow><mml:mtext>NO<\/mml:mtext><\/mml:mrow><mml:mtext>i<\/mml:mtext><\/mml:msub><\/mml:mrow><\/mml:math>production. Thus, contraction-induced iNOS expression and<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M4\"><mml:mrow><mml:msub><mml:mrow><mml:mtext>NO<\/mml:mtext><\/mml:mrow><mml:mtext>i<\/mml:mtext><\/mml:msub><\/mml:mrow><\/mml:math>production in NRVM are mediated via a FAK-PI(3)K-AKT signaling pathway.<\/jats:p>","DOI":"10.1155\/2012\/473410","type":"journal-article","created":{"date-parts":[[2012,7,27]],"date-time":"2012-07-27T03:11:54Z","timestamp":1343358714000},"page":"1-11","source":"Crossref","is-referenced-by-count":7,"title":["Contractile Activity Regulates Inducible Nitric Oxide Synthase Expression and NO<sub>i<\/sub>Production in Cardiomyocytes via a FAK-Dependent Signaling Pathway"],"prefix":"10.1155","volume":"2012","author":[{"given":"Miensheng","family":"Chu","sequence":"first","affiliation":[{"name":"Cardiovascular Institute, Loyola University Chicago Stritch School of Medicine, 2160 South First Avenue, Maywood, IL 60153, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yevgeniya","family":"Koshman","sequence":"additional","affiliation":[{"name":"Cardiovascular Institute, Loyola University Chicago Stritch School of Medicine, 2160 South First Avenue, Maywood, IL 60153, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rekha","family":"Iyengar","sequence":"additional","affiliation":[{"name":"Cardiovascular Institute, Loyola University Chicago Stritch School of Medicine, 2160 South First Avenue, Maywood, IL 60153, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taehoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Cardiovascular Institute, Loyola University Chicago Stritch School of Medicine, 2160 South First Avenue, Maywood, IL 60153, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brenda","family":"Russell","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL 60612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allen M.","family":"Samarel","sequence":"additional","affiliation":[{"name":"Cardiovascular Institute, Loyola University Chicago Stritch School of Medicine, 2160 South First Avenue, Maywood, IL 60153, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","reference":[{"issue":"44","key":"1","doi-asserted-by":"crossref","first-page":"27580","DOI":"10.1016\/S0021-9258(18)47024-X","volume":"269","year":"1994","journal-title":"Journal of Biological Chemistry"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.2.657"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.37.22810"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1038\/416005a"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000088351.58510.21"},{"issue":"5","key":"6","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1161\/01.CIR.95.5.1111","volume":"95","year":"1997","journal-title":"Circulation"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1161\/hc0202.102015"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000124231.98250.A8"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(99)00237-0"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1096\/fj.06-5717fje"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-003-0488-x"},{"key":"12","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00749.2005"},{"issue":"12","key":"13","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1161\/hh2401.101084","volume":"89","year":"2001","journal-title":"Circulation Research"},{"key":"14","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.126805"},{"issue":"4","key":"15","first-page":"H1067","volume":"261","year":"1991","journal-title":"American Journal of Physiology"},{"key":"16","doi-asserted-by":"crossref","first-page":"2432","DOI":"10.1161\/ATVBAHA.111.235549","volume":"31","year":"2011","journal-title":"Arteriosclerosis, Thrombosis, and Vascular Biology"},{"key":"17","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000023201.41774.EA"},{"key":"18","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(02)00192-4"},{"key":"19","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M008869200"},{"issue":"5","key":"20","first-page":"H1695","volume":"278","year":"2000","journal-title":"American Journal of Physiology"},{"issue":"32","key":"21","doi-asserted-by":"crossref","first-page":"20567","DOI":"10.1016\/S0021-9258(17)32031-8","volume":"269","year":"1994","journal-title":"Journal of Biological Chemistry"},{"issue":"6","key":"22","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1161\/01.CIR.101.6.660","volume":"101","year":"2000","journal-title":"Circulation"},{"issue":"10","key":"23","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1161\/hh2201.099434","volume":"89","year":"2001","journal-title":"Circulation Research"},{"issue":"10","key":"24","doi-asserted-by":"crossref","first-page":"5623","DOI":"10.1128\/MCB.16.10.5623","volume":"16","year":"1996","journal-title":"Molecular and Cellular Biology"},{"issue":"13","key":"25","doi-asserted-by":"crossref","first-page":"2446","DOI":"10.1021\/ac9801723","volume":"70","year":"1998","journal-title":"Analytical