{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T15:24:31Z","timestamp":1777994671680,"version":"3.51.4"},"reference-count":56,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T00:00:00Z","timestamp":1695254400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>The beta-adrenergic system is a potent stimulus for enhancing cardiac output that may become deleterious when energy metabolism is compromised as in heart failure. We thus examined whether the AMP-activated protein kinase (AMPK) that is activated in response to energy depletion may control the beta-adrenergic pathway. We studied the cardiac response to beta-adrenergic stimulation of AMPK\u03b12-\/- mice or to pharmacological AMPK activation on contractile function, calcium current, cAMP content and expression of adenylyl cyclase 5 (AC5), a rate limiting step of the beta-adrenergic pathway. In AMPK\u03b12-\/- mice the expression of AC5 (+50%), the dose response curve of left ventricular developed pressure to isoprenaline (p&lt;0.001) or the response to forskolin, an activator of AC (+25%), were significantly increased compared to WT heart. Similarly, the response of L-type calcium current to 3-isobutyl-l-methylxanthine (IBMX), a phosphodiesterase inhibitor was significantly higher in KO (+98%, p&lt;0.01) than WT (+57%) isolated cardiomyocytes. Conversely, pharmacological activation of AMPK by 5-aminoimidazole-4-carboxamide riboside (AICAR) induced a 45% decrease in AC5 expression (p&lt;0.001) and a 40% decrease of cAMP content (P&lt;0.001) as measured by fluorescence resonance energy transfer (FRET) compared to unstimulated rat cardiomyocytes. Finally, in experimental pressure overload-induced cardiac dysfunction, AMPK activation was associated with a decreased expression of AC5 that was blunted in AMPK\u03b12-\/- mice. The results show that AMPK activation down-regulates AC5 expression and blunts the beta-adrenergic cascade. This crosstalk between AMPK and beta-adrenergic pathways may participate in a compensatory energy sparing mechanism in dysfunctional myocardium.<\/jats:p>","DOI":"10.1371\/journal.pone.0292015","type":"journal-article","created":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T17:39:23Z","timestamp":1695317963000},"page":"e0292015","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Modulation of cardiac cAMP signaling by AMPK and its adjustments in pressure overload-induced myocardial dysfunction in rat and 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Ishikawa","year":"1994","journal-title":"The Journal of clinical investigation"},{"issue":"4","key":"pone.0292015.ref019","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/nrd2827","article-title":"Capturing adenylyl cyclases as potential drug targets.","volume":"8","author":"S Pierre","year":"2009","journal-title":"Nat Rev Drug Discov"},{"issue":"1","key":"pone.0292015.ref020","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbrc.2016.04.123","article-title":"Disruption of Epac1 protects the heart from adenylyl cyclase type 5-mediated cardiac dysfunction","volume":"475","author":"W Cai","year":"2016","journal-title":"Biochem Biophys Res Commun"},{"issue":"3","key":"pone.0292015.ref021","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1161\/01.RES.80.3.297","article-title":"The adenylyl cyclases as integrators of transmembrane signal transduction","volume":"80","author":"Y Ishikawa","year":"1997","journal-title":"Circulation 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Neubauer","year":"2007","journal-title":"N Engl J Med"},{"issue":"4","key":"pone.0292015.ref024","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/S0022-2828(03)00015-4","article-title":"Alterations in the myocardial creatine kinase system precede the development of contractile dysfunction in beta(1)-adrenergic receptor transgenic mice.","volume":"35","author":"M Spindler","year":"2003","journal-title":"Journal of molecular and cellular cardiology"},{"issue":"1","key":"pone.0292015.ref025","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1161\/01.RES.85.1.68","article-title":"Subcellular creatine kinase alterations. Implications in heart failure","volume":"85","author":"E De Sousa","year":"1999","journal-title":"Circulation research"},{"issue":"Pt 2","key":"pone.0292015.ref026","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1113\/jphysiol.2003.045104","article-title":"Depressed mitochondrial transcription factors and oxidative capacity in rat failing cardiac and skeletal muscles","volume":"551","author":"A Garnier","year":"2003","journal-title":"The Journal of physiology"},{"issue":"Pt 1","key":"pone.0292015.ref027","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1042\/bst0310216","article-title":"Physiological role of AMP-activated protein kinase (AMPK): insights from knockout mouse models.","volume":"31","author":"B Viollet","year":"2003","journal-title":"Biochem Soc Trans"},{"issue":"Pt 21","key":"pone.0292015.ref028","doi-asserted-by":"crossref","first-page":"5181","DOI":"10.1113\/jphysiol.2008.157677","article-title":"Local energetic regulation of sarcoplasmic and myosin ATPase is differently impaired in rats with heart failure","volume":"586","author":"F Joubert","year":"2008","journal-title":"The Journal of physiology"},{"issue":"1","key":"pone.0292015.ref029","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1096\/fj.04-2173com","article-title":"Coordinated changes in mitochondrial function and biogenesis in healthy and diseased human skeletal muscle","volume":"19","author":"A Garnier","year":"2005","journal-title":"FASEB journal: official publication of the Federation of American Societies for Experimental Biology"},{"issue":"11","key":"pone.0292015.ref030","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1096\/fj.02-0784com","article-title":"Cyclic AMP compartmentation due to increased cAMP-phosphodiesterase activity in transgenic