title: Modulation of activator protein 1/DNA binding activity by acoustic overstimulation in the guinea-pig cochlea.
abstract: Changes in gene expression are part of the homeostatic machinery with which cells respond to external stimuli or assaults. The activity of the early response transcriptional factor activator protein-1 (AP-1) can be modulated by a variety of environmental stimuli including those that alter the cellular oxidation/reduction status. This study investigates the activation of AP-1/DNA binding in the guinea-pig cochlea in response to acoustic overstimulation which produces reactive oxygen species. Electrophoretic mobility shift assays revealed that binding of AP-1 to its radiolabeled oligonucleotide probe markedly changed in nuclear extracts of inner ear tissues following intense noise exposure (4 kHz octave band, 115 dB, 5 h). AP-1/DNA binding increased in the organ of Corti and the lateral wall tissues immediately after the exposure, returning to near-baseline levels 5 h later. At 15 h after noise, a second peak of binding activity occurred in the organ of Corti whereas stria vascularis showed a lesser but more sustained activity. Binding in nuclear extracts from the spiral ganglion did not change. Incubation of nuclear extracts with antibodies against Fos/Jun family proteins prior to a supershift assay showed Fra-2 as a major component of the AP-1 complex immediately after the noise exposure. In the organ of Corti, Fra-2 immunoreactivity was localized to the middle turn, i.e. the region which is most affected by the 4-kHz octave band exposure. The results suggest the modulation of gene expression via the activation of AP-1 as a consequence of noise trauma but also demonstrate differential responses in cochlear tissues.
authors.affiliation: Kresge Hearing Research Institute, The University of Michigan, 1301 East Ann Street, Ann Arbor, MI 48109-0506, USA.
authors.forename: T
authors.initials: T
authors.lastname: Matsunobu
authors.forename: K
authors.initials: K
authors.lastname: Ogita
authors.forename: J
authors.initials: J
authors.lastname: Schacht
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods*; D000818:Animals; D003051:Cochlea / Q000033:anatomy & histology / Q000378:metabolism / Q000528:radiation effects*; D004247:DNA / Q000378:metabolism / Q000528:radiation effects*; D004268:DNA-Binding Proteins / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D051921:Fos-Related Antigen-2; D006168:Guinea Pigs; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D009925:Organ of Corti / Q000378:metabolism; D011485:Protein Binding / Q000528:radiation effects; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D051921:Fos-Related Antigen-2; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D004247:DNA