Functional mechanotransduction is required for Cisplatin-induced hair cell death in the zebrafish lateral line
- Authors
- Thomas, A.J., Hailey, D.W., Stawicki, T.M., Wu, P., Coffin, A.B., Rubel, E.W., Raible, D.W., Simon, J.A., and Ou, H.C.
- ID
- ZDB-PUB-130329-6
- Date
- 2013
- Source
- The Journal of neuroscience : the official journal of the Society for Neuroscience 33(10): 4405-4414 (Journal)
- Registered Authors
- Raible, David, Stawicki, Tamara
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Antineoplastic Agents/pharmacology*
- Calcium/metabolism
- Cell Count/methods
- Cell Death/drug effects
- Cell Death/genetics
- Cisplatin/pharmacology*
- Egtazic Acid/pharmacology
- Embryo, Nonmammalian
- Female
- Fluorescent Dyes
- Green Fluorescent Proteins/genetics
- Hair Cells, Auditory/drug effects*
- Hair Cells, Auditory/metabolism
- Larva
- Lateral Line System/cytology*
- Lateral Line System/drug effects
- Male
- Mechanoreceptors/drug effects*
- Microscopy, Fluorescence
- Myosins/metabolism
- Quinine/pharmacology
- Zebrafish
- Zebrafish Proteins/genetics
- PubMed
- 23467357 Full text @ J. Neurosci.
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.