Noise overstimulation induces immediate early genes in the rat cochlea.
In mammals, exposure to intense noise produces a permanent hearing loss called permanent threshold shift (PTS), whereas a moderate noise produces only a temporary threshold shift (TTS). Little is known about the molecular responses to such high intensity noise exposures. In this study we used gene arrays to examine the early response to acoustic overstimulation in the rat cochlea. We compared cochlear RNA from noise-exposed rats with RNA from unexposed controls. The intense PTS noise induced several immediate early genes encoding both transcription factors (c-FOS, EGR1, NUR77/TR3) and cytokines (PC3/BTG2, LIF and IP10). In contrast, the TTS noise down-regulated the gene for growth hormone. The response of these genes to different noise intensities was examined by quantitative RT-PCR 2.5 h after the 90-min noise exposure. For most genes, the extent of induction correlates with the intensity of the noise exposure. Three proteins (EGR1, NUR77/TR3, and IP10) were detected in many regions of the unexposed cochlea. After exposure to 120 dB noise, these proteins were present at higher levels or showed extended expression in additional regions of the cochlea. LIF was undetectable in the cochlea of unexposed rats, but could be seen in the organ of Corti and spiral ganglion neurons following noise. NUR77/TR3 was a nuclear protein before noise, but following noise translocated to the cytoplasm. These studies provide new insights into the molecular response to noise overstimulation in the mammalian cochlea.
Cho
Younsook
Y
Department of Cell and Developmental Biology, The University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Gong
Tzy-Wen L
TW
Kanicki
Ariane
A
Altschuler
Richard A
RA
Lomax
Margaret I
MI
D000161:Acoustic Stimulation; D000818:Animals; D001345:Autoradiography / Q000379:methods; D003051:Cochlea / Q000033:anatomy & histology / Q000528:radiation effects*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D015870:Gene Expression / Q000528:radiation effects*; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000528:radiation effects; D017781:Genes, Immediate-Early / Q000502:physiology*; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008297:Male; D009622:Noise; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D015221:Potassium Channels / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear; D053606:Receptors, OSM-LIF; D011987:Receptors, Steroid; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C104577:IP10-Mig receptor; D017874:Immediate-Early Proteins; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; C507842:Lifr protein, rat; C539820:Nr4a1 protein, rat; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D018160:Receptors, Cytoplasmic and Nuclear; D053606:Receptors, OSM-LIF; D011987:Receptors, Steroid; D014157:Transcription Factors