Hostname: page-component-8448b6f56d-jr42d Total loading time: 0 Render date: 2024-04-23T14:16:02.544Z Has data issue: false hasContentIssue false
  • English
  • Français

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: logopas@korea.ac.kr
Get access Rights & Permissions [Opens in a new window]

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

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1Kuro-o, M. Klotho and aging. Biochim Biophys Acta 2009;1790:1049–58CrossRefGoogle ScholarPubMed
2Kuro-o, M, Matsumura, Y, Aizawa, H, Kawaguchi, H, Suga, T, Utsugi, T et al. Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 1997;390:45–51CrossRefGoogle ScholarPubMed
3Bartke, A. Long-lived klotho mice: new insights into the roles of IGF-1 and insulin in aging. Trends Endocrinol Metab 2006;17:33–5CrossRefGoogle ScholarPubMed
4Manya, H, Akasaka-Manya, K, Endo, T. Klotho protein deficiency and aging. Geriatr Gerontol Int 2010;10(suppl 1):S80–7CrossRefGoogle ScholarPubMed
5Kurosu, H, Yamamoto, M, Clark, JD, Pastor, JV, Nandi, A, Gurnani, P et al. Suppression of aging in mice by the hormone klotho. Science 2005;309:1829–33CrossRefGoogle ScholarPubMed
6Kamemori, M, Ohyama, Y, Kurabayashi, M, Takahashi, K, Nagai, R, Furuya, N. Expression of klotho protein in the inner ear. Hear Res 2002;171:103–10CrossRefGoogle ScholarPubMed
7Rybak, LP. Mechanisms of cisplatin ototoxicity and progress in otoprotection. Curr Opin Otolaryngol Head Neck Surg 2007;15:364–9CrossRefGoogle ScholarPubMed
8Im, GJ, Chang, JW, Choi, J, Chae, SW, Ko, EJ, Jung, HH. Protective effect of Korean red ginseng extract on cisplatin ototoxicity in HEI-OC1 auditory cells. Phytother Res 2010;24:614–21CrossRefGoogle ScholarPubMed
9Arking, DE, Krebsova, A, Macek M, Sr, Macek, M Jr, Arking, A, Mian, IS et al. Association of human aging with a functional variant of klotho. Proc Natl Acad Sci U S A 2002;99:856–61CrossRefGoogle ScholarPubMed
10Fukino, K, Suzuki, T, Saito, Y, Shindo, T, Amaki, T, Kurabayashi, M et al. Regulation of angiogenesis by the aging suppressor gene klotho. Biochem Biophys Res Commun 2002;293:332–7CrossRefGoogle ScholarPubMed
11Yamamoto, M, Clark, JD, Pastor, JV, Gurnani, P, Nandi, A, Kurosu, H et al. Regulation of oxidative stress by the anti-aging hormone klotho. J Biol Chem 2005;280:38029–34CrossRefGoogle ScholarPubMed
12Kalinec, GM, Webster, P, Lim, DJ, Kalinec, F. A cochlear cell line as an in vitro system for drug ototoxicity screening. Audiol Neurootol 2003;8:177–89CrossRefGoogle Scholar
13Rybak, LP, Whitworth, CA, Mukherjea, D, Ramkumar, V. Mechanisms of cisplatin-induced ototoxicity and prevention. Hear Res 2007;226:157–67CrossRefGoogle ScholarPubMed
14Tatar, M, Bartke, A, Antebi, A. The endocrine regulation of aging by insulin-like signals. Science 2003;299:1346–51CrossRefGoogle ScholarPubMed
15Brunet, A, Bonni, A, Zigmond, MJ, Lin, MZ, Juo, P, Hu, LS et al. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 1999;96:857–68CrossRefGoogle ScholarPubMed
16Wang, Y, Sun, Z. Klotho gene delivery prevents the progression of spontaneous hypertension and renal damage. Hypertension 2009;54:810–17CrossRefGoogle ScholarPubMed
17Xiao, NM, Zhang, YM, Zheng, Q, Gu, J. Klotho is a serum factor related to human aging. Chin Med J (Engl) 2004;117:742–7Google ScholarPubMed