Glucocorticoid receptor and nuclear factor-kappa B interactions in restraint stress-mediated protection against acoustic trauma.
The role of glucocorticoid receptors (GRs) in the protective effect of restraint stress (RS) before acoustic trauma was studied in spiral ganglion neurons of CBA mice. RS increased corticosterone and protected against elevated auditory brain stem thresholds caused by acoustic trauma. This protection was inhibited by the pretreatment with a corticosterone synthesis inhibitor, metyrapone (MET), and a GR antagonist (RU486). RS followed by acoustic trauma caused an immediate increase in corticosterone that triggered nuclear translocation of GR, without a change in the expression of GR protein. RU486 + MET before RS and acoustic trauma caused an immediate increase in GR mRNA followed by increased GR protein expression (24 h after trauma). GR signaling was further characterized by analyzing nuclear factor-kappaB (NF kappaB) nuclear translocation and protein expression. NF kappaB nuclear translocation was reduced after acoustic trauma or pretreatment with RU486 + MET before RS and acoustic trauma. On the contrary, RS protected against the trauma-induced NF kappaB reduction of its nuclear translocation in inhibitory-kappaB (I kappaB)-dependent manner. RU486 + MET caused a simultaneous decreased I kappaB expression and NF kappaB nuclear translocation, demonstrating an interference with the I kappaB-mediated activation of NF kappaB. In summary, RS protects the cochlea from acoustic trauma by increasing corticosterone and activating GRs. These results emphasis how GR activity modulates hearing sensitivity and its importance for the rationale use of glucocorticoids in inner ear diseases.
Tahera
Yeasmin
Y
Department of Physiology and Pharmacology, Karolinska Institutet, 171 77 Stockholm, Sweden.
Meltser
Inna
I
Johansson
Peter
P
Hansson
Anita C
AC
Canlon
Barbara
B
D000818:Animals; D001692:Biological Transport; D002467:Cell Nucleus / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D006317:Hearing Loss, Noise-Induced / Q000517:prevention & control*; D020672:I-kappa B Proteins / Q000494:pharmacology; D008297:Male; D008797:Metyrapone / Q000494:pharmacology; D051379:Mice; D008808:Mice, Inbred CBA; D015735:Mifepristone / Q000494:pharmacology; D016328:NF-kappa B / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000502:physiology*; D012149:Restraint, Physical; D015398:Signal Transduction; D013136:Spiral Ganglion / Q000378:metabolism; D013312:Stress, Physiological / Q000503:physiopathology*
D020672:I-kappa B Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D003345:Corticosterone; D008797:Metyrapone