Modulation of cardiac cAMP signaling by AMPK and its adjustments in pressure overload-induced myocardial dysfunction in rat and mouse.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2023
2023
Historique:
received:
12
06
2023
accepted:
11
09
2023
medline:
25
9
2023
pubmed:
21
9
2023
entrez:
21
9
2023
Statut:
epublish
Résumé
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 AMPKα2-/- 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 AMPKα2-/- mice the expression of AC5 (+50%), the dose response curve of left ventricular developed pressure to isoprenaline (p<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<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<0.001) and a 40% decrease of cAMP content (P<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 AMPKα2-/- 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.
Identifiants
pubmed: 37733758
doi: 10.1371/journal.pone.0292015
pii: PONE-D-23-18218
pmc: PMC10513315
doi:
Substances chimiques
AMP-Activated Protein Kinases
EC 2.7.11.31
Calcium
SY7Q814VUP
Adrenergic Agents
0
Calcium, Dietary
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0292015Informations de copyright
Copyright: © 2023 Garnier et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Circulation. 2007 Oct 16;116(16):1776-83
pubmed: 17893275
Circ Res. 2008 May 9;102(9):1091-100
pubmed: 18369156
Circulation. 2008 Feb 12;117(6):832-40
pubmed: 18268160
Biochem J. 1998 Aug 15;334 ( Pt 1):177-87
pubmed: 9693118
Front Pharmacol. 2021 Sep 15;12:707399
pubmed: 34603021
J Mol Cell Cardiol. 2003 Apr;35(4):389-97
pubmed: 12689818
Hypertension. 2008 Nov;52(5):918-24
pubmed: 18838626
Diabetes. 2008 Mar;57(3):696-705
pubmed: 18083782
J Physiol. 2004 Feb 15;555(Pt 1):1-13
pubmed: 14660709
Am J Physiol Heart Circ Physiol. 2007 Jun;292(6):H3136-47
pubmed: 17337600
Am J Physiol Endocrinol Metab. 2006 May;290(5):E780-8
pubmed: 16332922
Physiology (Bethesda). 2014 Mar;29(2):99-107
pubmed: 24583766
Br J Pharmacol. 1999 May;127(1):65-74
pubmed: 10369457
Cardiovasc Res. 2005 Sep 1;67(4):705-13
pubmed: 15907819
N Engl J Med. 2007 Mar 15;356(11):1140-51
pubmed: 17360992
Diabetes. 2015 Jul;64(7):2636-45
pubmed: 25732192
Physiol Rev. 2009 Jul;89(3):1025-78
pubmed: 19584320
Biochem Soc Trans. 2003 Feb;31(Pt 1):216-9
pubmed: 12546688
Circ Res. 2003 Nov 14;93(10):896-906
pubmed: 14615493
Hypertension. 2004 Nov;44(5):662-7
pubmed: 15466668
Circ Res. 1997 Mar;80(3):297-304
pubmed: 9048648
Circ Res. 1999 Jul 9;85(1):68-76
pubmed: 10400912
Exp Suppl. 2016;107:441-469
pubmed: 27812991
J Clin Invest. 1994 May;93(5):2224-9
pubmed: 8182154
Biomed Pharmacother. 2019 Sep;117:109106
pubmed: 31200253
Circulation. 2013 Apr 23;127(16):1692-701
pubmed: 23536361
Circ Res. 2009 Feb 13;104(3):403-11
pubmed: 19096023
J Physiol. 2008 Nov 1;586(21):5181-92
pubmed: 18787038
Am J Physiol Heart Circ Physiol. 2015 Feb 1;308(3):H240-9
pubmed: 25485900
Am J Physiol Heart Circ Physiol. 2007 Jul;293(1):H457-66
pubmed: 17369473
Biochem Biophys Res Commun. 2016 Jun 17;475(1):1-7
pubmed: 27117748
Circulation. 2009 May 19;119(19):2568-77
pubmed: 19414638
Nat Rev Drug Discov. 2009 Apr;8(4):321-35
pubmed: 19337273
FASEB J. 2005 Jan;19(1):43-52
pubmed: 15629894
FASEB J. 2003 Aug;17(11):1380-91
pubmed: 12890691
Am J Physiol Heart Circ Physiol. 2009 Nov;297(5):H1776-82
pubmed: 19734365
Circulation. 2001 Oct 2;104(14):1664-9
pubmed: 11581146
J Physiol. 2003 Sep 1;551(Pt 2):491-501
pubmed: 12824444
Circulation. 2008 Jan 1;117(1):61-9
pubmed: 18071070
J Biol Chem. 2006 Dec 1;281(48):36662-72
pubmed: 17023420
Heart Fail Rev. 2010 Sep;15(5):495-512
pubmed: 20658186
J Clin Invest. 1993 Mar;91(3):907-14
pubmed: 8383704
Diabetes. 2007 Mar;56(3):786-94
pubmed: 17327449
J Clin Invest. 1991 Jan;87(1):293-8
pubmed: 1824633
Nat Rev Mol Cell Biol. 2018 Feb;19(2):121-135
pubmed: 28974774
Front Physiol. 2020 May 19;11:425
pubmed: 32508669
Nat Commun. 2016 Mar 08;7:10856
pubmed: 26952277
Proc Natl Acad Sci U S A. 2003 Aug 19;100(17):9986-90
pubmed: 12904575
Am J Physiol Endocrinol Metab. 2003 Sep;285(3):E629-36
pubmed: 12759223
Front Cell Dev Biol. 2021 Oct 18;9:731015
pubmed: 34733845
J Mol Cell Cardiol. 2010 Apr;48(4):591-9
pubmed: 19913550
J Biol Chem. 2005 Aug 12;280(32):29060-6
pubmed: 15980064
Biosci Rep. 2018 Jul 18;38(4):
pubmed: 30021848
Am J Physiol Heart Circ Physiol. 2013 Jul 1;305(1):H1-8
pubmed: 23624627
Eur J Pharmacol. 2006 Mar 27;535(1-3):1-12
pubmed: 16527269
Biol Sex Differ. 2021 Sep 17;12(1):52
pubmed: 34535195