Hypercontractile cardiac phenotype in mice overexpressing the regulatory subunit PR72 of protein phosphatase 2A.
Ca2+ handling
Na+/Ca2+ exchanger
contractility
protein phosphatase 2A
protein phosphorylation
regulatory B'' subunit PPP2R3A/PR72
Journal
Frontiers in cardiovascular medicine
ISSN: 2297-055X
Titre abrégé: Front Cardiovasc Med
Pays: Switzerland
ID NLM: 101653388
Informations de publication
Date de publication:
2023
2023
Historique:
received:
13
06
2023
accepted:
22
09
2023
medline:
23
10
2023
pubmed:
23
10
2023
entrez:
23
10
2023
Statut:
epublish
Résumé
The activity, localization, and substrate specificity of the protein phosphatase 2A (PP2A) heterotrimer are controlled by various regulatory B subunits. PR72 belongs to the B'' gene family and has been shown to be upregulated in human heart failure. However, little is known about the functions of PR72 in the myocardium. To address this issue, we generated a transgenic mouse model with heart-specific overexpression of PP2A-PR72. Biochemical and physiological methods were used to determine contractility, Ca A 2.5-fold increase in PR72 expression resulted in moderate cardiac hypertrophy. Maximal ventricular pressure was increased in catheterized transgenic mice (TG) compared to wild-type (WT) littermates. This was accompanied by an increased shortening of sarcomere length and faster relaxation at the single-cell level in TG. In parallel with these findings, the peak amplitude of Ca Our results suggest that PP2A-PR72 plays an important role in regulating cardiac contractile function and Ca
Sections du résumé
Background
UNASSIGNED
The activity, localization, and substrate specificity of the protein phosphatase 2A (PP2A) heterotrimer are controlled by various regulatory B subunits. PR72 belongs to the B'' gene family and has been shown to be upregulated in human heart failure. However, little is known about the functions of PR72 in the myocardium.
Methods
UNASSIGNED
To address this issue, we generated a transgenic mouse model with heart-specific overexpression of PP2A-PR72. Biochemical and physiological methods were used to determine contractility, Ca
Results
UNASSIGNED
A 2.5-fold increase in PR72 expression resulted in moderate cardiac hypertrophy. Maximal ventricular pressure was increased in catheterized transgenic mice (TG) compared to wild-type (WT) littermates. This was accompanied by an increased shortening of sarcomere length and faster relaxation at the single-cell level in TG. In parallel with these findings, the peak amplitude of Ca
Conclusion
UNASSIGNED
Our results suggest that PP2A-PR72 plays an important role in regulating cardiac contractile function and Ca
Identifiants
pubmed: 37868783
doi: 10.3389/fcvm.2023.1239555
pmc: PMC10590119
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1239555Informations de copyright
© 2023 Herting, König, Hadova, Heinick, Müller, Pauls, Seidl, Soppa and Kirchhefer.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
Curr Opin Genet Dev. 2005 Feb;15(1):34-41
pubmed: 15661531
Mol Cell Biol. 2000 Jul;20(14):5285-99
pubmed: 10866685
J Biol Chem. 1995 Nov 3;270(44):26123-8
pubmed: 7592815
