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

Nagy, Ivana; Monge, Arianne; Albinger-Hegyi, Andrea; Schmid, Stephan; Bodmer, Daniel

doi:10.1007/s10162-005-0006-7

Cited by 41 publications

(43 citation statements)

References 35 publications

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“…Similar to these reports we found a constitutively active form of NF-kappaB in the organ of Corti (OC) of 5-day-old rats. Selective inhibition of NFkappaB in vitro caused massive degeneration of HCs within 24 h of inhibitor application [Nagy et al, 2005]. These data suggest an important role for NF-kappaB in mediating survival of immature auditory HCs.…”

mentioning

confidence: 60%

“…We have previously shown that this compound and concentration causes HC loss [Nagy et al, 2005]. In the control experiments, an inactive control for the NF-kappaB inhibitor was used (NF-kappaB control, AAVALLPAVLLALLAPVQRDG-QKLMP, Santa Cruz Biotechnology Inc.) at the same final concentration.…”

Section: Inhibition Of Nf-kappab Activitymentioning

confidence: 99%

“…Recently, we could demonstrate that NF-kappaB, a transcription factor that plays a major role in the regulation of many apoptosis-and stress-related genes, is required for the survival of immature auditory HCs in vitro [Nagy et al, 2005]. In most cells, NF-kappaB is kept inactive in the cytoplasm through interaction with I-kappaB.…”

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confidence: 99%

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NF-kappaB-Dependent Apoptotic Hair Cell Death in the Auditory System

et al. 2007

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Hair cells are the most vulnerable elements in the inner ear and their degeneration is the most common cause of hearing loss. In the last few years progress has been made in uncovering the molecular mechanisms involved in hair cell damage and death. However, little is known about factors important for hair cell survival. Recently, it has been demonstrated that the transcription factor NF-kappaB is required for survival of immature auditory hair cells in vitro. Here we used DNA microarray technology to explore NF-kappaB downstream events in organ of Corti explants of postnatal day-5 Sprague-Dawley rats which were exposed to a cell-permeable NF-kappaB-inhibitory peptide. Gene expression was analyzed using DNA microarray technology. Genes were selected on the basis of comparative analysis, which reliably distinguished the NF-kappaB inhibitor-treated samples from control samples. Interestingly, among the up-regulated genes was the gene coding for the regulatory subunit of phosphatidylinositol 3-kinase. Moreover, inhibition of the phosphatidylinositol 3-kinase signaling pathway in organ of Corti explants exposed to the NF-kappaB inhibitor reduced caspase-3 activation. These data link NF-kappaB-dependent hair cell death to phosphatidylinositol 3-kinase signaling.

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confidence: 60%

Section: Inhibition Of Nf-kappab Activitymentioning

confidence: 99%

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NF-kappaB-Dependent Apoptotic Hair Cell Death in the Auditory System

et al. 2007

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“…In rat cochlear explants, treatment with an Akt inhibitor promotes gentamicininduced outer hair cell (OHC) death (Chung et al 2006) and diminishes the protective function of dexamethasone against TNFα-initiated apoptosis (Haake et al 2009). Moreover, inhibition of the downstream Akt target NF-κB by aminoglycosides leads to loss of sensory hair cells in explants (Nagy et al 2005(Nagy et al , 2007 and mouse cochleae (Jiang et al 2006). Taken together, this evidence suggests that increasing PI3K/Akt signaling might protect the inner ear from noxious stimuli.…”

Section: Introductionmentioning

confidence: 80%

Increased Sensitivity to Noise-Induced Hearing Loss by Blockade of Endogenous PI3K/Akt Signaling

Chen

Talaska

et al. 2015

JARO

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The PI3K/Akt signaling pathway is involved in mediating survival of sensory hair cells. Here, we investigated the involvement of PI3K/Akt in noise-induced hearing loss in both temporary and permanent threshold shift noise models. The PI3K regulatory subunit p85α and phosphorylation of Akt on serine 473 (p-Akt S473) are downregulated in sensory hair cells, including both outer and inner hair cells, and supporting cells of the mouse organ of Corti 1 h after exposure to permanent-threshold-shift-inducing noise (PTS noise), but not with temporary-threshold-shiftinducing noise (TTS noise). In contrast, the PI3K catalytic subunit p110α and phosphorylation of Akt on threonine 308 (p-Akt T308) do not change with PTS or TTS noise. Additionally, mice pretreated with p85α small interfering RNA (siRNA) have decreased expression of p-Akt1 (S473) in their sensory hair cells and increased sensitivity to TTS noise-induced hearing loss. Finally, Akt1-knockout mice also have enhanced sensitivity to TTS noise-induced hearing loss. In conclusion, this study suggests that endogenous PI3K/Akt signaling is an intrinsic protective mechanism of the inner ear. Blockade of PI3K/Akt signaling pathways increases sensitivity to TTS noise-induced hearing loss.

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“…in vitro (Nagy et al, 2005). However, there is little information regarding activation of NFB in the auditory nerve and how NFB activity may affect cochlear function with age and trauma.…”

Section: Discussionmentioning

confidence: 99%

Nuclear Factor κB Deficiency Is Associated with Auditory Nerve Degeneration and Increased Noise-Induced Hearing Loss

Lang¹,

Schulte²,

Zhou³

et al. 2006

J. Neurosci.

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Degeneration of the spiral ganglion neurons (SGNs) of the auditory nerve occurs with age and in response to acoustic injury. Histopathological observations suggest that the neural degeneration often begins with an excitotoxic process affecting the afferent dendrites under the inner hair cells (IHCs), however, little is known about the sequence of cellular or molecular events mediating this excitotoxicity. Nuclear factor B (NFB) is a transcription factor involved in regulating inflammatory responses and apoptosis in many cell types. NFB is also associated with intracellular calcium regulation, an important factor in neuronal excitotoxicity. Here, we provide evidence that NFB can play a central role in the degeneration of SGNs. Mice lacking the p50 subunit of NFB (p50 Ϫ/Ϫ mice) showed an accelerated hearing loss with age that was highly associated with an exacerbated excitotoxic-like damage in afferent dendrites under IHCs and an accelerated loss of SGNs. Also, as evidenced by immunostaining intensity, calcium-buffering proteins were significantly elevated in SGNs of the p50 Ϫ/Ϫ mice. Finally, the knock-out mice exhibited an increased sensitivity to low-level noise exposure. The accelerated hearing loss and neural degeneration with age in the p50 Ϫ/Ϫ mice occurred in the absence of concomitant hair cell loss and decline of the endocochlear potential. These results indicate that NFB activity plays an important role in protecting the primary auditory neurons from excitotoxic damage and age-related degeneration. A possible mechanism underlying this protection is that the NFB activity may help to maintain calcium homeostasis in SGNs.

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

Cited by 41 publications

References 35 publications

NF-kappaB-Dependent Apoptotic Hair Cell Death in the Auditory System

NF-kappaB-Dependent Apoptotic Hair Cell Death in the Auditory System

Increased Sensitivity to Noise-Induced Hearing Loss by Blockade of Endogenous PI3K/Akt Signaling

Nuclear Factor κB Deficiency Is Associated with Auditory Nerve Degeneration and Increased Noise-Induced Hearing Loss

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