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Cell Biology International (2010) 34, 1219–1225 (Printed in Great Britain)
Involvement of calpain-I and microRNA34 in kanamycin-induced apoptosis of inner ear cells
Li Yu*†‡, Hao Tang*1, Xiao Hua Jiang†1, Lai Ling Tsang†, Yiu Wa Chung† and Hsiao Chang Chan†
*Department of Physiology, China Medical University Shen Yang, Liao Ning 110000, Peoples Republic of China, †Epithelial Cell Biology Research Center, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, NT, Hong Kong, and ‡Department of Physiology, Liao Ning Medical University, Jin Zhou, Liao Ning 121001, Peoples Republic of China

Inner ear cells, including hair cells, spiral ganglion cells, stria vascularis cells and supporting cells on the basilar membrane, play a major role in transducing hearing signals and regulating inner ear homoeostasis. However, their functions are often damaged by antibiotic-induced ototoxicity. Apoptosis is probably involved in inner ear cell injury following aminoglycoside treatment. Calpain, a calcium-dependent protease, is essential for mediating and promoting cell death. We have therefore investigated the involvement of calpain in the molecular mechanism underlying ototoxicity induced by the antibiotic kanamycin in mice. Kanamycin (750 mg/kg) mainly induced cell death of cochlear cells, including stria vascularis cells, supporting cells and spiral ganglion cells, but not hair cells within the organ of Corti. Cell death due to apoptosis occurred in a time-dependent manner with concomitant up-regulation of calpain expression. Furthermore, the expression levels of two microRNAs, mir34a and mir34c, were altered in a dose-dependent manner in cochlear cells. These novel findings demonstrated the involvement of both calpain and microRNAs in antibiotic-induced ototoxicity.

Key words: apoptosis, calpain, kanamycin, microRNA, ototoxicity

Abbreviations: ABR, auditory brainstem response, miRNAs, microRNAs, PI, propidium iodide, qRT-PCR, quantitative RT-PCR

1To whom correspondence should be addressed (email or

Part of a series marking the 70th birthday of the Cell Biology International Editor-in-Chief Denys Wheatley

Received 12 July 2010; accepted 9 September 2010

Published online 2 November 2010, doi:10.1042/CBI20100515

© The Author(s) Journal compilation © 2010 Portland Press Limited

ISSN Print: 1065-6995
ISSN Electronic: 1095-8355
Published by Portland Press Limited on behalf of the International Federation for Cell Biology (IFCB)