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

Nagy, Ivana; Bodmer, Morana; Schmid, Stephan; Bodmer, Daniel

doi:10.1016/j.heares.2005.02.007

Cited by 13 publications

(14 citation statements)

References 26 publications

(32 reference statements)

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“…Additional support comes from our observation that PLZF mRNA levels are increased in the cochlea following stimuli that induce conditioning, including restraint stress, dexamethasone, and acoustic overexposure. Finally, PLZF immunoreactivity is present in the cochlea including the spiral ganglion, the lateral wall, and, as previously noted (Nagy et al, 2005), the organ of Corti, all targets for acoustic trauma (Wang et al, 2002). Our observation that dexamethasone induced similar amounts of protection whether administered before or after the acoustic trauma suggests that the protective effects associated with PLZF are not simply due to attenuating the mechanical stimulus to the organ of Corti, but may involve either attenuation of a damage process that occurs following the stimulus, repair of damage suffered during the acoustic trauma, or both.…”

Section: Discussionsupporting

confidence: 67%

“…Within the organ of Corti (Fig. 3 e ), label was often very strong in the heads and feet of the pillar cells, but was also present in the hair cells and supporting (Deiter's) cells (see also Nagy et al, 2005). To determine whether restraint stress altered PLZF distribution, we exposed mice to restraint stress and immunolabeled the cochlea with antibodies to PLZF.…”

Section: Resultsmentioning

confidence: 96%

“…The cytosolic localization of PLZF both in the control and restrained mice suggests it may be binding and recruiting cytosolic protein targets to the nucleus, as has been demonstrated for its interaction with epsin (Hyman et al, 2000) and with the G-protein coupled angiotensin II receptor (Senbonmatsu et al, 2003). In that regard, PLZF has been shown to be an interaction partner with prestin (Nagy et al, 2005), the major protein functioning as the cochlear amplifier in the outer hair cell (Zheng et al, 2000). Both espin and prestin appear to bind to the same region of PLZF (at the first of nine zinc finger domains near the C terminus), leading Nagy et al (2005) to suggest a similar interaction between PLZF and prestin.…”

Section: Discussionmentioning

confidence: 99%

“…PLZF is a transcription suppressor in the family of Kruppel-type zinc finger proteins and contains a conserved POZ protein-binding domain at its N terminus. PLZF expression is corticosteroid responsive (Fahnenstich et al, 2003; Wasim et al, 2010), is expressed in the inner ear (Nagy et al, 2005), and has been identified as an interaction partner with prestin (Nagy et al, 2005), a cochlear motor protein responsible for amplifying acoustic input to the cochlea (Zheng et al, 2000). Thus PLZF is a reasonable candidate to mediate conditioning-induced protection in the cochlea.…”

Section: Introductionmentioning

confidence: 99%

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A Corticosteroid-Responsive Transcription Factor, Promyelocytic Leukemia Zinc Finger Protein, Mediates Protection of the Cochlea from Acoustic Trauma

Peppi¹,

Kujawa²,

Sewell³

2011

J. Neurosci.

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Animals can be induced to resist cochlear damage associated with acoustic trauma by exposure to a variety of “conditioning” stimuli, including restraint stress, moderate level sound, heat stress, hypoxia, and corticosteroids. Here we identify in mice a corticosteroid-responsive transcription factor, PLZF (promyelocytic leukemia zinc finger protein), which mediates conditioned protection of the cochlea from acoustic trauma. PLZF mRNA levels in the cochlea are increased following conditioning stimuli, including restraint stress, dexamethasone administration, and moderate-to-high level acoustic stimulation. Heterozygous mutant (luxoid.Zbtb16LU/J) mice deficient in PLZF have hearing and responses to acoustic trauma similar to their wild type littermates but are unable to generate conditioning-induced protection from acoustic trauma. PLZF immunoreactivity is present in the spiral ganglion, lateral wall of the cochlea, and organ of Corti, all targets for acoustic trauma. PLZF is also present in the brain and PLZF mRNA in brain is elevated following conditioning stimuli. The identification of a transcription factor that mediates conditioned protection from trauma provides a tool for understanding the protective action of corticosteroids, which are widely used in treating acute hearing loss, and has relevance to understanding the role of corticosteroids in trauma protection.

