Time Courses of Changes in Phospho- and Total- MAP Kinases in the Cochlea after Intense Noise Exposure

Yukihide Maeda, Kunihiro Fukushima, Ryotaro Omichi, Shin Kariya, Kazunori Nishizaki

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere58775
JournalPLoS One
Volume8
Issue number3
DOIs
Publication statusPublished - Mar 6 2013

Fingerprint

90-kDa Ribosomal Protein S6 Kinases
Cochlea
p38 Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinases
mitogen-activated protein kinase
Noise
Audition
Noise-Induced Hearing Loss
Phosphotransferases
Acoustic noise
Phosphorylation
Up-Regulation
JNK Mitogen-Activated Protein Kinases
Spiral Ligament of Cochlea
MAP Kinase Kinase 1
Physiological Phenomena
hearing
Organ of Corti
phosphotransferases (kinases)
Inbred CBA Mouse

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Time Courses of Changes in Phospho- and Total- MAP Kinases in the Cochlea after Intense Noise Exposure. / Maeda, Yukihide; Fukushima, Kunihiro; Omichi, Ryotaro; Kariya, Shin; Nishizaki, Kazunori.

In: PLoS One, Vol. 8, No. 3, e58775, 06.03.2013.

Research output: Contribution to journalArticle

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