1. Academic Validation
  2. Anisomycin induces hair cell death and blocks supporting cell proliferation in zebrafish lateral line neuromast

Anisomycin induces hair cell death and blocks supporting cell proliferation in zebrafish lateral line neuromast

  • Comp Biochem Physiol C Toxicol Pharmacol. 2021 Sep;247:109053. doi: 10.1016/j.cbpc.2021.109053.
Xiaoyi Yuan 1 Yanjun Qin 1 Jian Wang 2 Chunxin Fan 3
Affiliations

Affiliations

  • 1 International Research Center for Marine Biosciences, Ministry of Science and Technology, Shanghai Ocean University, China; Institute for Marine Biosystem and Neuroscience, International Center for Marine Studies, Shanghai Ocean University, Shanghai, China.
  • 2 International Research Center for Marine Biosciences, Ministry of Science and Technology, Shanghai Ocean University, China; Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education, Shanghai Ocean University, China.
  • 3 International Research Center for Marine Biosciences, Ministry of Science and Technology, Shanghai Ocean University, China; Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education, Shanghai Ocean University, China; Institute for Marine Biosystem and Neuroscience, International Center for Marine Studies, Shanghai Ocean University, Shanghai, China. Electronic address: [email protected].
Abstract

Ototoxicity of drugs is an important inducement for hearing loss. Anisomycin is a candidate drug for Parasite, Cancer, immunosuppression, and mental disease. However, the ototoxicity of anisomycin has not been examined. In this study, the ototoxicity of anisomycin was evaluated using zebrafish lateral line. We found the zebrafish treated with anisomycin during lateral line development could inhibit hair cell formation in a time- and dose-dependent manner. After neuromasts are mature with differentiated hair cells by 5 day post-fertilization, anisomycin could induce hair cell loss effectively through chronic exposure rather than acute exposure. TUNEL assay and qPCR of Apoptosis related genes tp53, casp8, casp3a, and casp3b indicated that cell apoptotic was induced by chronic anisomycin exposure. Furthermore, knocking down tp53 with antisense morpholino could attenuate the hair cell loss induced by anisomycin. In addition, we found that anisomycin chronic exposure also inhibited the proliferation of supporting cell. Together, these results indicate that chronic anisomycin exposure could induce hair cell death and block supporting cell proliferation, which causes hair cell loss in zebrafish neuromast. This study provides primary ototoxicity evaluation for anisomycin.

Keywords

Anisomycin; Apoptosis; Cell proliferation; Hair cell; Lateral line.

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