Mitogen-activated protein kinases (MAP
kinases) are intracellular signaling
kinases activated by phosphorylation in response to a variety of extracellular stimuli. Mammalian MAP
kinase pathways are composed of three major pathways: MEK1 (
mitogen-activated protein kinase kinase 1)/ERK 1/2 (
extracellular signal-regulated kinases 1/2)/
p90 RSK (
p90 ribosomal S6 kinase), JNK (c-Jun amino (
N)-terminal kinase)/c-Jun, and
p38 MAPK pathways. These pathways coordinately mediate physiological processes such as cell survival,
protein synthesis, cell proliferation, growth, migration, and apoptosis. The involvement of MAP
kinase in
noise-induced hearing loss (NIHL) has been implicated in the cochlea; however, it is unknown how expression levels of MAP
kinase change after the onset of NIHL and whether they are regulated by transient phosphorylation or
protein synthesis. CBA/J mice were exposed to 120-dB octave band noise for 2 h. Auditory brainstem response confirmed a component of temporary threshold shift within 0-24 h and significant permanent threshold shift at 14 days after noise exposure. Levels and localizations of phospho- and total- MEK1/ERK1/2/
p90 RSK, JNK/c-Jun, and
p38 MAPK were comprehensively analyzed by the Bio-Plex®
Suspension Array System and immunohistochemistry at 0, 3, 6, 12, 24 and 48 h after noise exposure. The phospho-MEK1/ERK1/2/
p90 RSK signaling pathway was activated in the spiral ligament and the sensory and supporting cells of the organ of Corti, with peaks at 3-6 h and independently of regulations of total-MEK1/ERK1/2/
p90 RSK. The expression of phospho-JNK and
p38 MAPK showed late upregulation in spiral neurons at 48 h, in addition to early upregulations with peaks at 3 h after noise
trauma. Phospho-p38 MAPK activation was dependent on upregulation of total-p38 MAPK. At present, comprehensive data on MAP
kinase expression provide significant insight into understanding the molecular mechanism of NIHL, and for developing therapeutic models for acute
sensorineural hearing loss.