Involvement of calpain-I and microRNA34 in kanamycin-induced apoptosis of inner ear cells.
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.
Department of Physiology, China Medical University Shen Yang, Liao Ning 110000, Peoples Republic of China.
Li
L
Yu
Hao
H
Tang
Xiao Hua
XH
Jiang
Lai Ling
LL
Tsang
Yiu Wa
YW
Chung
Hsiao Chang
HC
Chan
D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D002154:Calpain / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002477:Cells / Q000187:drug effects / Q000378:metabolism; D007758:Ear, Inner / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects; D020287:In Situ Nick-End Labeling; D007612:Kanamycin / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects
D000900:Anti-Bacterial Agents; C551848:MIRN34a microRNA, mouse; D035683:MicroRNAs; D007612:Kanamycin; D002154:Calpain