The Role of Caveolin is It New Molecular Target for Modulation of Aging Process in Cochlear Hair Cells ?

초록

According to the gate theory, certain biomolecules such as caveolins, amphiphysins, G proteins, and integrins play decisive roles in determining the senescent phenotype and thus provide targets for modulating the aging process. Among these molecules, caveolin can associate with a varity of regulatory and structural molecules via their scaffolding domains and thereby influence a broad spectrum of biological phenomena including both the physiology and morphology of the senescent cells. If caveolin may be a component on the deterministic nature on aging, we think that also in cochlear hair cells it become molecular target for modulation of aging process. First we investigated the basal expression of caveolin-1, caveolin-2, caveolin-3, NOS and SOD in UB/OC-1 cells(cochlear hair cells). and then with the use of RNA interference technique, we wanted to know whether downregulation of caveolin influence telomerase activity and reactive oxygen species (ROS) production in cochlear hair cells. The result was that there was presence of caveolin-1 chiefly in UB/OC-1 hair cells and down-regulation of Caveolin-1 reduced protein kinase a (PKA) activity. Telemerase was activated by caveolin down-regulation and caveolin down-regulation inhibits oxidative stress in mitochondrial level. in conclusion, down-regulation of caveolin-1 reduces oxidative stress in mitochondrial level. and down-regulation of caveolin-1 induces decrease of PKA activity. Telemerase activity is increased by downregulating caveolin-1 or by PKA inhibitor, thus caveolin-1 may have anti-aging effect in cochlear cells with or without relation to PKA.