Evidence map›Paper›PMID 32339566›Full record

ArticleJournal of molecular and cellular cardiology2020

Proteomic analysis of the cardiac myocyte secretome reveals extracellular protective functions for the ER stress response.

Erik A Blackwood, Donna J Thuerauf, Miroslava Stastna, Haley Stephens, Zoe Sand, Amber Pentoney, Khalid Azizi, Tobias Jakobi, Jennifer E Van Eyk, Hugo A Katus and 2 more

Open access · hybridAbstract read
In one paragraph

Article in Journal of molecular and cellular cardiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.7field-weighted citation impact, top 18% 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

20 citing papers in PubMed, 25 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. SALVE: prediction of interorgan communication with transcriptome latent space representation.American journal of physiology. Heart and circulatory physiology · 2025
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Proteomics of the heart.Physiological reviews · 2024
    Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Matters of the heart: Cellular sex differences.Journal of molecular and cellular cardiology · 2021
    Review
  18. Article
  19. Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 5 institutions in 3 countries.

Erik A BlackwoodSan Diego State University Heart Institute and the Department of Biology, San Diego State University, San Diego, CA, USA.
Donna J ThueraufSan Diego State University Heart Institute and the Department of Biology, San Diego State University, San Diego, CA, USA.
Miroslava StastnaAdvanced Clinical Biosystems Research Institute, Heart Institute and Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Institute of Analytical Chemistry of the Czech Academy of Sciences, Brno, Czech Republic.
Haley StephensSan Diego State University Heart Institute and the Department of Biology, San Diego State University, San Diego, CA, USA.
Zoe SandSan Diego State University Heart Institute and the Department of Biology, San Diego State University, San Diego, CA, USA.
Amber PentoneySan Diego State University Heart Institute and the Department of Biology, San Diego State University, San Diego, CA, USA.
Khalid AziziSan Diego State University Heart Institute and the Department of Biology, San Diego State University, San Diego, CA, USA.
Tobias JakobiDepartment of Internal Medicine III (Cardiology, Angiology, and Pneumology), Heidelberg University Hospital, Heidelberg, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Germany; Section of Bioinformatics and Systems Cardiology, Klaus Tschira Institute for Integrative Computational Cardiology, Heidelberg University Hospital, Heidelberg, Germany.
Jennifer E Van EykAdvanced Clinical Biosystems Research Institute, Heart Institute and Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Hugo A KatusDepartment of Internal Medicine III (Cardiology, Angiology, and Pneumology), Heidelberg University Hospital, Heidelberg, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Germany.
Christopher C GlembotskiSan Diego State University Heart Institute and the Department of Biology, San Diego State University, San Diego, CA, USA.
Shirin DoroudgarDepartment of Internal Medicine III (Cardiology, Angiology, and Pneumology), Heidelberg University Hospital, Heidelberg, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Germany. Electronic address: shirin.doroudgar@med.uni-heidelberg.de.
San Diego State University · USCedars-Sinai Medical Center · USGerman Centre for Cardiovascular Research · DEHeidelberg University · DEUniversity Hospital Heidelberg · DE

