Evidence map›Paper›PMID 24699520›Full record

ArticleBritish journal of anaesthesia2014

Isoflurane induces endoplasmic reticulum stress and caspase activation through ryanodine receptors.

H Wang, Y Dong, J Zhang, Z Xu, G Wang, C A Swain, Y Zhang, Z Xie

Open access · bronzeAbstract read
In one paragraph

Article in British journal of anaesthesia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

31 citing papers in PubMed, 57 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Review
  6. Ultrasound-Assisted HAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  7. Article
  8. Article
  9. Article
  10. Ryanodine receptor RyR1-mediated elevation of CaJournal of animal science and biotechnology · 2022
    Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Impact of general anaesthesia on endoplasmic reticulum stress: propofolInternational journal of medical sciences · 2019
    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

8 authors at 4 institutions in 2 countries.

H WangGeriatric Anaesthesia Research Unit, Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, 149 13th St., Room 4310, Charlestown, MA 02129-2060, USA Department of Anaesthesiology, Tianjin Medical University General Hospital, Tianjin Research Institute of Anaesthesiology, Tianjin 300052, PR China.
Y DongGeriatric Anaesthesia Research Unit, Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, 149 13th St., Room 4310, Charlestown, MA 02129-2060, USA.
J ZhangGeriatric Anaesthesia Research Unit, Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, 149 13th St., Room 4310, Charlestown, MA 02129-2060, USA Department of Anaesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
Z XuGeriatric Anaesthesia Research Unit, Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, 149 13th St., Room 4310, Charlestown, MA 02129-2060, USA.
G WangDepartment of Anaesthesiology, Tianjin Medical University General Hospital, Tianjin Research Institute of Anaesthesiology, Tianjin 300052, PR China.
C A SwainGeriatric Anaesthesia Research Unit, Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, 149 13th St., Room 4310, Charlestown, MA 02129-2060, USA.
Y ZhangGeriatric Anaesthesia Research Unit, Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, 149 13th St., Room 4310, Charlestown, MA 02129-2060, USA.
Z XieGeriatric Anaesthesia Research Unit, Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, 149 13th St., Room 4310, Charlestown, MA 02129-2060, USA zxie@partners.org.
Massachusetts General Hospital · USHarvard University · USTianjin Medical University General Hospital · CNHuazhong University of Science and Technology · CN

Funding

Pathogenesis of Postoperative Cognitive DysfunctionR01AG041274 · NIA · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI Zhongcong Xie, Guang Yang · 2012 to 2026
$6.7M
General Anesthesia and Alzheimer's Disease NeuropathogenesisR01GM088801 · NIGMS · MASSACHUSETTS GENERAL HOSPITAL · PI XIE, ZHONGCONG · 2009 to 2017
$3.1M
The Role of Alzheimer's-associated Abeta in POD and POCDR21AG038994 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI XIE, ZHONGCONG · 2011 to 2012
$412k
Role of Anesthetic Isoflurane in Alzheimer's Disease: In Vivo InvestigationR21AG029856 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI XIE, ZHONGCONG · 2008 to 2009
$408k
NIA NIH HHS R01 AG041274NIA NIH HHS R21 AG029856NIA NIH HHS R21AG029856NIA NIH HHS R21 AG038994NIA NIH HHS R21AG038994NIGMS NIH HHS R01 GM088801
6 · The paper itself

Abstract

backgroundIsoflurane has been reported to induce caspase-3 activation, which may induce neurotoxicity and contribute to the pathogenesis of Alzheimer's disease. However, the underlying mechanism is largely unknown, especially whether or not isoflurane can induce ryanodine receptors (RyRs)-associated endoplasmic reticulum (ER) stress, leading to caspase-3 activation. We therefore assessed the effects of isoflurane on RyRs-associated ER stress.

methodsWe treated primary neurones from wild-type (C57BL/6J) mice with 1% and 2% isoflurane for 1, 3, or 6 h. We then measured levels of C/EBP homologous protein (CHOP) and caspase-12, two ER stress markers, using immunocytochemistry staining and western blotting analysis. Dantrolene (5 μM), the antagonist of RyRs, was used to investigate the role of RyRs in the isoflurane-induced ER stress and caspase-3 activation.

resultsIsoflurane 2% for 6 h treatment increased the levels of CHOP (876% vs 100%, P=0.00009) and caspase-12 (276% vs 100%, P=0.006), and induced caspase-3 activation in the neurones. The administration of 2% isoflurane for 3 h (shorter duration), however, only increased the levels of CHOP (309% vs 100%, P=0.003) and caspase-12 (266% vs 100%, P=0.001), without causing caspase-3 activation. The isoflurane-induced ER stress (CHOP: F=16.64, P=0.0022; caspase-12: F=6.13, P=0.0383) and caspase-3 activation (F=32.06, P=0.0005) were attenuated by the dantrolene treatment.

conclusionsThese data imply that isoflurane might induce caspase-3 activation by causing ER stress through RyRs, and dantrolene could attenuate the isoflurane-induced ER stress and caspase-3 activation. Further investigations of the potential neurotoxicity of isoflurane are needed.

Indexed as

ActinsAnesthetics, InhalationAnimalsBlotting, WesternCaspase 12Caspase 3CaspasesDantroleneEndoplasmic Reticulum StressEnzyme ActivationImmunohistochemistryIsofluraneMiceMice, Inbred C57BLMuscle Relaxants, CentralNeuronsActinsAnesthetics, InhalationCaspase 12Caspase 3CaspasesDantroleneDdit3 protein, mouseIsofluraneMuscle Relaxants, CentralRyanodine Receptor Calcium Release ChannelTranscription Factor CHOPendoplasmic reticuluminhalation anaesthetics, isofluranereceptors, ryanodine

Identifiers

PMID24699520
PMCPMC4166888
OpenAlexW2141043038

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.