Evidence map›Paper›PMID 30786847›Full record

ArticleCirculation research2019

Role of SIRT1 in Modulating Acetylation of the Sarco-Endoplasmic Reticulum Ca

Przemek A Gorski, Seung Pil Jang, Dongtak Jeong, Ahyoung Lee, Philyoung Lee, Jae Gyun Oh, Vadim Chepurko, Dong Kwon Yang, Tae Hwan Kwak, Soo Hyun Eom and 12 more

Erratum issuedOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
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Article in Circulation research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 98 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
98citing papers in PubMed, 1 pooled it
8.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

98 citing papers in PubMed, 1 synthesis or guideline pooled it, 129 citations in OpenAlex.

  1. Pooled it
  2. Research progress on lysine acetylation (Review).International journal of molecular medicine · 2026
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38 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors at 7 institutions in 4 countries.

Przemek A GorskiFrom the Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York (P.A.G., D.J., A.L., P.L., J.G.O., V.C., R.J.H., C.K.).
Seung Pil JangCollege of Life Sciences, Gwangju Institute of Science and Technology, Korea (S.P.J., D.K.Y., S.H.E., Z.-Y.P., Y.J.Y., D.H.K., W.J.P.).
Dongtak JeongFrom the Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York (P.A.G., D.J., A.L., P.L., J.G.O., V.C., R.J.H., C.K.).
Ahyoung LeeFrom the Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York (P.A.G., D.J., A.L., P.L., J.G.O., V.C., R.J.H., C.K.).
Philyoung LeeFrom the Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York (P.A.G., D.J., A.L., P.L., J.G.O., V.C., R.J.H., C.K.).
Jae Gyun OhFrom the Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York (P.A.G., D.J., A.L., P.L., J.G.O., V.C., R.J.H., C.K.).
Vadim ChepurkoFrom the Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York (P.A.G., D.J., A.L., P.L., J.G.O., V.C., R.J.H., C.K.).
Dong Kwon YangCollege of Life Sciences, Gwangju Institute of Science and Technology, Korea (S.P.J., D.K.Y., S.H.E., Z.-Y.P., Y.J.Y., D.H.K., W.J.P.).
Tae Hwan KwakNADIAN BIO Ltd, Iksan, Jeonbuk, Korea (T.H.K.).
Soo Hyun EomCollege of Life Sciences, Gwangju Institute of Science and Technology, Korea (S.P.J., D.K.Y., S.H.E., Z.-Y.P., Y.J.Y., D.H.K., W.J.P.).
Zee-Yong ParkCollege of Life Sciences, Gwangju Institute of Science and Technology, Korea (S.P.J., D.K.Y., S.H.E., Z.-Y.P., Y.J.Y., D.H.K., W.J.P.).
Yung Joon YooCollege of Life Sciences, Gwangju Institute of Science and Technology, Korea (S.P.J., D.K.Y., S.H.E., Z.-Y.P., Y.J.Y., D.H.K., W.J.P.).
Do Han KimCollege of Life Sciences, Gwangju Institute of Science and Technology, Korea (S.P.J., D.K.Y., S.H.E., Z.-Y.P., Y.J.Y., D.H.K., W.J.P.).
Hyun KookBasic Research Laboratory, Chonnam National University Medical School, Hwasun-gun, Jeollanam-do, Korea (H.K.).
Yoichi SunagawaDivision of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Japan (Y.S., T.M.).
Tatsuya MorimotoDivision of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Japan (Y.S., T.M.).
Koji HasegawaDivision of Translational Research, Clinical Research Institute, Kyoto Medical Center, Japan (K.H.).
Junichi SadoshimaDepartment of Cell Biology and Molecular Medicine, Rutgers New Jersey Medical School, Newark (J.S.).
Peter VangheluweDepartment of Cellular and Molecular Medicine, KU Leuven, Belgium (P.V.)
Roger J HajjarFrom the Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York (P.A.G., D.J., A.L., P.L., J.G.O., V.C., R.J.H., C.K.).
Woo Jin ParkCollege of Life Sciences, Gwangju Institute of Science and Technology, Korea (S.P.J., D.K.Y., S.H.E., Z.-Y.P., Y.J.Y., D.H.K., W.J.P.).
Changwon KhoFrom the Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York (P.A.G., D.J., A.L., P.L., J.G.O., V.C., R.J.H., C.K.).
Icahn School of Medicine at Mount Sinai · USGwangju Institute of Science and Technology · KRUniversity of Shizuoka · JPChonnam National University · KRKU Leuven · BEKyoto Medical Center · JPRutgers, The State University of New Jersey · US

