Expression of Cavelin-1 and heme oxygenase-1 in the differentiated vestibular cell line(UB/UE-1) after gentamicin ototoxicity

초록

Objectives : The caveolin is known as a mediator of cell death or survival of injured cell and inhibitor of various signaling pathways, and heme oxygenase as a participant in adaptive and protective responses to oxidative stress like gentamicin-induced vestibular hair cell damage. We examined expressions of caveolin-1 and heme oxygenase-1(HO-1) involved by protein kinase A(PKA) signaling pathway in the differentiated mouse vestibular cell line(UB/UE-1) after gentamicin ototoxicity. Study design : UB/UE-1 cells were cultured at 33’C for 2days and at 39’C for 24hours for differentiation. Cells were treated with 100uM of gentamicin, PKA inhibitor(H89), and aminoguanine(AG) and then incubated for 24hours. Caveolin-1 and HO-1 expressions were examined by western blot. Results : Caveolin-1 was expressed spontaneously in differentiated UB/UE-1 cells and increased after gentamicin treatment. The gentamicin-induced caveolin-1 expression was inhibited by H89 and AG. HO-1 is induced higher in the group of both gentamicin and H89 treatment than gentamicin or H89 alone. Conclusions : Our results indicate that gentamicin-induced caveolin-1 expression is mediated by PKA and NOS signaling pathway, and HO-1 induction can be maximized by inhibition of PKA activity. We conclude that the caveolin-1 and HO-1 expression through a PKA signaling pathway is the important mechanism of gentamicin ototoxicity.