title: Functional mechanotransduction is required for cisplatin-induced hair cell death in the zebrafish lateral line.
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.
authors: Virginia Merrill Bloedel Hearing Research Center, Department of Otolaryngology-Head and Neck Surgery, University of Washington, Seattle, Washington 98195, USA.
authors: Andrew J
authors: AJ
authors: Thomas
authors: Dale W
authors: DW
authors: Hailey
authors: Tamara M
authors: TM
authors: Stawicki
authors: Patricia
authors: P
authors: Wu
authors: Allison B
authors: AB
authors: Coffin
authors: Edwin W
authors: EW
authors: Rubel
authors: David W
authors: DW
authors: Raible
authors: Julian A
authors: JA
authors: Simon
authors: Henry C
authors: HC
authors: Ou
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology*; D004533:Egtazic Acid / Q000494:pharmacology; D004625:Embryo, Nonmammalian; D005260:Female; D005456:Fluorescent Dyes; D049452:Green Fluorescent Proteins / Q000235:genetics; D006198:Hair Cells, Auditory / Q000187:drug effects* / Q000378:metabolism; D007814:Larva; D053403:Lateral Line System / Q000166:cytology* / Q000187:drug effects; D008297:Male; D008465:Mechanoreceptors / Q000187:drug effects*; D008856:Microscopy, Fluorescence; D000081412:Myosin VIIa; D009218:Myosins / Q000378:metabolism; D011803:Quinine / Q000494:pharmacology; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D005456:Fluorescent Dyes; D000081412:Myosin VIIa; D029961:Zebrafish Proteins; D049452:Green Fluorescent Proteins; D004533:Egtazic Acid; D011803:Quinine; D009218:Myosins; D002945:Cisplatin; D002118:Calcium