Noise exposure immediately activates cochlear mitogen-activated protein kinase signaling

Abstract

Noise-induced hearing loss (NIHL) is a major public health issue worldwide. Uncovering the early molecular events associated with NIHL would reveal mechanisms leading to the hearing loss. Our aim is to investigate the immediate molecular responses after different levels of noise exposure and identify the common and distinct pathways that mediate NIHL. Previous work showed mice exposed to 116 decibels sound pressure level (dB SPL) broadband noise for 1 h had greater threshold shifts than the mice exposed to 110 dB SPL broadband noise, hence we used these two noise levels in this study. Groups of 4–8-week-old CBA/CaJ mice were exposed to no noise (control) or to broadband noise for 1 h, followed by transcriptome analysis of total cochlear RNA isolated immediately after noise exposure. Previously identified and novel genes were found in all data sets. Following exposure to noise at 116 dB SPL, the earliest responses included up-regulation of 243 genes and down-regulation of 61 genes, while a similar exposure at 110 dB SPL up-regulated 155 genes and down-regulated 221 genes. Bioinformatics analysis indicated that mitogen-activated protein kinase (MAPK) signaling was the major pathway in both levels of noise exposure. Nevertheless, both qualitative and quantitative differences were noticed in some MAPK signaling genes, after exposure to different noise levels. Cacna1b, Cacna1g, and Pla2g6, related to calcium signaling were down-regulated after 110 dB SPL exposure, while the fold increase in the expression of Fos was relatively lower than what was observed after 116 dB SPL exposure. These subtle variations provide insight on the factors that may contribute to the differences in NIHL despite the activation of a common pathway.

Deficit of mitogen-activated protein kinase phosphatase 1 (DUSP1) accelerates progressive hearing loss

“…DUSP1 expression is low during development in almost all tissues except liver and intestine. RNAseq studies indicate that it is expressed in the cochlea and vestibule, particularly in supporting cells (data available from gEAR, umgear.org) (Burns et al, 2015; Elkon et al, 2015; Liu et al, 2014; Scheffer et al, 2015), and that it is upregulated in the cochlea after exposure to noise (Alagramam et al, 2014). In general, MKP family members have been reported to present low basal levels of expression in most tissues (Camps et al, 2000) but they are rapidly induced after stress stimuli.…”

Analysis of serum microRNA expression in male workers with occupational noise-induced hearing loss

“…A comprehensive network and pathway analysis indicated that the MAPK3/MAPK1 MAP kinase serves as one of the crucial nodal molecules in regulating human genetic deafness ( 18 ), highlighting the close association between MAPK signaling pathway and hearing loss. Using a rodent model of noise-induced hearing loss, Alagramam et al ( 19 ) demonstrated that MAPK signaling pathway was activated after noise exposure. MAPK1 , known as ERK2, plays multifactorial roles in mediating cell survival, proliferation, differentiation, and death ( 20 ).…”

Emerging Therapies for Sensorineural Hearing Loss

“…30–34 Specifically, it is hypothesized that cellular stress such as aminoglycoside exposure in the cochlea results in the formation of reactive oxygen species and free radicals that cause the JNK kinase to activate c-Jun. 35 The activated c-Jun transcription factor binds other transcriptional complexes which ultimately results in the complete loss of cochlear hair cells.…”