Evidence map›Paper›PMID 33031913›Full record

ArticleBiochimica et biophysica acta. Molecular and cell biology of lipids2021

Soat1 mediates the mouse strain effects on cholesterol loading-induced endoplasmic reticulum stress and CHOP expression in macrophages.

Mengdie Luo, Emmanuel Opoku, C Alicia Traughber, Qimin Hai, Peggy Robinet, Stela Berisha, Jonathan D Smith

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biochimica et biophysica acta. Molecular and cell biology of lipids, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.7field-weighted citation impact, top 34% 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

4 citing papers in PubMed, 6 citations in OpenAlex.

  1. Review
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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

7 authors at 2 institutions in 2 countries.

Mengdie LuoDepartment of Cardiovascular Medicine, Second Xiangya Hospital, Central South University, Changsha, China; Department of Cardiovascular & Metabolic Sciences, Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA.
Emmanuel OpokuDepartment of Cardiovascular & Metabolic Sciences, Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA.
C Alicia TraughberDepartment of Cardiovascular & Metabolic Sciences, Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA; Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine -Case Western Reserve University, Cleveland, OH, USA.
Qimin HaiDepartment of Cardiovascular & Metabolic Sciences, Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA.
Peggy RobinetDepartment of Cardiovascular & Metabolic Sciences, Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA.
Stela BerishaDepartment of Cardiovascular & Metabolic Sciences, Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA.
Jonathan D SmithDepartment of Cardiovascular & Metabolic Sciences, Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA; Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine -Case Western Reserve University, Cleveland, OH, USA. Electronic address: smithj4@ccf.org.
Cleveland Clinic Lerner College of Medicine · USCentral South University · CN

Funding

Vascular Cell function and AtherosclerosisP01HL029582 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI FOX, PAUL L · 1985 to 2019
$32.0M
NHLBI NIH HHS P01 HL029582
6 · The paper itself

Abstract

We previously demonstrated that AKR vs. DBA/2 mouse bone marrow derived macrophages have higher levels of free cholesterol and lower levels of esterified cholesterol after cholesterol loading, and that AKR, but not DBA/2, macrophages induced C/EBP homologous protein (CHOP) expression after cholesterol loading. We earlier determined that the free and esterified cholesterol level effect is due to a truncation in the sterol O-acyltransferase 1 (Soat1) gene, encoding acetyl-coenzyme A acetyltransferase 1 (ACAT1). Here we examined the mechanism for the differential induction of CHOP by cholesterol loading. CHOP was induced in both strains after incubation with tunicamycin, indicating both strains have competent endoplasmic reticulum stress pathways. CHOP was induced when DBA/2 macrophages were cholesterol loaded in the presence of an ACAT inhibitor, indicating that the difference in free cholesterol levels were responsible for this strain effect. This finding was confirmed in macrophages derived from DBA/2 embryonic stem cells. Cholesterol loading of Soat1 gene edited cells, mimicking the AKR allele, led to increased free cholesterol levels and restored CHOP induction. The upstream pathway of free cholesterol induced endoplasmic reticulum stress was investigated; and, RNA-dependent protein kinase-like endoplasmic reticulum kinase (PERK) and inositol-requiring enzyme 1 α protein kinase (IRE1α) pathways were required for maximal CHOP expression.

Indexed as

AnimalsBone Marrow CellsCholesterolCholesterol EsterseIF-2 KinaseEmbryonic Stem CellsEndoplasmic Reticulum StressEndoribonucleasesFemaleFemurGene Expression RegulationMacrophagesMaleMiceMice, Inbred AKRMice, Inbred DBACholesterolCholesterol EstersDdit3 protein, mouseeIF-2 KinaseEndoribonucleasesErn1 protein, mouseProtein Serine-Threonine KinasesSterol O-Acyltransferasesterol O-acyltransferase 1Transcription Factor CHOPTunicamycinCholesterol metabolismEndoplasmic reticulum stressMacrophage

Identifiers

PMID33031913
PMCPMC7686275
OpenAlexW3092610429

What OpenQuestion holds

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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.