Nuclear factor-kappa B nuclear translocation in the cochlea of mice following acoustic overstimulation.

There is increasing evidence to suggest that the expression of many molecules in the lateral wall of the cochlea plays an important role in noise-induced stress responses. In this study, activation of the nuclear transcription factor nuclear factor-kappa B (NF-kappaB) was investigated in the cochlea of mice treated with intense noise exposure (4 kHz, octave band, 124 dB, for 2 h). The present noise exposure led to remarkable auditory brainstem response threshold shifts and cochlear damage on surface preparations. To assess the effects of noise exposure on NF-kappaB/DNA binding activity in the cochlea, we prepared nuclear extracts from the cochlea at different time points after noise exposure and carried out an electrophoretic mobility shift assay using a probe specific to NF-kappaB. NF-kappaB/DNA binding was significantly enhanced in the cochlea 2-6 h after noise exposure and returned to basal levels after 12 h. Supershift analysis using antibodies against p65 and p50 proteins, which are components of NF-kappaB, demonstrated that enhancement of NF-kappaB/DNA binding was at least in part due to nuclear translocation of p65. An immunohistochemical study also showed that nuclear translocation of both p65 and p50 was observed in the lateral wall after noise exposure and that there may be a possible close association between p65 and enhanced inducible nitric oxide synthase expression. These results suggest that NF-kappaB may have a detrimental role in the response to acoustic overstimulation in the cochlea of mice.