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

Area of Science:

• Oto-neuroscience
• Cellular and Molecular Biology
• Auditory Physiology

Background:

• Acoustic overstimulation induces cochlear hair cell death via apoptosis.
• The mitochondrial signaling pathway, involving Bcl-2 family proteins, mediates this cell death.
• Myeloid cell leukemia sequence 1 (Mcl-1), an antiapoptotic protein, has an uncharacterized role in noise-induced hair cell death.

Purpose of the Study:

• To investigate the endogenous and noise-induced expression of Mcl-1 in Sprague Dawley rat cochleae.
• To determine Mcl-1's involvement in the pathogenesis of noise-induced hair cell death.

Main Methods:

• Analysis of Mcl-1 mRNA and protein expression in normal and noise-exposed rat cochleae.
• Western blot analysis to confirm the form of Mcl-1.
• Immunolabeling to localize Mcl-1 protein in hair cells.

Main Results:

• Strong constitutive Mcl-1 mRNA expression in normal cochlear sensory epithelia, with preferential protein expression in outer hair cells.
• Noise exposure (115 dB SPL for 1 hr) led to time-dependent Mcl-1 mRNA up-regulation at 4 hr and protein up-regulation at 1 day postexposure.
• Increased Mcl-1 immunoreactivity was observed in the nuclear region of apoptotic and surviving hair cells post-noise exposure.

Conclusions:

• Mcl-1 is constitutively expressed in the cochlea and its expression is altered by acoustic stress.
• Mcl-1 is implicated in the regulation of hair cell apoptosis following acoustic overstimulation.
• Mcl-1 may influence nuclear events in apoptosis, contributing to hair cell survival or death under acoustic stress.