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KMID : 1034820080040030177
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Molecular & Cellular Toxicology
2008 Volume.4 No. 3 p.177 ~ p.182
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An Ototoxic Antibiotic Gentamicin Can Increase PKA-caveolin-1 Signaling Pathway in Differentiated Vestibular Cell Line (UB/UE-1)
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Kim Kyu-Sung
Cho Byung-Han
Choi Ho-Seok
Park Chang-Shin
Jung Yoon-Gun
Kim Young-Mo
Jang Tae-Young
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Abstract
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Caveolin proteins are mediators of cell death or the survival of injured cells, and they are inhibitors of various signaling pathways. The expression of caveolin-, which is involved in the protein kinase A (PKA) signaling pathway, was examined in the differentiated mouse vestibular cell line UB/UE-1 after gentamicin ototoxicity. Caveolae in the vestibular hair cell of healthy guinea pigs were observed through an electron microscope. UB/UE-1 cells were cultured at 95% with 5% at for 48 hours and at 95% with 5% at for 24 hours for differentiation. Cells were treated with 1 mM gentamicin, 0.02 mM H89 (PKA inhibitor), and then incubated for 24 hours. Caveolin-1 expression was examined by western blotting and PKA activity by a assay. Caveolae were observed in the vestibular hair cells of healthy guinea pigs by electron microscopy. Caveolin-1 was expressed spontaneously in differentiated UB/UE-1 cells and increased after gentamicin treatment. PKA was also over-activated by gentamicin treatment. Both gentamicin-induced caveolin-1 expression and PKA over-activation were inhibited by H89. These results indicate that gentamicin-induced caveolin-1 expression is mediated by the PKA signaling pathway. We conclude that caveolae/ caveolin activity, induced via a PKA signaling pathway, may be one of the mechanisms of gentamicin-induced ototoxicity.
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KEYWORD
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Gentamicin, Caveolin, PKA, Vestibular cell, Ototoxicity
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