Increased Sensitivity to Noise-Induced Hearing Loss by Blockade of Endogenous PI3K/Akt Signaling

Journal of the Association for Research in Otolaryngology : JARO
Jun ChenSu-Hua Sha

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.

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Citations

Nov 16, 2016·Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology·Yushi HayashiJuichi Ito
Aug 26, 2017·Expert Opinion on Drug Discovery·Daniel Bodmer
Sep 7, 2018·Journal of the Association for Research in Otolaryngology : JARO·Yan YuPezhman Salehi
Apr 17, 2020·International Journal of Molecular Sciences·Janaína C RodriguesRubens de Brito
Oct 12, 2019·The Laryngoscope·Desmond A NunezCathie Garnis
Jul 19, 2020·Gene Therapy·Zhen ZhangFeng Liu
Mar 17, 2021·Cell Biology and Toxicology·Zhiwei ZhengYingzi He
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yi-Chun LinChih-Hung Wang
Jul 3, 2021·International Journal of Molecular Sciences·Maurizio CortadaDaniel Bodmer
Jul 22, 2021·Oxidative Medicine and Cellular Longevity·Yanzhuo ZhangBaoshan Wang
Jul 19, 2021·Environmental Science and Pollution Research International·Long MiaoYuepu Pu

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