Functional Mechanotransduction Is Required for Cisplatin-Induced Hair Cell Death in the Zebrafish Lateral Line

Andrew J Thomas; Dale W Hailey; Tamara M Stawicki; Patricia Wu; Allison B Coffin; Edwin W Rubel; David W Raible; Julian A Simon; Henry C Ou

doi:10.1523/JNEUROSCI.3940-12.2013

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Functional Mechanotransduction Is Required for Cisplatin-Induced Hair Cell Death in the Zebrafish Lateral Line

Journal article

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Functional Mechanotransduction Is Required for Cisplatin-Induced Hair Cell Death in the Zebrafish Lateral Line

Andrew J Thomas, Dale W Hailey, Tamara M Stawicki, Patricia Wu, Allison B Coffin, Edwin W Rubel, David W Raible, Julian A Simon and Henry C Ou

The Journal of neuroscience, Vol.33(10), pp.4405-4414

03/06/2013

DOI: https://doi.org/10.1523/JNEUROSCI.3940-12.2013

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https://hdl.handle.net/2376/103999

PMCID: PMC3666553

PMID: 23467357

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https://doi.org/10.1523/JNEUROSCI.3940-12.2013View

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Abstract

Cisplatin, one of the most commonly used anticancer drugs, is known to cause inner ear hair cell damage and hearing loss. Despite much investigation into mechanisms of cisplatin-induced hair cell death, little is known about the mechanism whereby cisplatin is selectively toxic to hair cells. Using hair cells of the zebrafish lateral line, we found that chemical inhibition of mechanotransduction with quinine and EGTA protected against cisplatin-induced hair cell death. Furthermore, we found that the zebrafish mutants mariner ( myo7aa ) and sputnik ( cad23 ) that lack functional mechanotransduction were resistant to cisplatin-induced hair cell death. Using a fluorescent analog of cisplatin, we found that chemical or genetic inhibition of mechanotransduction prevented its uptake. These findings demonstrate that cisplatin-induced hair cell death is dependent on functional mechanotransduction in the zebrafish lateral line.

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Title: Functional Mechanotransduction Is Required for Cisplatin-Induced Hair Cell Death in the Zebrafish Lateral Line
Creators: Andrew J Thomas - Virginia Merrill Bloedel Hearing Research Center
Dale W Hailey - Virginia Merrill Bloedel Hearing Research Center
Tamara M Stawicki - Virginia Merrill Bloedel Hearing Research Center
Patricia Wu - Virginia Merrill Bloedel Hearing Research Center
Allison B Coffin - Virginia Merrill Bloedel Hearing Research Center
Edwin W Rubel - Virginia Merrill Bloedel Hearing Research Center
David W Raible - Virginia Merrill Bloedel Hearing Research Center
Julian A Simon - Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, and
Henry C Ou - Virginia Merrill Bloedel Hearing Research Center
Publication Details: The Journal of neuroscience, Vol.33(10), pp.4405-4414
Academic Unit: Integrative Physiology and Neuroscience, Department of
Publisher: Society for Neuroscience
Identifiers: 99900546812801842
Language: English
Resource Type: Journal article