Molecular & Cellular Toxicology

The Korean Society of Toxicogenomics and Toxicoproteomics (대한독성유전 단백체학회)
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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)
  • Published : 2009.06.30
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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

References

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