Evidence map›Paper›PMID 23275378›Full record

ArticleThe Journal of biological chemistry2013

Molecular mechanisms underlying the apoptotic effect of KCNB1 K+ channel oxidation.

Xilong Wu, Berenice Hernandez-Enriquez, Michelle Banas, Robin Xu, Federico Sesti

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
1.9field-weighted citation impact, top 15% 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

28 citing papers in PubMed, 41 citations in OpenAlex.

  1. The Polypharmacological Effects of Cannabidiol.Molecules (Basel, Switzerland) · 2023
    Review
  2. Article
  3. Review
  4. Review
  5. Antagonistic roles of Ras-MAPK and Akt signaling in integrin-KFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022
    Article
  6. Review
  7. Article
  8. Tyrosine Phosphorylation of the KInternational journal of molecular sciences · 2020
    Article
  9. Review
  10. Voltage-Gated Potassium Channels as Regulators of Cell Death.Frontiers in cell and developmental biology · 2020
    Review
  11. Complexes formed with integrin-α5 and KCNB1 potassium channel wild type or epilepsy-susceptibility variants modulate cellular plasticityFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019
    Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Oxidation of KCNB1 Potassium Channels Causes Neurotoxicity and Cognitive Impairment in a Mouse Model of Traumatic Brain Injury.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016
    Article
  19. Alcohol Regulates BK Surface Expression via Wnt/β-Catenin Signaling.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016
    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

5 authors at 1 institution in 1 country.

Xilong WuUniversity of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Department of Neuroscience and Cell Biology, 683 Hoes Ln. W., Piscataway, New Jersey 08854, USA.
Berenice Hernandez-Enriquez
Michelle Banas
Robin Xu
Federico Sesti
Rutgers, The State University of New Jersey · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Potassium (K(+)) channels are targets of reactive oxygen species in the aging nervous system. KCNB1 (formerly Kv2.1), a voltage-gated K(+) channel abundantly expressed in the cortex and hippocampus, is oxidized in the brains of aging mice and of the triple transgenic 3xTg-AD mouse model of Alzheimer's disease. KCNB1 oxidation acts to enhance apoptosis in mammalian cell lines, whereas a KCNB1 variant resistant to oxidative modification, C73A-KCNB1, is cytoprotective. Here we investigated the molecular mechanisms through which oxidized KCNB1 channels promote apoptosis. Biochemical evidence showed that oxidized KCNB1 channels, which form oligomers held together by disulfide bridges involving Cys-73, accumulated in the plasma membrane as a result of defective endocytosis. In contrast, C73A-mutant channels, which do not oligomerize, were normally internalized. KCNB1 channels localize in lipid rafts, and their internalization was dynamin 2-dependent. Accordingly, cholesterol supplementation reduced apoptosis promoted by oxidation of KCNB1. In contrast, cholesterol depletion exacerbated apoptotic death in a KCNB1-independent fashion. Inhibition of raft-associating c-Src tyrosine kinase and downstream JNK kinase by pharmacological and molecular means suppressed the pro-apoptotic effect of KCNB1 oxidation. Together, these data suggest that the accumulation of KCNB1 oligomers in the membrane disrupts planar lipid raft integrity and causes apoptosis via activating the c-Src/JNK signaling pathway.

Indexed as

ApoptosisMAP Kinase Signaling SystemProtein MultimerizationAgingAlzheimer DiseaseAmino Acid SubstitutionAnimalsCell Line, TumorCSK Tyrosine-Protein KinaseDisease Models, AnimalDynamin IIMAP Kinase Kinase 4Membrane MicrodomainsMiceMice, TransgenicMutation, MissenseCSK Tyrosine-Protein KinaseDynamin IIKcnb1 protein, mouseMAP Kinase Kinase 4Shab Potassium Channelssrc-Family Kinases

Identifiers

PMID23275378
PMCPMC3567663
OpenAlexW1997135806

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.