{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T15:21:17Z","timestamp":1764688877429},"reference-count":16,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2000,9,12]]},"abstract":"<jats:p>\n            <jats:italic>Background<\/jats:italic>\n            \u2014The mechanism(s) responsible for the persistent coexpression of tumor necrosis factor-\u03b1 (TNF-\u03b1) and nitric oxide (NO) in the failing heart is unknown.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Methods and Results<\/jats:italic>\n            \u2014To determine whether NO was sufficient to provoke TNF-\u03b1 biosynthesis, we examined the effects of an NO donor, S-nitroso-N-acetyl penicillamine (SNAP), in buffer-perfused Langendorff hearts. SNAP (1 \u03bcmol\/L) treatment resulted in a time- and dose-dependent increase in myocardial TNF-\u03b1 mRNA and protein biosynthesis in adult cat hearts. The effects of SNAP were completely abrogated by a NO quenching agent, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (C-PTIO), and mimicked by sodium nitroprusside. Electrophoretic mobility shift assays demonstrated that SNAP treatment led to the rapid induction of nuclear factor kappa-beta (NF-\u03baB) but not AP-1. The importance of the cGMP pathway in terms of mediating NO-induced TNF-\u03b1 biosynthesis was shown by studies that demonstrated that 8-bromo-cGMP mimicked the effects of SNAP and that the effects of SNAP could be completely abrogated using a cGMP antagonist, 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one (ODQ), or protein kinase G antagonist (Rp-8-Br-cGMPS). SNAP and 8-Br-cGMP were both sufficient to lead to the site-specific phosphorylation (serine 32) and degradation of I\u03baB\u03b1 in isolated cardiac myocytes. Finally, protein kinase G was sufficient to directly phosphorylate I\u03baB\u03b1 on serine 32, a critical step in the activation of NF-\u03baB.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Conclusions<\/jats:italic>\n            \u2014These studies show that NO provokes TNF-\u03b1 biosynthesis through a cGMP-dependent pathway, which suggests that the coincident expression of TNF-\u03b1 and NO may foster self-sustaining positive autocrine\/paracrine feedback inflammatory circuits within the failing heart.\n          <\/jats:p>","DOI":"10.1161\/01.cir.102.11.1302","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:42:29Z","timestamp":1339461749000},"page":"1302-1307","update-policy":"http:\/\/dx.doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":64,"title":["Nitric Oxide Provokes Tumor Necrosis Factor-\u03b1 Expression in Adult Feline Myocardium Through a cGMP-Dependent Pathway"],"prefix":"10.1161","volume":"102","author":[{"given":"Dinesh","family":"Kalra","sequence":"first","affiliation":[{"name":"From the Winters Center for Heart Failure Research, Cardiology Section, Department of Medicine, Veterans Administration Medical Center and Baylor College of Medicine, Houston, Tex."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georg","family":"Baumgarten","sequence":"additional","affiliation":[{"name":"From the Winters Center for Heart Failure Research, Cardiology Section, Department of Medicine, Veterans Administration Medical Center and Baylor College of Medicine, Houston, Tex."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziad","family":"Dibbs","sequence":"additional","affiliation":[{"name":"From the Winters Center for Heart Failure Research, Cardiology Section, Department of Medicine, Veterans Administration Medical Center and Baylor College of Medicine, Houston, Tex."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukihiro","family":"Seta","sequence":"additional","affiliation":[{"name":"From the Winters Center for Heart Failure Research, Cardiology Section, Department of Medicine, Veterans Administration Medical Center and Baylor College of Medicine, Houston, Tex."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natarajan","family":"Sivasubramanian","sequence":"additional","affiliation":[{"name":"From the Winters Center for Heart Failure Research, Cardiology Section, Department of Medicine, Veterans Administration Medical Center and Baylor College of Medicine, Houston, Tex."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas L.","family":"Mann","sequence":"additional","affiliation":[{"name":"From the Winters Center for Heart Failure Research, Cardiology Section, Department of Medicine, Veterans Administration Medical Center and Baylor College of Medicine, Houston, Tex."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.81.2.187"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.93.4.704"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.93.6.1087"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116461"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.150.4.1509"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.32.2.266"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.95.5.1247"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1995.tb07287.x"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)37024-2"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1994.267.5.C1405"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1006\/cyto.1995.0056"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.161.4.1970"},{"key":"e_1_3_2_13_2","doi-asserted-by":"crossref","unstructured":"Peng HB Libby P Liao JK. Induction and stabilization of IKBa by nitric oxide mediates inhibition of NF-kB. J Biol Chem. 1995;14214\u201314219.","DOI":"10.1074\/jbc.270.23.14214"},{"key":"e_1_3_2_14_2","doi-asserted-by":"crossref","first-page":"4048","DOI":"10.4049\/jimmunol.154.8.4048","volume":"154","year":"1995","unstructured":"Eigler A, Moeller J, Endres S. Exogenous and endogenous nitric oxide attenuates tumor necrosis factor synthesis in the murine macrophage cell line RAW 264.7. J Immunol. 1995;154:4048\u20134054.","journal-title":"J Immunol"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-4141(199808)28:08<2276::AID-IMMU2276>3.0.CO;2-H"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.1996.0073"}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/01.CIR.102.11.1302","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T13:00:22Z","timestamp":1715518822000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/01.CIR.102.11.1302"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,9,12]]},"references-count":16,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2000,9,12]]}},"alternative-id":["10.1161\/01.CIR.102.11.1302"],"URL":"https:\/\/doi.org\/10.1161\/01.cir.102.11.1302","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,9,12]]},"assertion":[{"value":"2000-02-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2000-04-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2000-09-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}