Evidence map›Paper›PMID 30908935›Full record

ArticleAmerican journal of physiology. Lung cellular and molecular physiology2019

A nonapoptotic endothelial barrier-protective role for caspase-3.

Karthik Suresh, Kathleen Carino, Laura Johnston, Laura Servinsky, Carolyn E Machamer, Todd M Kolb, Hong Lam, Steven M Dudek, Steven S An, Madhavi J Rane and 2 more

Open access · greenAbstract read
In one paragraph

Article in American journal of physiology. Lung cellular and molecular physiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

22 citing papers in PubMed, 36 citations in OpenAlex.

  1. Article
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  3. Article
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  6. Review
  7. Article
  8. MK2 nonenzymatically promotes nuclear translocation of caspase-3 and resultant apoptosis.American journal of physiology. Lung cellular and molecular physiology · 2023
    Article
  9. Article
  10. Structural Characteristics ofFoods (Basel, Switzerland) · 2022
    Article
  11. 'Youthful' phenotype of c-KitCellular and molecular life sciences : CMLS · 2022
    Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Contribution of cell death signaling to blood vessel formation.Cellular and molecular life sciences : CMLS · 2021
    Review
  18. Article
  19. KD025 Shifts Pulmonary Endothelial Cell Bioenergetics and Decreases Baseline Lung Permeability.American journal of respiratory cell and molecular biology · 2020
    Article
  20. Article
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 3 institutions in 1 country.

Karthik SureshDepartment of Medicine, Johns Hopkins University School of Medicine , Baltimore, Maryland.
Kathleen CarinoDepartment of Medicine, Johns Hopkins University School of Medicine , Baltimore, Maryland.
Laura JohnstonDepartment of Medicine, Johns Hopkins University School of Medicine , Baltimore, Maryland.
Laura ServinskyDepartment of Medicine, Johns Hopkins University School of Medicine , Baltimore, Maryland.
Carolyn E MachamerDepartment of Cell Biology, Johns Hopkins University School of Medicine , Baltimore, Maryland.
Todd M KolbDepartment of Medicine, Johns Hopkins University School of Medicine , Baltimore, Maryland.ORCID 0000-0003-0524-7400
Hong LamDepartment of Environmental Health and Engineering, Johns Hopkins University School of Public Health , Baltimore, Maryland.
Steven M DudekDepartment of Medicine, College of Medicine, University of Illinois at Chicago , Chicago, Illinois.
Steven S AnDepartment of Environmental Health and Engineering, Johns Hopkins University School of Public Health , Baltimore, Maryland.
Madhavi J RaneDepartment of Medicine, School of Medicine, University of Louisville , Louisville, Kentucky.
Larissa A ShimodaDepartment of Medicine, Johns Hopkins University School of Medicine , Baltimore, Maryland.
Mahendra DamarlaDepartment of Medicine, Johns Hopkins University School of Medicine , Baltimore, Maryland.
Johns Hopkins University · USUniversity of Illinois Chicago · USUniversity of Louisville · US

Funding

Targeting Divergent Roles of Caspase 3 to Promote Endothelial Barrier IntegrityR01HL133413 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI DAMARLA, MAHENDRA · 2016 to 2020
$2.0M
Metabolic regulation of Ca2+ entry and endothelial-mesenchymal transition in pulmonary arterial hypertensionR01HL151530 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI SURESH, KARTHIK · 2021 to 2025
$2.0M
ROS-induced endothelial dysfunction in pulmonary arterial hypertensionK08HL132055 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI SURESH, KARTHIK · 2017 to 2021
$828k
NHLBI NIH HHS K08 HL132055NHLBI NIH HHS R01 HL133413NHLBI NIH HHS R01 HL151530
6 · The paper itself

Abstract

Noncanonical roles for caspase-3 are emerging in the fields of cancer and developmental biology. However, little is known of nonapoptotic functions of caspase-3 in most cell types. We have recently demonstrated a disassociation between caspase-3 activation and execution of apoptosis with accompanying cytoplasmic caspase-3 sequestration and preserved endothelial barrier function. Therefore, we tested the hypothesis that nonapoptotic caspase-3 activation promotes endothelial barrier integrity. Human lung microvascular endothelial cells were exposed to thrombin, a nonapoptotic stimulus, and endothelial barrier function was assessed using electric cell-substrate impedance sensing. Actin cytoskeletal rearrangement and paracellular gap formation were assessed using phalloidin staining. Cell stiffness was evaluated using magnetic twisting cytometry. In addition, cell lysates were harvested for protein analyses. Caspase-3 was inhibited pharmacologically with pan-caspase and a caspase-3-specific inhibitor. Molecular inhibition of caspase-3 was achieved using RNA interference. Cells exposed to thrombin exhibited a cytoplasmic activation of caspase-3 with transient and nonapoptotic decrease in endothelial barrier function as measured by a drop in electrical resistance followed by a rapid recovery. Inhibition of caspases led to a more pronounced and rapid drop in thrombin-induced endothelial barrier function, accompanied by increased endothelial cell stiffness and paracellular gaps. Caspase-3-specific inhibition and caspase-3 knockdown both resulted in more pronounced thrombin-induced endothelial barrier disruption. Taken together, our results suggest cytoplasmic caspase-3 has nonapoptotic functions in human endothelium and can promote endothelial barrier integrity.

Indexed as

Actin CytoskeletonCapillary PermeabilityCaspase 3Cells, CulturedElectric ImpedanceEndothelial CellsEndothelium, VascularHumansLungRespiratory MucosaRNA InterferenceRNA, Small InterferingThrombinTight JunctionsCASP3 protein, humanCaspase 3RNA, Small InterferingThrombinbarrier functioncaspase-3cytoskeletonendotheliumhuman lung microvascular endothelial cellsnonapoptoticthrombin

Identifiers

PMID30908935
PMCPMC6620669
OpenAlexW2934457987

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.