Funding

TRAINING PROGRAM IN MOLECULAR AND CELLULAR CARDIOLOGYT32HL007824 · NHLBI · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI GELB, BRUCE D · 1995 to 2022
$8.6M
TRIP: Targeted Gene Therapy for the Treatment of Heart FailureP50HL112324 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI ASCHEIM, DEBORAH DAVIS, HAJJAR, ROGER J. · 2012 to 2014
$6.4M
SUMO1 and SERCA2a FunctionR01HL117505 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI WEBER, THOMAS · 2013 to 2020
$3.4M
Anti-AAV Antibodies as an Obstacle to Cardiac AAV Gene TherapyR01HL131404 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI WEBER, THOMAS · 2016 to 2019
$3.3M
Calcium Pump Activators for Heart Failure TherapyR01HL129814 · NHLBI · UNIVERSITY OF MINNESOTA · PI THOMAS, DAVID D · 2015 to 2018
$3.2M
Targeting Abnormal Calcium Cycling Using Novel Gene Therapy VectorsR01HL119046 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI AKAR, FADI GABRIEL, HAJJAR, ROGER J. · 2014 to 2017
$2.9M
Treating Ventricle and Valve: New Synergies for Ischemic LV Remodeling with MRR01HL128099 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI AKAR, FADI GABRIEL, LEVINE, ROBERT A · 2016 to 2019
$2.8M
Small Molecule Therapy for the Treatment of Heart FailureR42HL132684 · NHLBI · SUMOCOR, LLC · PI HAJJAR, ROGER J. · 2017 to 2018
$819k
The Role of Post-translational Acetylation in SERCA2a-related Cardiac DysfunctionR00HL116645 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI KHO, CHANGWON · 2015 to 2017
$747k
The role of post-translational acetylation in SERCA2a-related cardiac dysfunctionK99HL116645 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI KHO, CHANGWON · 2013 to 2014
$260k
Novel SUMO Activators for the Treatment of Duchenne Muscular Dystrophy-Associated Heart FailureR43HL144223 · NHLBI · SUMOCOR, LLC · PI LEE, AHYOUNG · 2018 to 2018
$241k
American Heart Association-American Stroke Association 17POST33410877American Heart Association-American Stroke Association 18TPA34170460CIHRNHLBI NIH HHS K99 HL116645NHLBI NIH HHS P50 HL112324NHLBI NIH HHS R00 HL116645NHLBI NIH HHS R01 HL117505NHLBI NIH HHS R01 HL119046NHLBI NIH HHS R01 HL128099NHLBI NIH HHS R01 HL129814NHLBI NIH HHS R01 HL131404NHLBI NIH HHS R42 HL132684NHLBI NIH HHS R43 HL144223NHLBI NIH HHS T32 HL007824
6 · The paper itself

Abstract

rationaleSERCA2a, sarco-endoplasmic reticulum Ca

objectiveIn this study, we aim to assess the role of lysine acetylation on SERCA2a function and determine whether inhibition of lysine acetylation can improve cardiac function in the setting of heart failure. METHODS AND

resultsThe acetylation of SERCA2a was significantly increased in failing hearts of humans, mice, and pigs, which is associated with the reduced level of SIRT1 (sirtuin 1), a class III histone deacetylase. Downregulation of SIRT1 increased the SERCA2a acetylation, which in turn led to SERCA2a dysfunction and cardiac defects at baseline. In contrast, pharmacological activation of SIRT1 reduced the SERCA2a acetylation, which was accompanied by recovery of SERCA2a function and cardiac defects in failing hearts. Lysine 492 (K492) was of critical importance for the regulation of SERCA2a activity via acetylation. Acetylation at K492 significantly reduced the SERCA2a activity, presumably through interfering with the binding of ATP to SERCA2a. In failing hearts, acetylation at K492 appeared to be mediated by p300 (histone acetyltransferase p300), a histone acetyltransferase.

conclusionsThese results indicate that acetylation/deacetylation at K492, which is regulated by SIRT1 and p300, is critical for the regulation of SERCA2a activity in hearts. Pharmacological activation of SIRT1 can restore SERCA2a activity through deacetylation at K492. These findings might provide a novel strategy for the treatment of heart failure.

Indexed as

AcetylationAdenosine TriphosphateAnimalsCell LineCells, CulturedE1A-Associated p300 ProteinHeart FailureHumansLysineMaleMice, Inbred C57BLMice, KnockoutMice, TransgenicMyocytes, CardiacProtein Processing, Post-TranslationalSarcoplasmic Reticulum Calcium-Transporting ATPasesAdenosine TriphosphateE1A-Associated p300 ProteinEP300 protein, humanLysineSarcoplasmic Reticulum Calcium-Transporting ATPasesSIRT1 protein, humanSirtuin 1acetylationendoplasmic reticulumheart failurelysinemice

Identifiers

PMID30786847
PMCPMC6483854
OpenAlexW2917617036

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.