Akt and c-Jun N-terminal kinase are regulated in response to moderate noise exposure in the cochlea of guinea pigs.
The molecular mechanisms induced in the inner ear after noise exposure are not well understood. Akt and c-Jun N-terminal kinase (JNK) are key factors of signaling pathways balancing cellular survival and apoptosis. Therefore, we analyzed the spatial distribution of Akt, JNK, their respective activated (i.e. phosphorylated) forms, p-Akt and p-JNK, as well as NF kappa B by immunohistochemistry after 70- and 90-dB noise exposure in an animal model. Alterations of the expression patterns compared to unexposed animals were quantified by a computer-based image analysis method. In unexposed specimens, Akt, p-Akt, JNK, p-JNK were found to be commonly expressed in different regions of the cochlea, whereas NF kappa B was exclusively restricted to the lateral wall. After noise stimulation, the expression of the different molecules was downregulated with the exception of JNK. JNK remained largely unchanged or increased JNK levels were identified in ganglion cells and Schwann cells after 70 dB as well as in the unstained nerve fibers. The stable or increasing levels of JNK might be indicative of a preapoptotic state. The downregulation of Akt in the cochlea might support these activities. p-Akt was not reduced in the spiral ganglion cells after 90-dB exposure and was upregulated in the unstained nerve fibers, probably indicating a counteracting prosurvival cellular reaction in these tissues. In conclusion, we suggest that the observed alterations in both the Akt and JNK pathways are part of a noise distress-induced response indicating pro- and antiapoptotic activities in the different tissues of the cochlea.
Selivanova
Oxana
O
Department of Otorhinolaryngology, Mainz Medical School, Mainz, Germany.
Brieger
Jürgen
J
Heinrich
Ulf-Rüdiger
UR
Mann
Wolf
W
D000818:Animals; D017209:Apoptosis; D003051:Cochlea / Q000378:metabolism* / Q000473:pathology; D006168:Guinea Pigs; D007090:Image Interpretation, Computer-Assisted; D007150:Immunohistochemistry; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009412:Nerve Fibers / Q000378:metabolism; D009622:Noise / Q000009:adverse effects*; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D009925:Organ of Corti / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D015398:Signal Transduction; D013136:Spiral Ganglion / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D016328:NF-kappa B; D042461:Vascular Endothelial Growth Factor A; D051058:Oncogene Protein v-akt; D048031:JNK Mitogen-Activated Protein Kinases