Downregulation of P66Shc Can Reduce Oxidative Stress and Apoptosis in Oxidative Stress Model of Marginal Cells of Stria Vascularis in Sprague Dawley Rats

Overview

Journal Drug Des Devel Ther

Specialty Pharmacology

Date 2019 Nov 6

PMID 31686782

Citations 10

Authors

Cong Hao

Xuewen Wu

Ruoyu Zhou

Hao Zhang

Yulai Zhou

Xinxing Wang

Yong Feng

Lingyun Mei

Chufeng He

Xinzhang Cai

Lisha Wu

Affiliations

Soon will be listed here.

Abstract

Background: p66Shc, a Src homologue and collagen homologue (Shc) adaptor protein, mediates oxidative stress signaling. The p66Shc-null mice have increased lifespan and enhanced resistance to oxidative stress. Studies have also indicated its potential role in inner ear aging, which can lead to deafness.

Objective: The aim of this study was to determine the effects of p66Shc down-regulation on the marginal cells (MCs) of the inner ear stria vascularis.

Methods: Primary MCs were isolated from neonatal rats and treated with glucose oxidase to induce oxidative stress. The cells were transduced with adenovirus expressing siRNA, and the knockdown was verified by Western blotting. The reactive oxygen species (ROS) levels and apoptosis were analyzed using the DCFH-DA probe and Annexin-V/7-AAD staining respectively. The ultrastructure of the differentially-treated cells was examined by transmission electron microscopy (TEM). The in vitro oxidative stress model was established successfully in rat MCs. Knockdown of p66Shc alleviated the high ROS levels and apoptosis in the glucose oxidase-treated cells. In addition, glucose oxidase significantly increased the number of peroxisomes in the MCs, which was decreased by p66Shc inhibition.

Conclusion: Oxidative stress increases p66Shc levels in the marginal cells of the inner ear, which aggravates ROS production and cellular injury. Blocking p66Shc expression can effectively reduce oxidative stress and protect the MCs.

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