Evidence map›Paper›PMID 32339667›Full record

ArticleNeurochemistry international2020

Kappa opioid receptors internalization is protective against oxygen-glucose deprivation through β-arrestin activation and Akt-mediated signaling pathway.

Jihong Xu, Fang Chen, Shuyan Wang, Nicholas S Akins, Md Imran Hossain, Yi Zhou, Jinxi Huang, Jiafu Ji, Jin Xi, Wenzhen Lin and 3 more

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

Article in Neurochemistry international, 2020. 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
0.3field-weighted citation impact, top 44% 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, 5 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Pharmacokinetics and Pharmacodynamics of Salvinorin A andPharmaceuticals (Basel, Switzerland) · 2021
    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

13 authors at 4 institutions in 2 countries.

Jihong XuDepartment of Anesthesiology, Shenzhen University General Hospital, Shenzhen, China; Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Fang ChenDepartment of Anesthesiology, Shenzhen Children's Hospital, Shenzhen, China; Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Shuyan WangDepartment of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Nicholas S AkinsDepartment of BioMolecular Sciences and Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, Mississippi, USA.
Md Imran HossainDepartment of BioMolecular Sciences and Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, Mississippi, USA.
Yi ZhouDepartment of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Jinxi HuangDepartment of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Jiafu JiDepartment of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Jin XiDepartment of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Wenzhen LinDepartment of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
John GrothusenDepartment of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Hoang V LeDepartment of BioMolecular Sciences and Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, Mississippi, USA.
Renyu LiuDepartment of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: liur@stroke120.org.
University of Pennsylvania · USUniversity of Mississippi · USChildren's Hospital of Philadelphia · USShenzhen University · CN

Funding

Pilot Project ProgramP30GM122733 · NIGMS · UNIVERSITY OF MISSISSIPPI · PI WILLETT, KRISTINE L · 2018 to 2022
$5.3M
Water soluble variants of the human mu opioid receptorR01GM111421 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI LIU, RENYU · 2014 to 2018
$1.7M
NIGMS NIH HHS P30 GM122733NIGMS NIH HHS R01 GM111421
6 · The paper itself

Abstract

Hypoxia induces reversible κ-opioid receptor (KOR) internalization similar to the internalization that is induced by KOR agonists. In the current study, we demonstrate that this KOR internalization is a protective mechanism via the β-arrestin specific pathway in an oxygen-glucose deprivation (OGD) model. Mouse neuroblastoma Neuro2A cells were stably transfected with mouse KOR-tdTomato fusion protein (N2A-mKOR-tdT cells). Various concentrations of salvinorin A (SA), a highly selective KOR agonist, were given in the presence and absence of norbinaltorphimine (norBNI), which is a KOR antagonist, or Dyngo-4a (internalization inhibitor) or API-2 (Akt/Protein kinase B signaling inhibitor-2). Various concentrations of SA and RB-64 (22-thiocyanatosalvinorin A, selective for the G protein signaling pathway) were administered both in normoxic and hypoxic conditions. Autophagosomes and ultrastructural components of cells were observed using transmission electron microscopy (TEM). Cell viability, severity of cell injury, and levels of proteins related to the Akt signaling pathway were evaluated using live cell counting (by Cell Counting Kit-8), the lactic acid dehydrogenase (LDH) release rate, and Western blot analysis, respectively. SA promoted cell survival and attenuated OGD-induced cell injury. The Akt signaling pathway is activated by SA. KOR internalization, when blocked by norBNI or Dyngo-4a, increased LDH release and decreased cell viability under OGD. Treatment with SA significantly inhibited autophagy, and the effects of SA on autophagy were reversed by API-2 pretreatment. RB-64 in a low concentration without β-arrestin recruitment did not reduce LDH release and increase cell viability as observed with SA. KOR internalization through β-arrestin activation is a protective mechanism against OGD. The Akt pathway might play a critical role in modulating these protective effects by inhibiting autophagy.

Indexed as

AnimalsAutophagybeta-ArrestinsCell SurvivalGlucoseMiceNaltrexoneOxygenProto-Oncogene Proteins c-aktReceptors, Opioid, kappaSignal Transductionbeta-ArrestinsGlucoseNaltrexonenorbinaltorphimineOxygenProto-Oncogene Proteins c-aktReceptors, Opioid, kappaCell injuryHypoxiaKappa opioid receptorOxygen-glucose deprivationSalvinorin A

Identifiers

PMID32339667
PMCPMC7321825
OpenAlexW3019007493

What OpenQuestion holds

Textmetadata
LicenceTDM
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.