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Section: Discussionsupporting

confidence: 67%

Section: Resultsmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Corticosteroid-Responsive Transcription Factor, Promyelocytic Leukemia Zinc Finger Protein, Mediates Protection of the Cochlea from Acoustic Trauma

Peppi¹,

Kujawa²,

Sewell³

2011

J. Neurosci.

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“…Five-day-old SD rats were anesthetized and perfusions were performed as described previously (Nagy et al 2005). Following deparaffinization, inner ear tissue slices were washed once in PBS and incubated in 0.5% Triton-X (Sigma) in 0.15% BSA/PBS and normal goat serum for 2 h. Incubation with the primary antibody directed against RelA (p65) was performed overnight at 4-C.…”

Section: Immunohistochemistrymentioning

confidence: 99%

NF-κB is Required for Survival of Immature Auditory Hair Cells In Vitro

Nagy

Monge

Albinger-Hegyi

et al. 2005

JARO

Self Cite

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Damage to auditory hair cells in the inner ear as a consequence of aging, disease, acoustic trauma, or exposure to ototoxins underlies most cases of hearing impairment. Because the mammalian ear cannot replace damaged hair cells, loss of hearing is irreversible and progressive throughout life. One of the current goals of inner ear biology is to develop therapeutic strategies to prevent hair cell degeneration. Although important progress has been made in discovering factors that mediate hair cell death, very little is known about the molecular pathway(s) that signal survival. Here we considered the role of NF-kB, a ubiquitous transcription factor that plays a major role in the regulation of many apoptosis-and stressrelated genes, in mediating hair cell survival. NF-kB was detected in a constitutively active form in the organ of Corti of 5-day-old rats. Selective inhibition of NF-kB through use of a cell-permeable inhibitory peptide in vitro caused massive degeneration of hair cells within 24 h of inhibitor application. Hair cell death occurred through an apoptotic pathway through activation of caspase-3 and may involve transcriptional down-regulation of the gadd45b gene, an anti-apoptotic NF-kB target. In view of our results, it seems likely that NF-kB may participate in normal hair cell function.Keywords: apoptosis, inhibitor of kB, inner ear, organ of Corti, RelAAbbreviations: a -antibody; bp -base pair; BSAbovine serum albumin; CHAPS -3-[(3-Cholamidopropyl)dimethylammonio]-1-propanesulfonate; DMSO -dimethyl sulfoxide; DTT -dithiothreitol; EDTA -ethylendiaminetetraacetic acid; EGTA -ethylenglycol-bis(b-aminoethyl)-N,N,N 0 ,N 0 -tetraacetic acid; FITC -fluorescein isothiocyanate; GADD45b -growth arrest and DNA damage-inducible 45b protein; GAPDH -glyceraldehydes-3-phosphate dehydrogenase protein; HEPES -N-2-Hydroxyethylpiperazine-N 0 -2-ethanesulfonic acid; IB -immunoblotting; IHC -inner hair cell; IkB -inhibitor of kB protein; INH -Synthetic inhibitor of NF-kB protein; INHMut -synthetic inactive control for the inhibitor of NF-kB protein; JNK -c-Jun N-terminal kinase; MIPmultiple image processing; NF-kB -nuclear factor-kB; NT -not treated; OC -organ of Corti; OHC -outer hair cell; p5 -postnatal day 5; PBS -phosphate-buffered saline; PMSF -phenylYmethyl-sulfonyl fluoride; PNT -parthenolide; Rel -reticuloendotheliosis viral oncogene homologue; RT -reverse transcriptase; SG -spiral ganglion; SV -stria vascularis; XIAP -Xlinked inhibitor of apoptosis protein.

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Prestin–prestin and prestin–GLUT5 interactions in HEK293T cells

Currall

Yamashita

et al. 2007

Developmental Neurobiology

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The remarkable hearing sensitivity and frequency selectivity in mammals is attributed to cochlear amplifier in the outer hair cells (OHCs). Prestin, a membrane protein in the lateral wall of OHC plasma membrane, is required for OHC electromotility and cochlear amplifier. In addition, GLUT5, a fructose transporter, is reported to be abundant in the plasma membrane of the OHC lateral wall and has been originally proposed as the OHC motor protein. Here we provide evidence of interactions between prestin/prestin and prestin/GLUT5 in transiently transfected HEK293T cells. We used a combination of techniques: (1) membrane colocalization by confocal microscopy, (2) fluorescence resonance energy transfer (FRET) by fluorescence activated cell sorting (FACS), (3) FRET by acceptor photobleaching, (4) FRET by fluorescence lifetime imaging (FRET-FLIM), and (5) coimmunoprecipitation. Our results suggest that homomeric and heteromeric prestin interactions occur in native OHCs to facilitate its electromotile function and that GLUT5 interacts with prestin for its elusive function.

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

Cited by 13 publications

References 26 publications

A Corticosteroid-Responsive Transcription Factor, Promyelocytic Leukemia Zinc Finger Protein, Mediates Protection of the Cochlea from Acoustic Trauma

A Corticosteroid-Responsive Transcription Factor, Promyelocytic Leukemia Zinc Finger Protein, Mediates Protection of the Cochlea from Acoustic Trauma

NF-κB is Required for Survival of Immature Auditory Hair Cells In Vitro

Prestin–prestin and prestin–GLUT5 interactions in HEK293T cells

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