Related Experiment Video
Updated: Aug 6, 2025
Dissection of Adult Mouse Utricle and Adenovirus-mediated Supporting-cell Infection
Published on: March 28, 2012
TIGAR Protects Cochlear Hair Cells against Teicoplanin-Induced Damage
Qiongmin Zhang1,2, Zhiqun Yao1,2, Fang Chen1,2
1Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong University, Jinan, Shandong, China.
Abstract:
Teicoplanin is a glycopeptide antibiotic used to treat severe staphylococcal infections. It has been claimed that teicoplanin possesses ototoxic potential, although its toxic effects on cochlear hair cells (HCs) remain unknown. The TP53-induced glycolysis and apoptosis regulator (TIGAR) plays a crucial role in promoting cell survival. Prior research has demonstrated that TIGAR protects spiral ganglion neurons against cisplatin damage. However, the significance of TIGAR in damage to mammalian HCs has not yet been investigated. In this study, firstly, we discovered that teicoplanin caused dose-dependent cell death in vitro in both HEI-OC1 cells and cochlear HCs. Next, we discovered that HCs and HEI-OC1 cells treated with teicoplanin exhibited a dramatically decrease in TIGAR expression. To investigate the involvement of TIGAR in inner ear injury caused by teicoplanin, the expression of TIGAR was either upregulated via recombinant adenovirus or downregulated by shRNA in HEI-OC1 cells. Overexpression of TIGAR increased cell viability, decreased apoptosis, and decreased intracellular reactive oxygen species (ROS) level, whereas downregulation of TIGAR decreased cell viability, exacerbated apoptosis, and elevated ROS level following teicoplanin injury. Finally, antioxidant therapy with N-acetyl-L-cysteine decreased ROS level, prevented cell death, and restored p38/phosphorylation-p38 expression levels in HEI-OC1 cells injured by teicoplanin. This study demonstrates that TIGAR may be a promising novel target for the prevention of teicoplanin-induced ototoxicity.
Insights
Teicoplanin causes cochlear hair cell death by reducing TIGAR expression. Upregulating TP53-induced glycolysis and apoptosis regulator (TIGAR) protects against this damage, suggesting TIGAR as a target for preventing teicoplanin ototoxicity.
Area of Science:
- Ototoxicity research
- Cellular and molecular biology
- Pharmacology
Background:
- Teicoplanin, an antibiotic for severe staphylococcal infections, is suspected of ototoxicity.
- The role of TP53-induced glycolysis and apoptosis regulator (TIGAR) in protecting cochlear hair cells from damage is unknown.
- TIGAR is known to protect neurons from cisplatin damage.
Purpose of the Study:
- To investigate the effects of teicoplanin on cochlear hair cells (HCs).
- To determine the role of TIGAR in teicoplanin-induced ototoxicity.
- To explore TIGAR as a potential therapeutic target for preventing hearing loss.
Main Methods:
- In vitro study using HEI-OC1 cells and primary cochlear HCs.
- Teicoplanin treatment to induce cell death and assess TIGAR expression.
- TIGAR expression manipulated using recombinant adenovirus (upregulation) and shRNA (downregulation).
- Assessment of cell viability, apoptosis, and reactive oxygen species (ROS) levels.
- Antioxidant therapy with N-acetyl-L-cysteine.
Main Results:
- Teicoplanin induced dose-dependent cell death in HCs and HEI-OC1 cells.
- Teicoplanin treatment significantly decreased TIGAR expression.
- TIGAR overexpression enhanced cell viability, reduced apoptosis, and lowered ROS levels.
- TIGAR downregulation decreased cell viability, increased apoptosis, and elevated ROS levels.
- N-acetyl-L-cysteine treatment reduced ROS, prevented cell death, and restored p38 signaling.
Conclusions:
- Teicoplanin-induced ototoxicity involves a decrease in TIGAR expression.
- TIGAR plays a protective role against teicoplanin-induced damage to cochlear HCs.
- TIGAR represents a potential novel therapeutic target for mitigating teicoplanin-induced hearing loss.
Related Concept Videos
01:22Hair Cells
00:50Unrenewable Cells
Photoreceptors
The retina is composed of several layers and contains specialized cells called photoreceptors. The photoreceptors (rods and cones) change their membrane potential when stimulated by light energy. There are two types of photoreceptors—rods and cones—which differ in the shape of...