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The Role of Caveolin-1 in Senescence and Ototoxicity of Differentiated Cochlear Hair Cell Line (UB/OC-1)  

Jung, Yoon-Gun (Department of Otolaryngology-Head and Neck Surgery, College of Medicine Inha University)
Kim, Kyu-Sung (Department of Otolaryngology-Head and Neck Surgery, College of Medicine Inha University)
Hwang, In-Kug (Department of Otolaryngology-Head and Neck Surgery, College of Medicine Inha University)
Jang, Tae-Young (Department of Otolaryngology-Head and Neck Surgery, College of Medicine Inha University)
Kim, Young-Mo (Department of Otolaryngology-Head and Neck Surgery, College of Medicine Inha University)
Choi, Ho-Seok (Department of Otolaryngology-Head and Neck Surgery, College of Medicine Inha University)
Publication Information
Molecular & Cellular Toxicology / v.5, no.2, 2009 , pp. 133-140 More about this Journal
Abstract
Caveolin may be a molecular target for modulation of aging process in cochlear hair cells and have association with oxotoxicity. First we investigated the basal expression of caveolin-1, caveolin-2, caveolin-3, nitric oxide synthase, and superoxide dismutase in UB/OC-1 cochlear hair cell line. By using a RNA interference technique, we investigated whether down-regulation of caveolin influenced telomerase activity and reactive oxygen species (ROS) production in cochlear hair cells. In addition, cisplatin and gentamycin, known ototoxic drugs, were administered to the cochlear cells to determine their impact on caveolin expression. Further attempts at elucidating cellular aging mechanism with caveolin and ototoxic drugs were carried out. The main discoveries were the presence of caveolin-1 in UB/OC-1 cells and that down-regulation of caveolin-1 reduced protein kinase A activity. Telomerase was activated by caveolin down-regulation and caveolin down-regulation inhibited oxidative stress at the mitochondrial level. When cisplatin and gentamycin were administered to the cochlear hair cells during a caveolin expression state, a decrease in telomerase activity and increase ROS activity was observed. Caveolin-1 may modulate the senescent mechanisms in cochlear cells. An increase in caveolin-1 levels can lead to ROS production in the mitochondria which may cause ototoxicity.
Keywords
Caveolin; Gentamycin; Ototoxicity; Protein Kinase A;
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1 Park, S. C. New molecular target for modulation of aging process. Antioxidant & Redox Signaling 8:620-627 (2005)   DOI   ScienceOn
2 Engelman, J. A. et al. Molecular genetics of the caveolin gene family: implications for human cancers, diabetes, Alzheimer disease, and muscular dystrophy. Am J Hum Genet 63:1578-1587 (1998)   DOI   ScienceOn
3 Tuper, G., Ahmad, N. & Seidman, M. Mechanism of ototoxicity. Perspectives on Hearing and Hearing Disorders: Research and Diagnostic 9:2-10 (2005)
4 Brockenbrough, J. M., Rybak, L. P. & Matz, G. J. Oto-toxicity. In B. J. Bailey (Ed.), Head and neck surgeryotolaryngology Philadelphia: Lippincott, pp. 1893-1898 (2001)
5 Evans, P. & Halliwell, B. Free radicals and hearing: Cause, consequence, and criteria. Annals of the New York Academy of Sciences 884:19-40 (1999)   DOI   PUBMED
6 Blasco, M. A. Telomere length, stem cells and aging. Nature Chemical Biology 10:640-649 (2007)   DOI   ScienceOn
7 Racine, C. & Couet, J. Reduction of caveolin 1 gene expression in lung carcinoma cell lines. Biochem Biophyl Res Commun 255:580-586 (1999)   DOI   ScienceOn
8 Priuska, E. M. & Schacht, J. Formation of free radicals by gentamicin and iron and evidence for an iron/gentamicin complex. Biochem Pharmacol 50:1749-1752 (1995)   DOI   ScienceOn
9 Schaefer, S. D., Wright, C. G., Post, J. D. & Frenkel, E. P. Cisplatinum vestibular toxicity. Cancer 47:857-859 (1981)   DOI   ScienceOn
10 Gratton, M. A. & Smyth, B. J. Ototoxicity of platinum compounds. In P. S. Roland & J. A. Rutka (Eds.), Hamilton, Ontario, Canada: B. C. Decker. Ototoxicity. pp. 60-75 (2004)
11 Takumida, M. & Anniko, M. Nitric oxide in guinea pig vestibular sensory cells following gentamicin exposure in vitro. Acta Otolaryngol 121:346-350 (2001)   DOI   ScienceOn
12 Park, W. Y. et al. Up-regulation of caveolin attenuates epidermal growth factor sigaling in senescent cells. J Bio Chem 275:20847-20852 (2000)   DOI   ScienceOn
13 Dehne, N., Rauen, U., de Groot, H. & Lautermann, J. Involvement of the mitochondrial permeability transition in gentamicin ototoxicity. Hearing Research 169:47-55 (2002)   DOI   ScienceOn
14 Takumida, M. & Anniko, M. Detection of nitric oxide in the guinea pig inner ear, using a combination of aldehyde fixative and 4,5-diaminofluorescein diacetate. Acta Otolaryngol 141:460-464 (2001)   DOI   ScienceOn
15 Cai, C. & Chen, J. Overexpression of caveolin-1 induces alteration of multidrug resistance in Hs578T breast adenocarcinoma cells. Int J Cancer 111:522-529 (2004)   DOI   ScienceOn
16 Segal, J. A. & Skolnick, P. Polyamine-like actions of aminoglycosides and aminoglycoside derivatives at NMDA receptors. Eur J Pharmacol 347:311-317 (1998)   DOI   PUBMED   ScienceOn
17 Trushina, E., Charme, J. D., Parisi, J. & McMurray, C. T. Neurological abnormalities in caveolin-1 knock out mice. Behavioural Brain Research 172:24-32 (2006)   DOI   ScienceOn
18 Takumida, M. & Anniko, M. Nitric oxide in the inner ear. Curr Opin Neurol 15:11-15 (2002)   DOI   ScienceOn
19 Frank, P. G. & Lisanti, M. P. Caveolin-1 and caveolae in atherosclerosis: differential roles in fatty streak formation and neointimal hyperplasia. Curr Opin Lipidol 15:523-529 (2004)   DOI   ScienceOn
20 Razani, B., Woodman, S. E. & Lisanti, M. P. Caveolae: from cell biology to animal physiology. Pharmacol Rev 5:431-467 (2002)