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Protective effect of klotho protein against cisplatin ototoxicity in an auditory cell line

Published online by Cambridge University Press:  15 August 2012

Se Jin Park ,
So Hyun Park ,
Ji Won Chang ,
June Choi ,
Hak Hyun Jung  and
Gi Jung Im
Se Jin Park
Affiliation:
Department of Otolaryngology–Head and Neck Surgery, College of Medicine, Seoul, South Korea
So Hyun Park
Affiliation:
Department of Biomedical Sciences, Korea University, Seoul, South Korea
Ji Won Chang
Affiliation:
Department of Otolaryngology–Head and Neck Surgery, College of Medicine, Seoul, South Korea
June Choi
Affiliation:
Department of Otolaryngology–Head and Neck Surgery, College of Medicine, Seoul, South Korea
Hak Hyun Jung
Affiliation:
Department of Otolaryngology–Head and Neck Surgery, College of Medicine, Seoul, South Korea Department of Biomedical Sciences, Korea University, Seoul, South Korea
Gi Jung Im*
Affiliation:
Department of Otolaryngology–Head and Neck Surgery, College of Medicine, Seoul, South Korea
*
Address for correspondence: Dr Gi Jung Im, Department of Otolaryngology–Head and Neck Surgery, Korea University College of Medicine, 126-1 Anamdong 5-ga, Seongbuk-ku, Seoul, 136–705, South Korea Fax: (82) 2 925 5233 E-mail: [email protected]
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Abstract

Objectives:

Klotho protein is involved in insulin-signalling and ageing. Klotho mutation causes premature ageing and significantly shortens the lifespan. The anti-neoplastic drug cisplatin promotes ototoxicity at higher doses by inducing apoptosis. This study aimed to clarify the effect of klotho expression on cisplatin ototoxicity, using an auditory cell line.

Materials and methods:

Expressions of klotho messenger RNA and protein were analysed by reverse-transcription polymerase chain reaction and western blotting. Auditory cells (HEI-OC1 line) were pretreated with 2 nM klotho protein for 2 hours; 15 µM cisplatin was then applied. After 48 hours incubation, assessment of cell viability (via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay), apoptosis (via Hoechst 33258 staining) and reactive oxygen species was performed.

Results:

Klotho protein expression increased in cisplatin-treated auditory cells. Cells treated with both klotho protein and cisplatin showed a viability of 67.7 per cent, versus 59.4 per cent in cisplatin-treated cells. Klotho significantly attenuated the cisplatin-induced increase in reactive oxygen species, and increased the viability of cells with cisplatin-induced cytotoxicity.

Conclusion:

Klotho protein is protective against cisplatin-induced auditory cell cytotoxicity; inhibition of reactive oxygen species may be the main mechanism.

Keywords

Klotho ProteinMouseCisplatinAuditory Hair CellReactive Oxygen Species
Type
Main Articles
Information
The Journal of Laryngology & Otology , Volume 126 , Issue 10 , October 2012 , pp. 1003 - 1009
Copyright
Copyright © JLO (1984) Limited 2012

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