Dataset Information

Acoustic overstimulation modifies Mcl-1 expression in cochlear sensory epithelial cells.

ABSTRACT: Acoustic overstimulation causes apoptotic cell death in the cochlea. This death process is mediated, in part, by the mitochondrial signaling pathway involving Bcl-2 family proteins. Myeloid cell leukemia sequence 1 (Mcl-l) is an antiapoptotic member of the Bcl-2 family. Its involvement in noise-induced hair cell death has not been characterized. Here we report the endogenous expression and the noise-induced expression of Mcl-1 in Sprague Dawley rat cochleae. In the sensory epithelia of normal cochleae, there is strong constitutive expression of Mcl-1 mRNA, with an expression level higher than that of many other Bcl-2 family genes. The Mcl-1 protein is preferentially expressed in outer hair cells. After exposure to a high level of continuous noise at 115-dB sound pressure level for 1 hr, Mcl-1 expression displays a time-dependent alteration, with up-regulation of Mcl-1 mRNA at 4 hr postexposure and protein up-regulation at 1 day postexposure. Western blot analysis reveals the up-regulated Mcl-1 as the full-length form of Mcl-1. Immunolabeling of the Mcl-1 protein reveals the early increase in Mcl-1 immunoreactivity in the nuclear region of the hair cells displaying apoptotic phenotypes and a subsequent increase in survival hair cells. These results suggest that Mcl-1 is involved in the regulation of hair cell pathogenesis resulting from acoustic stress, possibly by influencing the nuclear events of apoptosis.

SUBMITTER: Hu BH

PROVIDER: S-EPMC3521497 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Acoustic overstimulation modifies Mcl-1 expression in cochlear sensory epithelial cells.

Hu Bo Hua BH Cai Qunfeng Q

Journal of neuroscience research 20100601 8

Acoustic overstimulation causes apoptotic cell death in the cochlea. This death process is mediated, in part, by the mitochondrial signaling pathway involving Bcl-2 family proteins. Myeloid cell leukemia sequence 1 (Mcl-l) is an antiapoptotic member of the Bcl-2 family. Its involvement in noise-induced hair cell death has not been characterized. Here we report the endogenous expression and the noise-induced expression of Mcl-1 in Sprague Dawley rat cochleae. In the sensory epithelia of normal co ...[more]

PMID: 20091770

Similar Datasets

Project description:Electromotile activity in auditory outer hair cells (OHCs) is essential for sound amplification. It relies on the highly specialized membrane motor protein prestin, and its interactions with the cytoskeleton. It is believed that the expression of prestin and related molecules involved in OHC electromotility may be dynamically regulated by signals from the acoustic environment. However little is known about the nature of such signals and how they affect the expression of molecules involved in electromotility in OHCs. We show evidence that prestin oligomerization is regulated, both at short and relatively long term, by acoustic input and descending efferent activity originating in the cortex, likely acting in concert. Unilateral removal of the middle ear ossicular chain reduces levels of trimeric prestin, particularly in the cochlea from the side of the lesion, whereas monomeric and dimeric forms are maintained or even increased in particular in the contralateral side, as shown in Western blots. Unilateral removal of the auditory cortex (AC), which likely causes an imbalance in descending efferent activity on the cochlea, also reduces levels of trimeric and tetrameric forms of prestin in the side ipsilateral to the lesion, whereas in the contralateral side prestin remains unaffected, or even increased in the case of trimeric and tetrameric forms. As far as efferent inputs are concerned, unilateral ablation of the AC up-regulates the expression of α10 nicotinic Ach receptor (nAChR) transcripts in the cochlea, as shown by RT-Quantitative real-time PCR (qPCR). This suggests that homeostatic synaptic scaling mechanisms may be involved in dynamically regulating OHC electromotility by medial olivocochlear efferents. Limited, unbalanced efferent activity after unilateral AC removal, also affects prestin and β-actin mRNA levels. These findings support that the concerted action of acoustic and efferent inputs to the cochlea is needed to regulate the expression of major molecules involved in OHC electromotility, both at the transcriptional and posttranscriptional levels.

Dataset Information

Acoustic overstimulation modifies Mcl-1 expression in cochlear sensory epithelial cells.

Publications

Acoustic overstimulation modifies Mcl-1 expression in cochlear sensory epithelial cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets