Promyelocytic leukemia zinc finger protein localizes to the cochlear outer hair cells and interacts with prestin, the outer hair cell motor protein.

Hair cells in the auditory sensory organ are specialized mechanoreceptors common to mammalian and non-mammalian species. The mammalian cochlear outer hair cells (OHC) possess a distinct motile property, dubbed membrane-based electromotility, that enhances the receptor function. This electromotility is believed to be the basis of cochlear amplification that increases sensitivity of the mammalian ear to sound.

Early gene expression in the organ of Corti exposed to gentamicin.

Studies have demonstrated different pathogenetic key factors in gentamicin-induced hair cell death. The production of reactive oxygen species (ROS), as well as apoptosis-related genes, play a critical role. However, a coordinated large-scale investigation of gene expression in the organ of Corti (OC) exposed to gentamicin has not yet been conducted.

Fas ligand expression in the organ of Corti.

We have previously demonstrated by FACS analysis and histochemistry that Fas ligand (FasL) increases on cochlear cell surfaces after immune response or stimulation with gamma-interferon (IFN-gamma). To determine whether the appearance of FasL on cochlear cell membranes is related to gene expression or to posttranslational events, cochlear cells were treated with IFN-gamma. They were evaluated for FasL gene expression by real-time PCR and for FasL protein localization by confocal microscopy of permeabilized and immunolabeled cells.

Gentamicin-induced hair cell death is not dependent on the apoptosis receptor Fas.

Objectives/hypothesis: The hair cells are the most vulnerable elements in the cochlea, and damage to them is the most common cause of sensorineural hearing loss. Understanding the intracellular events that lead to the death of hair cells is a key to developing protective strategies. The Fas death receptor-mediated apoptotic pathway is well studied and plays an important role in the elimination of damaged cells in a number of different cellular systems.

The Drosophila Hox gene deformed sculpts head morphology via direct regulation of the apoptosis activator reaper.

Hox proteins control morphological diversity along the anterior-posterior body axis of animals, but the cellular processes they directly regulate are poorly understood. We show that during early Drosophila development, the Hox protein Deformed (Dfd) maintains the boundary between the maxillary and mandibular head lobes by activating localized apoptosis. Dfd accomplishes this by directly activating the cell death promoting gene reaper (rpr).