Related Experiment Video

Updated: Jun 5, 2025

Dissection of Adult Mouse Utricle and Adenovirus-mediated Supporting-cell Infection
11:13

Dissection of Adult Mouse Utricle and Adenovirus-mediated Supporting-cell Infection

Published on: March 28, 2012

23.7K

ARC protects cochlear hair cells from neomycin-induced ototoxicity via the Ras/JNK signaling pathway

Xiaoyu Yu1, Hanbing Gao2, Jie Zhang3

  • 1Department of Otolaryngology, Hangzhou First People's Hospital, School of Medicine, Affiliated to Westlake University, Hangzhou, Zhejiang, China; The Fourth school of Medicine Affiliated to Zhejiang Chinese Medical University, Hangzhou, China.

Toxicology Letters
|December 12, 2024
PubMed

Insights

Apoptosis repressor with caspase recruitment domain (ARC) protects hair cells from neomycin damage by reducing apoptosis via the Ras/JNK pathway. This offers new strategies for preventing drug-induced ototoxicity and cochlear hair cell death.

Area of Science:

  • Ototoxicity research
  • Cellular and molecular biology
  • Signaling pathways

Background:

  • Neomycin is a common ototoxic drug causing hair cell damage.
  • Apoptosis repressor with caspase recruitment domain (ARC) is a key protein in cell survival.
  • Understanding ARC's role in hair cell protection is crucial for treating hearing loss.

Purpose of the Study:

  • To investigate the protective role and mechanism of ARC against neomycin-induced hair cell damage.
  • To explore the involvement of the Ras/JNK signaling pathway in ARC-mediated protection.
  • To provide insights into preventing drug-induced ototoxicity.

Main Methods:

  • Utilized HEI-OC1 cells and basilar membrane cultures for experiments.
  • Employed plasmid transfection to modulate ARC and Ras expression.
  • Assessed cell viability, apoptosis, cleaved caspase-3, p-CREB, and p-c-Jun levels.

Main Results:

  • ARC overexpression enhanced HEI-OC1 cell viability and reduced apoptosis post-neomycin treatment.
  • Cleaved caspase-3 levels decreased, while p-CREB increased and p-c-Jun decreased in ARC-overexpressing cells.
  • Ras and JNK inhibition reduced ARC expression; Ras overexpression increased ARC expression.

Conclusions:

  • ARC protects hair cells from neomycin-induced apoptosis through the Ras/JNK signaling pathway.
  • ARC acts as a protective factor against neomycin-induced ototoxicity.
  • Findings suggest potential therapeutic strategies targeting ARC for cochlear hair cell preservation.
Keywords:
ARCHair cellsMAPKsNeomycinOtotoxicityRas

More Related Videos

Trans-Tympanic Drug Delivery for the Treatment of Ototoxicity09:52

Trans-Tympanic Drug Delivery for the Treatment of Ototoxicity

Published on: March 16, 2018

9.3K
Cochlear Implant Surgery and Electrically-evoked Auditory Brainstem Response Recordings in C57BL/6 Mice09:06

Cochlear Implant Surgery and Electrically-evoked Auditory Brainstem Response Recordings in C57BL/6 Mice

Published on: January 9, 2019

13.8K

Related Concept Videos

Hair Cells01:22

Hair Cells

Hair cells are the sensory receptors of the auditory system—they transduce mechanical sound waves into electrical energy that the nervous system can understand. Hair cells are located in the organ of Corti within the cochlea of the inner ear, between the basilar and tectorial membranes. The actual sensory receptors are called inner hair cells. The outer hair cells serve other functions, such as sound amplification in the cochlea, and are not discussed in detail here.
40.0K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.2K
The Cochlea01:13

The Cochlea

The cochlea is a coiled structure in the inner ear that contains hair cells—the sensory receptors of the auditory system. Sound waves are transmitted to the cochlea by small bones attached to the eardrum called the ossicles, which vibrate the oval window that leads to the inner ear. This causes fluid in the chambers of the cochlea to move, vibrating the basilar membrane.
44.5K