Chemistry"},{"key":"26","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(98)00440-2"},{"key":"27","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2002.023341"},{"issue":"5","key":"28","doi-asserted-by":"crossref","first-page":"C1447","DOI":"10.1152\/ajpcell.1996.271.5.C01447","volume":"271","year":"1996","journal-title":"American Journal of Physiology"},{"issue":"2","key":"29","doi-asserted-by":"crossref","first-page":"C394","DOI":"10.1152\/ajpcell.1997.273.2.C394","volume":"273","year":"1997","journal-title":"American Journal of Physiologys"},{"issue":"5","key":"30","doi-asserted-by":"crossref","first-page":"C1226","DOI":"10.1152\/ajpcell.1998.274.5.C1226","volume":"274","year":"1998","journal-title":"American Journal of Physiology"},{"key":"31","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1001-867"},{"key":"32","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M606695200"},{"issue":"7","key":"33","doi-asserted-by":"crossref","first-page":"5241","DOI":"10.1016\/S0021-9258(17)37680-9","volume":"269","year":"1994","journal-title":"Journal of Biological Chemistry"},{"key":"34","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00401.2008"},{"key":"35","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M804036200"},{"issue":"49","key":"36","doi-asserted-by":"crossref","first-page":"31229","DOI":"10.1016\/S0021-9258(18)47413-3","volume":"269","year":"1994","journal-title":"Journal of Biological Chemistry"},{"key":"37","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.21.10148"},{"key":"38","doi-asserted-by":"publisher","DOI":"10.1016\/0167-4889(95)00176-X"},{"key":"39","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.42.26329"},{"key":"40","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.18.12361"},{"key":"41","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M313265200"},{"key":"42","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2008.04.002"},{"key":"43","doi-asserted-by":"publisher","DOI":"10.1038\/21224"},{"key":"44","doi-asserted-by":"publisher","DOI":"10.1038\/21218"},{"key":"45","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200304-562OC"},{"issue":"3","key":"46","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1161\/01.RES.81.3.372","volume":"81","year":"1997","journal-title":"Circulation Research"},{"issue":"4","key":"47","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1161\/01.CIR.96.4.1320","volume":"96","year":"1997","journal-title":"Circulation"},{"issue":"11","key":"48","first-page":"E68","volume":"88","year":"2001","journal-title":"Circulation Research"},{"key":"49","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.2008.05100.x"},{"issue":"1","key":"50","first-page":"H331","volume":"277","year":"1999","journal-title":"American Journal of Physiology"},{"key":"51","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.toxlet.2011.09.015","volume":"207","year":"2011","journal-title":"Toxicology Letters"},{"issue":"7","key":"52","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1161\/01.RES.87.7.558","volume":"87","year":"2000","journal-title":"Circulation Research"},{"key":"53","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2008.163824"},{"key":"54","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.22.8019-8029.2003"},{"key":"55","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000252830.01581.fd"},{"issue":"6","key":"56","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1161\/hc3201.092284","volume":"104","year":"2001","journal-title":"Circulation"},{"issue":"4","key":"57","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1161\/hh1601.094993","volume":"89","year":"2001","journal-title":"Circulation Research"},{"key":"58","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00546.2005"},{"key":"59","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000264081.78659.45"},{"key":"60","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200213265"},{"key":"61","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00245.2004"},{"key":"62","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.2001.1462"},{"key":"63","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2005.09.011"}],"container-title":["Journal of Signal Transduction"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/archive\/2012\/473410.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/archive\/2012\/473410.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/archive\/2012\/473410.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,23]],"date-time":"2022-01-23T04:48:17Z","timestamp":1642913297000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.hindawi.com\/journals\/jst\/2012\/473410\/"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,7,26]]},"references-count":63,"alternative-id":["473410","473410"],"URL":"https:\/\/doi.org\/10.1155\/2012\/473410","relation":{},"ISSN":["2090-1739","2090-1747"],"issn-type":[{"type":"print","value":"2090-1739"},{"type":"electronic","value":"2090-1747"}],"subject":[],"published":{"date-parts":[[2012,7,26]]}}}