mice with a cardiac-directed expression of the human adenylyl cyclase type 8 (AC8).","volume":"17","author":"M Georget","year":"2003","journal-title":"FASEB journal: official publication of the 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adenylate cyclases type 5 and 6: A progress report","volume":"535","author":"MA Beazely","year":"2006","journal-title":"Eur J Pharmacol"},{"issue":"17","key":"pone.0292015.ref034","doi-asserted-by":"crossref","first-page":"9986","DOI":"10.1073\/pnas.1733772100","article-title":"Disruption of type 5 adenylyl cyclase gene preserves cardiac function against pressure overload","volume":"100","author":"S Okumura","year":"2003","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"16","key":"pone.0292015.ref035","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.1161\/CIRCULATIONAHA.112.001212","article-title":"Type 5 adenylyl cyclase increases oxidative stress by transcriptional regulation of manganese superoxide dismutase via the SIRT1\/FoxO3a pathway","volume":"127","author":"L Lai","year":"2013","journal-title":"Circulation"},{"issue":"3","key":"pone.0292015.ref036","doi-asserted-by":"crossref","first-page":"H240","DOI":"10.1152\/ajpheart.00630.2014","article-title":"Overexpression of adenylyl cyclase type 5 (AC5) confers a proarrhythmic substrate to the heart.","volume":"308","author":"Z Zhao","year":"2015","journal-title":"American journal of physiology Heart and circulatory physiology"},{"issue":"1","key":"pone.0292015.ref037","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1161\/CIRCULATIONAHA.107.730069","article-title":"Adenylyl cyclase type 6 deletion decreases left ventricular function via impaired calcium handling","volume":"117","author":"T Tang","year":"2008","journal-title":"Circulation"},{"issue":"5","key":"pone.0292015.ref038","doi-asserted-by":"crossref","first-page":"H1776","DOI":"10.1152\/ajpheart.00050.2009","article-title":"Adenylyl cyclase type 5 protein expression during cardiac development and stress","volume":"297","author":"CL Hu","year":"2009","journal-title":"American journal of physiology Heart and circulatory physiology"},{"key":"pone.0292015.ref039","doi-asserted-by":"crossref","first-page":"10856","DOI":"10.1038\/ncomms10856","article-title":"AMPK antagonizes hepatic glucagon-stimulated cyclic AMP signalling via phosphorylation-induced activation of cyclic nucleotide phosphodiesterase 4B.","volume":"7","author":"M Johanns","year":"2016","journal-title":"Nat Commun."},{"issue":"1","key":"pone.0292015.ref040","doi-asserted-by":"crossref","first-page":"H1","DOI":"10.1152\/ajpheart.00080.2013","article-title":"Adenylyl cyclase type 5 in cardiac disease, metabolism, and aging.","volume":"305","author":"SF Vatner","year":"2013","journal-title":"American journal of physiology Heart and circulatory physiology."},{"key":"pone.0292015.ref041","doi-asserted-by":"crossref","first-page":"425","DOI":"10.3389\/fphys.2020.00425","article-title":"Metformin Ameliorates Diabetic Cardiomyopathy by Activating the PK2\/PKR Pathway.","volume":"11","author":"Z Yang","year":"2020","journal-title":"Frontiers in physiology."},{"issue":"9","key":"pone.0292015.ref042","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1161\/CIRCRESAHA.107.167817","article-title":"Spatiotemporal dynamics of beta-adrenergic cAMP signals and L-type Ca2+ channel regulation in adult rat ventricular myocytes: role of phosphodiesterases","volume":"102","author":"J Leroy","year":"2008","journal-title":"Circulation research"},{"issue":"48","key":"pone.0292015.ref043","doi-asserted-by":"crossref","first-page":"36662","DOI":"10.1074\/jbc.M606676200","article-title":"Regulation of AMP-activated protein kinase by multisite phosphorylation in response to agents that elevate cellular cAMP","volume":"281","author":"RL Hurley","year":"2006","journal-title":"The Journal of biological chemistry"},{"issue":"Pt 1","key":"pone.0292015.ref044","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1113\/jphysiol.2003.055095","article-title":"Energy metabolism in heart failure","volume":"555","author":"R Ventura-Clapier","year":"2004","journal-title":"The Journal of physiology"},{"issue":"5","key":"pone.0292015.ref045","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1161\/01.HYP.0000144292.69599.0c","article-title":"Mechanisms for increased glycolysis in the hypertrophied rat heart","volume":"44","author":"L Nascimben","year":"2004","journal-title":"Hypertension"},{"issue":"4","key":"pone.0292015.ref046","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.cardiores.2005.04.018","article-title":"Exacerbation of heart failure in adiponectin-deficient mice due to impaired regulation of AMPK and glucose metabolism","volume":"67","author":"Y Liao","year":"2005","journal-title":"Cardiovasc Res"},{"key":"pone.0292015.ref047","article-title":"AMPK blunts chronic heart failure by inhibiting autophagy","volume":"38","author":"4","year":"2018","journal-title":"Biosci Rep"},{"key":"pone.0292015.ref048","doi-asserted-by":"crossref","first-page":"707399","DOI":"10.3389\/fphar.2021.707399","article-title":"Trimetazidine Attenuates Heart Failure by Improving Myocardial Metabolism via AMPK.","volume":"12","author":"H Shu","year":"2021","journal-title":"Front Pharmacol"},{"key":"pone.0292015.ref049","doi-asserted-by":"crossref","first-page":"109106","DOI":"10.1016\/j.biopha.2019.109106","article-title":"The cardioprotective effects of carvedilol on ischemia and reperfusion injury by AMPK signaling pathway","volume":"117","author":"H Hu","year":"2019","journal-title":"Biomed Pharmacother"},{"issue":"1","key":"pone.0292015.ref050","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1172\/JCI114985","article-title":"Decreased Gs alpha mRNA levels accompany the fall in Gs and adenylyl cyclase activities in compensated left ventricular hypertrophy. 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