J Mol Cell Cardiol. 2016 Dec;101:127-133
pubmed: 27832939
Am J Physiol Cell Physiol. 2007 Sep;293(3):C1073-81
pubmed: 17376815
Cell Signal. 2022 Mar;91:110213
pubmed: 34902541
Circ Res. 2018 Feb 2;122(3):433-443
pubmed: 29212778
J Physiol. 2013 Mar 15;591(6):1409-32
pubmed: 23207593
Circ Res. 2010 Jul 23;107(2):294-304
pubmed: 20558820
Circ Res. 1989 Jan;64(1):104-11
pubmed: 2535795
FEBS Lett. 1990 Aug 1;268(2):355-9
pubmed: 2166691
Circ Res. 2014 Nov 7;115(11):919-28
pubmed: 25249569
J Biol Chem. 1993 Jul 15;268(20):15267-76
pubmed: 8392071
Curr Med Chem. 2009;16(25):3294-321
pubmed: 19548864
Biophys J. 2010 Aug 4;99(3):755-64
pubmed: 20682252
Circ Res. 2004 Sep 17;95(6):604-11
pubmed: 15308581
Mol Cell Proteomics. 2010 Mar;9(3):497-509
pubmed: 20037178
Eur Rev Med Pharmacol Sci. 2021 Dec;25(24):7913-7925
pubmed: 34982454
J Biol Chem. 2010 Apr 9;285(15):11078-86
pubmed: 20106966
Acta Physiol (Oxf). 2021 Jul;232(3):e13691
pubmed: 34022101
Am J Physiol Heart Circ Physiol. 2002 Oct;283(4):H1334-43
pubmed: 12234783
Am J Physiol Heart Circ Physiol. 2009 Oct;297(4):H1304-13
pubmed: 19666840
Cardiovasc Res. 2022 Mar 25;118(5):1276-1288
pubmed: 33892492
J Biol Chem. 2022 Sep;298(9):102362
pubmed: 35963431
Eur J Biochem. 2002 Jan;269(2):546-52
pubmed: 11856313
Biophys J. 1998 Jul;75(1):15-32
pubmed: 9649364
Braz J Med Biol Res. 2006 May;39(5):563-72
pubmed: 16648892
J Biol Chem. 2013 Jan 11;288(2):1032-46
pubmed: 23204520
J Biol Chem. 2003 Mar 21;278(12):10697-706
pubmed: 12524438
BMC Genomics. 2008 Aug 20;9:393
pubmed: 18715506
J Mol Cell Cardiol. 2013 Nov;64:90-8
pubmed: 24051368
Biochem Biophys Res Commun. 1989 Mar 31;159(3):871-7
pubmed: 2539153
J Physiol. 1990 Jun;425:55-70
pubmed: 2213589
Cell. 2020 Apr 30;181(3):688-701.e16
pubmed: 32315618
Front Physiol. 2020 Jan 23;10:1630
pubmed: 32038301
Proc Natl Acad Sci U S A. 2016 Nov 1;113(44):12592-12597
pubmed: 27742792
FASEB J. 2020 Aug;34(8):10489-10504
pubmed: 32579290
Proc Natl Acad Sci U S A. 2007 Jun 5;104(23):9876-81
pubmed: 17535922
Biochem J. 2001 Feb 1;353(Pt 3):417-39
pubmed: 11171037
Biomed Environ Sci. 2022 Jul 20;35(7):622-632
pubmed: 35945177
PLoS One. 2018 Nov 27;13(11):e0206883
pubmed: 30481179
Basic Res Cardiol. 2016 Mar;111(2):15
pubmed: 26818679
Cell Biosci. 2022 Aug 6;12(1):123
pubmed: 35933397
J Biol Chem. 1984 Oct 10;259(19):12144-52
pubmed: 6090457
Front Pharmacol. 2018 Jan 22;9:13
pubmed: 29403384
Pflugers Arch. 2002 Sep;444(6):801-9
pubmed: 12355181
Biochim Biophys Acta. 1971 Aug 6;245(1):259-62
pubmed: 4332100
Am J Physiol Heart Circ Physiol. 2012 May 15;302(10):H2008-17
pubmed: 22427521
Am J Physiol Heart Circ Physiol. 2005 Jul;289(1):H30-6
pubmed: 15749746
Clin Cancer Res. 2017 Feb 15;23(4):885-893
pubmed: 27881582
J Biol Chem. 1996 Dec 27;271(52):33561-7
pubmed: 8969222
World J Gastrointest Oncol. 2021 Jul 15;13(7):716-731
pubmed: 34322200
Circ Res. 2005 Dec 9;97(12):1288-95
pubmed: 16293789
J Biol Chem. 2014 Dec 5;289(49):33862-73
pubmed: 25320082
J Biol Chem. 2014 Jan 3;289(1):163-76
pubmed: 24225947
J Physiol. 1996 Oct 15;496 ( Pt 2):575-81
pubmed: 8910239
Biochim Biophys Acta Mol Cell Res. 2019 Jan;1866(1):31-50
pubmed: 30030003