Evidence map›Paper›PMID 27991862›Full record

ArticleThe Journal of clinical investigation2017

Fluorescent aminoglycosides reveal intracellular trafficking routes in mechanosensory hair cells.

Dale W Hailey, Robert Esterberg, Tor H Linbo, Edwin W Rubel, David W Raible

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed
4.9field-weighted citation impact, top 5% 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

53 citing papers in PubMed, 81 citations in OpenAlex.

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  11. Frontiers in pharmacology · 2024
    Article
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  18. Identifying targets to prevent aminoglycoside ototoxicity.Molecular and cellular neurosciences · 2022
    Review
  19. Article
  20. AnFrontiers in molecular neuroscience · 2022
    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 3 institutions in 2 countries.

Dale W Hailey
Robert Esterberg
Tor H Linbo
Edwin W Rubel
David W Raible
Merrill (United States) · USInstitute for Stem Cell Biology and Regenerative Medicine · INUniversity of Washington · US

Funding

Genetics of Zebrafish Hair Cell ToxicityR01DC005987 · NIDCD · UNIVERSITY OF WASHINGTON · PI RAIBLE, DAVID W · 2003 to 2023
$9.8M
Intelligent Imaging Spinning Disk Confocal MicroscopeS10RR026826 · NCRR · UNIVERSITY OF WASHINGTON · PI RAIBLE, DAVID W · 2010 to 2010
$500k
Intercellular trafficking of labeled aminoglycosides in living hair cellsR03DC012881 · NIDCD · UNIVERSITY OF WASHINGTON · PI HAILEY, DALE WARREN · 2012 to 2014
$456k
NCRR NIH HHS S10 RR026826NIDCD NIH HHS R01 DC005987NIDCD NIH HHS R03 DC012881
6 · The paper itself

Abstract

Aminoglycosides (AGs) are broad-spectrum antibiotics that are associated with kidney damage, balance disorders, and permanent hearing loss. This damage occurs primarily by killing of proximal tubule kidney cells and mechanosensory hair cells, though the mechanisms underlying cell death are not clear. Imaging molecules of interest in living cells can elucidate how molecules enter cells, traverse intracellular compartments, and interact with sites of activity. Here, we have imaged fluorescently labeled AGs in live zebrafish mechanosensory hair cells. We determined that AGs enter hair cells via both nonendocytic and endocytic pathways. Both routes deliver AGs from the extracellular space to lysosomes, and structural differences between AGs alter the efficiency of this delivery. AGs with slower delivery to lysosomes were immediately toxic to hair cells, and impeding lysosome delivery increased AG-induced death. Therefore, pro-death cascades induced at early time points of AG exposure do not appear to derive from the lysosome. Our findings help clarify how AGs induce hair cell death and reveal properties that predict toxicity. Establishing signatures for AG toxicity may enable more efficient evaluation of AG treatment paradigms and structural modifications to reduce hair cell damage. Further, this work demonstrates how following fluorescently labeled drugs at high resolution in living cells can reveal important details about how drugs of interest behave.

Indexed as

AminoglycosidesFluorescent DyesAnimalsBiological Transport, ActiveCell DeathHair Cells, VestibularZebrafishAminoglycosidesFluorescent Dyes

Identifiers

PMID27991862
PMCPMC5272180
OpenAlexW2565597953

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.