ArticleProceedings of the National Academy of Sciences of the United States of America2004
Cardiac-specific overexpression of sarcolipin inhibits sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA2a) activity and impairs cardiac function in mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
55 citing papers in PubMed, 2 syntheses or guidelines pooled it, 109 citations in OpenAlex.
- Pooled it
- Pooled it
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- Reduced Graphene-Oxide-Doped Elastic Biodegradable Polyurethane Fibers for Cardiomyocyte Maturation.ACS biomaterials science & engineering · 2024Article
- Perimenopause Decreases SERCA2a Activity in the Hearts of a Mouse Model of Ovarian Failure.Biomolecules · 2024Article
- Identification of hub genes and potential ceRNA networks of diabetic cardiomyopathy.Scientific reports · 2023Article
- Neprilysins regulate muscle contraction and heart function via cleavage of SERCA-inhibitory micropeptides.Nature communications · 2022Article
- NBP Relieves Cardiac Injury and Reduce Oxidative Stress and Cell Apoptosis in Heart Failure Mice by Activating Nrf2/HO-1/CaEvidence-based complementary and alternative medicine : eCAM · 2022Article
- Structure-function relationships and modifications of cardiac sarcoplasmic reticulum Ca2+-transport.Physiological research · 2021Review
- Altered Electrical, Biomolecular, and Immunologic Phenotypes in a Novel Patient-Derived Stem Cell Model of Desmoglein-2 Mutant ARVC.Journal of clinical medicine · 2021Article
- Article
- The Dipeptidyl Peptidase-4 Inhibitor Linagliptin Directly Enhances the Contractile Recovery of Mouse Hearts at a Concentration Equivalent to that Achieved with Standard Dosing in Humans.International journal of molecular sciences · 2020Article
- Activation of sarcolipin expression and altered calcium cycling inBiochemistry and biophysics reports · 2020Article
- SERCA2a: a key protein in the CaHeart failure reviews · 2020Review
- Primary Active CaCold Spring Harbor perspectives in biology · 2020Review
- Long-term cardiovascular disorders in the STOX1 mouse model of preeclampsia.Scientific reports · 2019Article
- Simultaneous imaging of local calcium and single sarcomere length in rat neonatal cardiomyocytes using yellow Cameleon-Nano140.The Journal of general physiology · 2016Article
- Phospholamban and sarcolipin: Are they functionally redundant or distinct regulators of the Sarco(Endo)Plasmic Reticulum Calcium ATPase?Journal of molecular and cellular cardiology · 2016Review
- Effect of substrate mechanics on cardiomyocyte maturation and growth.Tissue engineering. Part B, Reviews · 2015Review
- Identification of Region-Specific Myocardial Gene Expression Patterns in a Chronic Swine Model of Repaired Tetralogy of Fallot.PloS one · 2015Article
Corrections and comments
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Authors and funding
19 authors at 1 institution in 1 country.
Funding
Abstract
Sarcolipin (SLN) inhibits the cardiac sarco(endo)plasmic reticulum Ca(2+) ATPase (SERCA2a) by direct binding and is superinhibitory if it binds through phospholamban (PLN). To determine whether overexpression of SLN in the heart might impair cardiac function, transgenic (TG) mice were generated with cardiac-specific overexpression of NF-SLN (SLN tagged at its N terminus with the FLAG epitope). The level of NF-SLN expression (the NF-SLN/PLN expression ratio) was equivalent to that which induces profound superinhibition when coexpressed with PLN and SERCA2a in HEK-293 cells. In TG hearts, the apparent affinity of SERCA2a for Ca(2+) was decreased compared with non-TG littermate control hearts. Invasive hemodynamic and echocardiographic analyses revealed impaired cardiac contractility and ventricular hypertrophy in TG mice. Basal PLN phosphorylation was reduced. In isolated papillary muscle subjected to isometric tension, peak amplitudes of Ca(2+) transients and peak tensions were reduced, whereas decay times of Ca(2+) transients and relaxation times of tension were increased in TG mice. Isoproterenol largely restored contractility in papillary muscle and stimulated PLN phosphorylation to wild-type levels in intact hearts. No compensatory changes in expression of SERCA2a, PLN, ryanodine receptor, and calsequestrin were observed in TG hearts. Coimmunoprecipitation indicated that overexpressed NF-SLN was bound to both SERCA2a and PLN, forming a ternary complex. These data suggest that NF-SLN overexpression inhibits SERCA2a through stabilization of SERCA2a-PLN interaction in the absence of PLN phosphorylation and through the inhibition of PLN phosphorylation. Inhibition of SERCA2a impairs contractility and calcium cycling, but responsiveness to beta-adrenergic agonists may prevent progression to heart failure.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.