Evidence map›Paper›PMID 27387989›Full record

ArticleStroke2016

70-kDa Heat Shock Protein Downregulates Dynamin in Experimental Stroke: A New Therapeutic Target?

Jong Youl Kim, Nuri Kim, Zhen Zheng, Jong Eun Lee, Midori A Yenari

Open access · bronzeAbstract read
In one paragraph

Article in Stroke, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 1 pooled it
3.7field-weighted citation impact, top 7% 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, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
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  5. Article
  6. Review
  7. Article
  8. Article
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  10. Review
  11. Triggering receptor expressed on myeloid cells-2 expression in the brain is required for maximal phagocytic activity and improved neurological outcomes following experimental stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2019
    Article
  12. Article
  13. Heat-Shock Proteins in Neuroinflammation.Frontiers in pharmacology · 2019
    Review
  14. Review
  15. The Ethanolic Extract ofFrontiers in pharmacology · 2019
    Article
  16. Review
  17. Review
  18. Article
  19. Danger signals in stroke and their role on microglia activation after ischemia.Therapeutic advances in neurological disorders · 2018
    Review
  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.

Jong Youl KimFrom the Department of Neurology, UCSF and the SF Veterans Affairs Medical Center, CA (J.Y.K., N.K., Z.Z., M.A.Y.); and Department of Anatomy, BK21 Plus Project for Medical Science and Brain Research Institute, Yonsei University College of Medicine, Seoul, ROK (J.E.L.).
Nuri KimFrom the Department of Neurology, UCSF and the SF Veterans Affairs Medical Center, CA (J.Y.K., N.K., Z.Z., M.A.Y.); and Department of Anatomy, BK21 Plus Project for Medical Science and Brain Research Institute, Yonsei University College of Medicine, Seoul, ROK (J.E.L.).
Zhen ZhengFrom the Department of Neurology, UCSF and the SF Veterans Affairs Medical Center, CA (J.Y.K., N.K., Z.Z., M.A.Y.); and Department of Anatomy, BK21 Plus Project for Medical Science and Brain Research Institute, Yonsei University College of Medicine, Seoul, ROK (J.E.L.).
Jong Eun LeeFrom the Department of Neurology, UCSF and the SF Veterans Affairs Medical Center, CA (J.Y.K., N.K., Z.Z., M.A.Y.); and Department of Anatomy, BK21 Plus Project for Medical Science and Brain Research Institute, Yonsei University College of Medicine, Seoul, ROK (J.E.L.).
Midori A YenariFrom the Department of Neurology, UCSF and the SF Veterans Affairs Medical Center, CA (J.Y.K., N.K., Z.Z., M.A.Y.); and Department of Anatomy, BK21 Plus Project for Medical Science and Brain Research Institute, Yonsei University College of Medicine, Seoul, ROK (J.E.L.). yenari@alum.mit.edu.
Veterans Health Administration · US

Funding

Inflammatory Mechanisms in Cerebral IschemiaR01NS040516 · NINDS · STANFORD UNIVERSITY · PI YENARI, MIDORI A · 2001 to 2014
$4.6M
Heat shock proteins in brain ischemia and strokeI01BX000589 · VA · VETERANS AFFAIRS MED CTR SAN FRANCISCO · PI YENARI, MIDORI A · 2011 to 2019
–
BLRD VA I01 BX000589NINDS NIH HHS R01 NS040516
6 · The paper itself

Abstract

background and purposeThe 70-kDa heat shock protein (Hsp70) protects brain cells in models of cerebral ischemia. Proteomic screening of mice subjected to middle cerebral artery occlusion identified dynamin as a major downregulated protein in Hsp70-overexpressing mice (Hsp70 transgenic mice). Dynamin-1 is expressed in neurons and participates in neurotransmission, but also transports the death receptor Fas to the cell surface, where it can be bound by its ligand and lead to apoptosis.

methodsMice were subjected to distal middle cerebral artery occlusion. Neuro-2a cells were subjected to oxygen glucose deprivation. Hsp70 transgenic and Hsp70-deficient (Hsp70 knockout) mice were compared with wild-type mice for histological and behavioral outcomes. Some mice and neuro-2a cell cultures were given dynasore, a dynamin inhibitor.

resultsHsp70 transgenic mice had better outcomes, whereas Hsp70 knockout mice had worse outcomes compared with wild-type mice. This correlated with decreased and increased dynamin expression, respectively. Dynamin colocalized to neurons and Fas, with higher Fas levels and increased caspase-8 expression. Hsp70 induction in neuro-2a cells was protected from oxygen glucose deprivation, while downregulating dynamin and Fas expression. Further, dynamin inhibition was found to be neuroprotective.

conclusionsDynamin may facilitate Fas-mediated apoptotic death in the brain, and Hsp70 may protect by preventing this trafficking. Dynamin should be explored as a new therapeutic target for neuroprotection.

Indexed as

Down-RegulationAnimalsApoptosisCaspase 8Cell Line, TumorDynaminsfas ReceptorHSP70 Heat-Shock ProteinsHydrazonesInfarction, Middle Cerebral ArteryMiceMice, KnockoutMice, TransgenicNeuronsStrokeCaspase 8DynaminsFas protein, mousefas ReceptorHSP70 Heat-Shock ProteinsHydrazonesN'-(3,4-dihydroxybenzylidene)-3-hydroxy-2-naphthahydrazideapoptosisdynaminFasneuroprotectionstroke

Identifiers

PMID27387989
PMCPMC4961549
OpenAlexW2466477817

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.