Molecular Mechanism of Tinnitus from the Standpoint of Autophagy

Abstract

Objectives: Recent studies described that the expression of BDNF was decreasing in patients with depression and severe tinnitus. However, the relationship between the incidence of tinnitus and the role of BDNF still remain unclear in auditory cells. The aim of this study is to consider the molecular mechanism of tinnitus from the standpoint of the autophagy-based regulation of cell death and BDNF signaling pathway in auditory cells. Methods: We used auditory cell line HEI-OC1 in this study. Tunicamycin was used as endoplasmic reticulum (ER) stress. The viability of HEI-OC1 was determined by cell viability assays. Immunofluorescent confocal laser microscopy was used. Western blot was performed. Results: It was confirmed that autophagy was consistently induced in HEI-OC1 after treatment of tunicamycin. The cell viability after treatment of tunicamycin was decreased in dose- and time-dependent matter. The expression of BDNF which has the potential to become a biomarker of tinnitus and calcium-dependent activator protein for secretion 2 (CAPS2), which promotes BDNF section, were decreased in tunicamycin treated HEI-OC1 cells. The expression of Bcl-2 which controls apoptosis and Beclin1 that regulates autophagy were decreased in tunicamycin treated HEI-OC1 cells. Conclusions: We consider that Bcl-2 and Beclin 1 serve as adapter proteins between BDNF signaling pathway and autophagy in auditory cells under ER stress. Our results led to the suggestion that the autophagy-mediated regulation of cell death and BDNF signaling pathway play a major part of the incidence of tinnitus.