Funding

Surgery, Physiology and ImmunohistopathologyP01HL085577 · NHLBI · SAN DIEGO STATE UNIVERSITY · PI GUSTAFSSON, ASA B. · 2006 to 2017
$18.4M
Protein Chemistry and ProteomicsP01HL112730 · NHLBI · SAN DIEGO STATE UNIVERSITY · PI VAN EYK, JENNIFER E · 2013 to 2017
$12.0M
Role of Unfolded Protein Response in Cardiac ProtectionR01HL075573 · NHLBI · SAN DIEGO STATE UNIVERSITY · PI GLEMBOTSKI, CHRIS · 2004 to 2011
$3.0M
Mitochondrial Turnover in the Human HeartR01HL132075 · NHLBI · CEDARS-SINAI MEDICAL CENTER · PI GOTTLIEB, ROBERTA A., VAN EYK, JENNIFER E · 2017 to 2020
$2.1M
The ER Stress-Induced Selenoprotein, SelenoS, Regulates Proteostasis and Cardiac HypertrophyR01HL149931 · NHLBI · UNIVERSITY OF ARIZONA · PI GLEMBOTSKI, CHRIS · 2020 to 2023
$1.7M
Harnessing the Adaptive ER Stress Response in Myocardial IschemiaR01HL135893 · NHLBI · UNIVERSITY OF ARIZONA · PI GLEMBOTSKI, CHRIS · 2017 to 2020
$1.5M
ATF6 is Required for ANP Secretion from the HeartR01HL141463 · NHLBI · UNIVERSITY OF ARIZONA · PI GLEMBOTSKI, CHRIS · 2019 to 2022
$1.5M
Roles for ER Stress Inducible Cardiomyokines in the heartR01HL104535 · NHLBI · SAN DIEGO STATE UNIVERSITY · PI GLEMBOTSKI, CHRIS · 2010 to 2013
$1.5M
The Adaptive Cardiac Sensor, ATF6, Regulates ANP Secretion and Decreases Hypertensive StressF31HL140850 · NHLBI · SAN DIEGO STATE UNIVERSITY · PI BLACKWOOD, ERIK · 2018 to 2020
$69k
CALPONIN AND DIFFERENTIATED VASCULAR SMOOTH MUSCLEF32HL010026 · NHLBI · UNIVERSITY OF NEVADA RENO · PI LEINWEBER, BARBARA D · 1998 to 2000
$38k
NHLBI NIH HHS F31 HL140850NHLBI NIH HHS F32 HL010026NHLBI NIH HHS P01 HL085577NHLBI NIH HHS P01 HL112730NHLBI NIH HHS R01 HL075573NHLBI NIH HHS R01 HL104535NHLBI NIH HHS R01 HL132075NHLBI NIH HHS R01 HL135893NHLBI NIH HHS R01 HL141463NHLBI NIH HHS R01 HL149931
6 · The paper itself

Abstract

The effects of ER stress on protein secretion by cardiac myocytes are not well understood. In this study, the ER stressor thapsigargin (TG), which depletes ER calcium, induced death of cultured neonatal rat ventricular myocytes (NRVMs) in high media volume but fostered protection in low media volume. In contrast, another ER stressor, tunicamycin (TM), a protein glycosylation inhibitor, induced NRVM death in all media volumes, suggesting that protective proteins were secreted in response to TG but not TM. Proteomic analyses of TG- and TM-conditioned media showed that the secretion of most proteins was inhibited by TG and TM; however, secretion of several ER-resident proteins, including GRP78 was increased by TG but not TM. Simulated ischemia, which decreases ER/SR calcium also increased secretion of these proteins. Mechanistically, secreted GRP78 was shown to enhance survival of NRVMs by collaborating with a cell-surface protein, CRIPTO, to activate protective AKT signaling and to inhibit death-promoting SMAD2 signaling. Thus, proteins secreted during ER stress mediated by ER calcium depletion can enhance cardiac myocyte viability.

Indexed as

Endoplasmic Reticulum StressProteomeProteomicsAnimalsApoptosisAutocrine CommunicationBiomarkersCalciumCalcium SignalingCells, CulturedCell SurvivalDisease SusceptibilityEndoplasmic Reticulum Chaperone BiPEpidermal Growth FactorMembrane GlycoproteinsMiceBiomarkersCalciumEndoplasmic Reticulum Chaperone BiPEpidermal Growth FactorHspa5 protein, mouseMembrane GlycoproteinsNeoplasm ProteinsProteomeTdgf1 protein, mouseThapsigarginCardiac myocyte deathCardiokineCardioprotectionER stressHeart failureProteostasis

Identifiers

PMID32339566
PMCPMC8597053
OpenAlexW3019386081

What OpenQuestion holds

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LicenceCC BY-NC-ND
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.