Corticotropin-releasing factor-2 activation prevents gentamicin-induced oxidative stress in cells derived from the inner ear.
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.
Basappa
Johnvesly
J
Department of Neuroscience, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
Turcan
Sevin
S
Vetter
Douglas E
DE
D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death; D002461:Cell Line, Transformed; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D007758:Ear, Inner / Q000166:cytology; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D005839:Gentamicins / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*; D011500:Protein Synthesis Inhibitors / Q000633:toxicity*; D020543:Proteome / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism
D005839:Gentamicins; D011500:Protein Synthesis Inhibitors; D020543:Proteome; D017382:Reactive Oxygen Species; D003346:Corticotropin-Releasing Hormone; D013482:Superoxide Dismutase; D053148:Caspase 3