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Sensory epithelial cells in the organ of Corti survive throughout life.However, factors for sensory epithelial cell survival are poorly understood at the present time.Here we demonstrated that brain-derived neurotrophic factor (BDNF),a factor committing to neuronal survival, regulates the survival of sensory epithelial cells (OC1) through phosphatidylinositide 3-OH kinase (PI3K)/protein kinase B (Akt) and/or nuclear factor kappa B (NF-κB)/B cell lymphoma 2 (Bcl-2) pathways.BDNF activated PI3K/Akt kinases and activated or increased NF-κB/Bcl-2 activity or expression in association with the survival of 0C1 cells in vitro.LY294002, a specific inhibitor for PI3K, and pyrrolidine dithiocarbamate (PDTC), an inhibitor for NF-κB, abrogated the protective effect of BDNF on OC1 cells, causing the increased expression of caspase 3 and the apoptotic cell numbers in vitro.Similarly, a dominant negative mutant of I kappa B alpha (IκBαM, a specific inhibitor of NE-Κb) abrogated the protective effect of BDNFon OC1 cells.The data demonstrate that BDNF increases the survival of sensory epithelial cells through the PI3K/Akt and NF-Κb/Bcl-2 signaling pathways.