title: Increased Sensitivity to Noise-Induced Hearing Loss by Blockade of Endogenous PI3K/Akt Signaling.
abstract: The PI3K/Akt signaling pathway is involved in mediating survival of sensory hair cells. Here, we investigated the involvement of PI3K/Akt in noise-induced hearing loss in both temporary and permanent threshold shift noise models. The PI3K regulatory subunit p85α and phosphorylation of Akt on serine 473 (p-Akt S473) are downregulated in sensory hair cells, including both outer and inner hair cells, and supporting cells of the mouse organ of Corti 1 h after exposure to permanent-threshold-shift-inducing noise (PTS noise), but not with temporary-threshold-shift-inducing noise (TTS noise). In contrast, the PI3K catalytic subunit p110α and phosphorylation of Akt on threonine 308 (p-Akt T308) do not change with PTS or TTS noise. Additionally, mice pretreated with p85α small interfering RNA (siRNA) have decreased expression of p-Akt1 (S473) in their sensory hair cells and increased sensitivity to TTS noise-induced hearing loss. Finally, Akt1-knockout mice also have enhanced sensitivity to TTS noise-induced hearing loss. In conclusion, this study suggests that endogenous PI3K/Akt signaling is an intrinsic protective mechanism of the inner ear. Blockade of PI3K/Akt signaling pathways increases sensitivity to TTS noise-induced hearing loss.
authors: Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Walton Research Building, Room 403-E, 39 Sabin Street, Charleston, SC, 29425, USA, edondongcccj@aliyun.com.
authors: Jun
authors: J
authors: Chen
authors: Hu
authors: H
authors: Yuan
authors: Andra E
authors: AE
authors: Talaska
authors: Kayla
authors: K
authors: Hill
authors: Su-Hua
authors: SH
authors: Sha
mesh_terms: D000818:Animals; D001309:Auditory Threshold; D006317:Hearing Loss, Noise-Induced / Q000209:etiology*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt