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Citations to this article

Fluorescent aminoglycosides reveal intracellular trafficking routes in mechanosensory hair cells
Dale W. Hailey, … , Edwin W. Rubel, David W. Raible
Dale W. Hailey, … , Edwin W. Rubel, David W. Raible
Published December 19, 2016
Citation Information: J Clin Invest. 2017;127(2):472-486. https://doi.org/10.1172/JCI85052.
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Research Article Cell biology Article has an altmetric score of 14

Fluorescent aminoglycosides reveal intracellular trafficking routes in mechanosensory hair cells

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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.

Authors

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

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 Total
Citations: 1 7 3 5 8 9 3 5 7 48
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2017 (7)

Title and authors Publication Year
Aminoglycoside-Induced Cochleotoxicity: A Review
M Jiang, T Karasawa, PS Steyger
Frontiers in cellular neuroscience 2017
Towards the Prevention of Aminoglycoside-Related Hearing Loss
ME OSullivan, A Perez, R Lin, A Sajjadi, AJ Ricci, AG Cheng
Frontiers in cellular neuroscience 2017
Potential Mechanisms Underlying Inflammation-Enhanced Aminoglycoside-Induced Cochleotoxicity
M Jiang, F Taghizadeh, PS Steyger
Frontiers in cellular neuroscience 2017
PI3K and Inhibitor of Apoptosis Proteins Modulate Gentamicin- Induced Hair Cell Death in the Zebrafish Lateral Line
H Wiedenhoft, L Hayashi, AB Coffin
Frontiers in cellular neuroscience 2017
SS-31 peptide enables mitochondrial targeting drug delivery: a promising therapeutic alteration to prevent hair cell damage from aminoglycosides
X Kuang, S Zhou, W Guo, Z Wang, Y Sun, H Liu
Drug Delivery 2017
Use antibiotics in cell culture with caution: genome-wide identification of antibiotic-induced changes in gene expression and regulation
AH Ryu, WL Eckalbar, A Kreimer, N Yosef, N Ahituv
Scientific Reports 2017
Apoptosis in inner ear sensory hair cells
S Morrill, DZ He
Journal of Otology 2017

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