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Updated: Jun 12, 2026
Dissection of Adult Mouse Utricle and Adenovirus-mediated Supporting-cell Infection
Published on: March 28, 2012
Corticotropin-releasing factor-2 activation prevents gentamicin-induced oxidative stress in cells derived from the
Johnvesly Basappa1, Sevin Turcan, Douglas E Vetter
1Department of Neuroscience, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
Abstract:
Generation of reactive oxygen species (ROS) is a common denominator in many conditions leading to cell death in the cochlea, yet little is known of the cochlea's endogenous mechanisms involved in preventing oxidative stress and its consequences in the cochlea. We have recently described a corticotropin-releasing factor (CRF) signaling system in the inner ear involved in susceptibility to noise-induced hearing loss. We use biochemical and proteomics assays to define further the role of CRF signaling in the response of cochlear cells to aminoglycoside exposure. We demonstrate that activity via the CRF(2) class of receptors protects against aminoglycoside-induced ROS production and activation of cell death pathways. This study suggests for the first time a role for CRF signaling in protecting the cochlea against oxidative stress, and our proteomics data suggest novel mechanisms beyond induction of free radical scavengers that are involved in its protective mechanisms.
Insights
Corticotropin-releasing factor (CRF) signaling via CRF(2) receptors protects cochlear cells from oxidative stress and cell death caused by aminoglycosides. This reveals a novel protective mechanism against hearing loss.
Area of Science:
- Oto-neurology
- Cellular biology
- Molecular mechanisms of hearing loss
Background:
- Reactive oxygen species (ROS) contribute to cochlear cell death.
- Endogenous mechanisms protecting the cochlea from oxidative stress are poorly understood.
- A corticotropin-releasing factor (CRF) signaling system in the inner ear influences noise-induced hearing loss.
Purpose of the Study:
- To investigate the role of CRF signaling in cochlear cell response to aminoglycoside exposure.
- To define the protective mechanisms of CRF signaling against aminoglycoside-induced ototoxicity.
Main Methods:
- Biochemical assays
- Proteomics analysis
- Assessment of ROS production
- Evaluation of cell death pathways
Main Results:
- CRF signaling, specifically through CRF(2) receptors, protects against aminoglycoside-induced ROS production.
- CRF(2) receptor activity inhibits aminoglycoside-induced activation of cell death pathways.
- Proteomics data suggest novel protective mechanisms beyond free radical scavengers.
Conclusions:
- CRF signaling plays a protective role in the cochlea against oxidative stress.
- CRF(2) receptor activation is a key component in mitigating aminoglycoside ototoxicity.
- This study uncovers new molecular pathways involved in cochlear protection from oxidative damage.
