Evidence map›Paper›PMID 26109417›Full record

ArticleDiabetes2015

Removal of Abnormal Myofilament O-GlcNAcylation Restores Ca2+ Sensitivity in Diabetic Cardiac Muscle.

Genaro A Ramirez-Correa, Junfeng Ma, Chad Slawson, Quira Zeidan, Nahyr S Lugo-Fagundo, Mingguo Xu, Xiaoxu Shen, Wei Dong Gao, Viviane Caceres, Khalid Chakir and 6 more

Open access · bronzeAbstract read
In one paragraph

Article in Diabetes, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed
5.1field-weighted citation impact, top 4% 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

55 citing papers in PubMed, 101 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Proteomics of the heart.Physiological reviews · 2024
    Review
  8. Review
  9. Best practices in assessing cardiac proteinAmerican journal of physiology. Heart and circulatory physiology · 2023
    Article
  10. Article
  11. Article
  12. Article
  13. Frontiers in endocrinology · 2023
    Article
  14. Review
  15. Review
  16. Article
  17. Cells · 2022
    Review
  18. Review
  19. Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 3 institutions in 1 country.

Genaro A Ramirez-CorreaDivision of Cardiology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD gramirez@jhmi.edu.
Junfeng MaDepartment of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD.
Chad SlawsonDepartment of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS.
Quira ZeidanDepartment of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD.
Nahyr S Lugo-FagundoDivision of Cardiology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD.
Mingguo XuDivision of Cardiology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD.
Xiaoxu ShenDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
Wei Dong GaoDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
Viviane CaceresDivision of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
Khalid ChakirDivision of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
Lauren DeVineDepartment of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD.
Robert N ColeDepartment of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD.
Luigi MarchionniDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD.
Nazareno PaolocciDivision of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
Gerald W HartDepartment of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD.
Anne M MurphyDivision of Cardiology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD.
Johns Hopkins University · USJohns Hopkins Medicine · USUniversity of Kansas Medical Center · US

Funding

Institute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1M
Shared Resource CoresP01HL107153 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI VAN EYK, JENNIFER E · 2011 to 2017
$16.8M
MOLECULAR PHYSIOLOGY OF MYOCARDIAL TROPONIN I VARIANTSR01HL063038 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI MURPHY, ANNE M · 1999 to 2018
$6.2M
Cytosolic O-Glycosylation and Insulin SignalingR01DK061671 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI HART, GERALD WARREN · 2002 to 2014
$4.0M
Nutrient Regulation of Cell Physiology by O-GlcNAcylationR01GM116891 · NIGMS · UNIVERSITY OF GEORGIA · PI HART, GERALD WARREN · 2016 to 2023
$2.4M
Mechanisms Underlying Mitrochondrial Dysfunction in the Diabetic HeartR01HL091923 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI AKAR, FADI GABRIEL, AON, MIGUEL ANTONIO · 2009 to 2012
$1.9M
Regulation of Globin Gene Switching by O-GlcNAc Post-Translational ModificationR01DK100595 · NIDDK · UNIVERSITY OF KANSAS MEDICAL CENTER · PI PETERSON, KENNETH R, SLAWSON, CHAD ERIC · 2014 to 2016
$788k
Mechanisms of Glucose ToxicityR24DK084949 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI HART, GERALD WARREN, HOKE, AHMET · 2010 to 2010
$492k
NHLBI PROTEOMICS INITIATIVE-N01HV28180-268028180-268028180N01HV028180 · HV · JOHNS HOPKINS UNIVERSITY · PI VAN EYK, JENNIFER E · 2002 to 2006
–
American Heart Association-American Stroke Association 12SDG9140008NCATS NIH HHS UL1 TR001079NHLBI NIH HHS HHSN268201000032CNHLBI NIH HHS P01 HL107153NHLBI NIH HHS R01 HL063038NHLBI NIH HHS R01 HL091923NHLBI NIH HHS R01-HL-091923NIDDK NIH HHS R01 DK061671NIDDK NIH HHS R01 DK100595NIDDK NIH HHS R01-DK100595NIDDK NIH HHS R01-DK-61671NIGMS NIH HHS P20-GM12345NIGMS NIH HHS R01 GM116891
6 · The paper itself

Abstract

Contractile dysfunction and increased deposition of O-linked β-N-acetyl-d-glucosamine (O-GlcNAc) in cardiac proteins are a hallmark of the diabetic heart. However, whether and how this posttranslational alteration contributes to lower cardiac function remains unclear. Using a refined β-elimination/Michael addition with tandem mass tags (TMT)-labeling proteomic technique, we show that CpOGA, a bacterial analog of O-GlcNAcase (OGA) that cleaves O-GlcNAc in vivo, removes site-specific O-GlcNAcylation from myofilaments, restoring Ca(2+) sensitivity in streptozotocin (STZ) diabetic cardiac muscles. We report that in control rat hearts, O-GlcNAc and O-GlcNAc transferase (OGT) are mainly localized at the Z-line, whereas OGA is at the A-band. Conversely, in diabetic hearts O-GlcNAc levels are increased and OGT and OGA delocalized. Consistent changes were found in human diabetic hearts. STZ diabetic hearts display increased physical interactions of OGA with α-actin, tropomyosin, and myosin light chain 1, along with reduced OGT and increased OGA activities. Our study is the first to reveal that specific removal of O-GlcNAcylation restores myofilament response to Ca(2+) in diabetic hearts and that altered O-GlcNAcylation is due to the subcellular redistribution of OGT and OGA rather than to changes in their overall activities. Thus, preventing sarcomeric OGT and OGA displacement represents a new possible strategy for treating diabetic cardiomyopathy.

Indexed as

AcetylglucosamineAnimalsbeta-N-AcetylhexosaminidasesCalciumDiabetes Mellitus, ExperimentalDiabetic CardiomyopathiesGene Expression Regulation, EnzymologicHumansMaleMyocardiumMyofibrilsRatsRats, Sprague-DawleySarcomeresAcetylglucosaminebeta-N-AcetylhexosaminidasesCalcium

Identifiers

PMID26109417
PMCPMC4587639
OpenAlexW2109282106

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.