FKBP51 protects hair cells of utricles from gentamicin-induced toxicity in vitro: possible relation to the activities of NF-κB signaling pathway

Abstract

FK506-binding protein 51 (FKBP51) belongs to the immunophilin family, which is related to regulation of cell growth and apoptosis. The present study was designed to explore the expression of FKBP51 in murine utricle hair cells (HCs) and the possible mechanisms underpinning the actions of FKBP51 relevant to gentamicin-mediated toxicity, with special attention given to nuclear factor-kappa B (NF-κB) activities in vitro. Here, we found, for the first time, that FKBP51 was widely expressed in both cytoplasm and cytomembrane. Moreover, the expression of FKBP51 in cultured HCs of utricle was downregulated after exposure to 1 mM gentamicin for 24 h. Then, the fkbp51 knockout mice were utilized to further investigate the role of FKBP51 in HCs in response to gentamicin. And the absence of FKBP51 led to severe HCs loss, accumulated ROS levels, and increased apoptotic factors, which could be alleviated by 2 mM N-acetyl-l-cysteine (NAC) to certain degree. In addition, mechanistic studies with 10 mM BAY 11–7082 showed that FKBP51 protected HCs against gentamicin-induced damage, at least in part, via blocking the NF-κB pathway activation. Taken together, our new findings suggest that FKBP51 might serve as a new target for the prevention of HCs of utricle from aminoglycoside-induced vestibular toxicity.