Cell lines in inner ear research

Rivolta, Marcelo N.; Holley, Matthew C.

doi:10.1002/neu.10111

Cited by 63 publications

(39 citation statements)

References 88 publications

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“…OC-2 cells show expression of both supporting cell and hair cell markers, including Pou4f3, and are commonly used as an in vitro system to study the auditory sensory epithelium (Rivolta and Holley, 2002). We manipulated endogenous Pou4f3 levels in OC-2 cells (cultured under proliferating conditions) by transfecting them with either a Pou4f3 expression vector or an antisense Pou4f3 construct.…”

Section: Identification Of Caprin-1 As a Downstream Target Of Pou4f3mentioning

confidence: 99%

Caprin-1 is a target of the deafness genePou4f3and is recruited to stress granules in cochlear hair cells in response to ototoxic damage

Towers¹,

Kelly²,

Sud³

et al. 2011

Journal of Cell Science

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The POU4 family of transcription factors are required for survival of specific cell types in different sensory systems. Pou4f3 is essential for the survival of auditory sensory hair cells and several mutations in human POU4F3 cause hearing loss. Thus, genes regulated by Pou4f3 are likely to be essential for hair cell survival. We performed a subtractive hybridisation screen in an inner-ear-derived cell line to find genes with differential expression in response to changes in Pou4f3 levels. The screen identified the stress-granule-associated protein Caprin-1 as being downregulated by Pou4f3. We demonstrated that this regulation occurs through the direct interaction of Pou4f3 with binding sites in the Caprin-1 5′ flanking sequence, and describe the expression pattern of Caprin-1 mRNA and protein in the cochlea. Moreover, we found Caprin-1-containing stress granules are induced in cochlear hair cells following aminoglycoside-induced damage. This is the first report of stress granule formation in mammalian hair cells and suggests that the formation of Caprin-1-containing stress granules is a key damage response to a clinically relevant ototoxic agent. Our results have implications for the understanding of aminoglycoside-induced hearing loss and provide further evidence that stress granule formation is a fundamental cellular stress response.

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Section: Identification Of Caprin-1 As a Downstream Target Of Pou4f3mentioning

confidence: 99%

Caprin-1 is a target of the deafness genePou4f3and is recruited to stress granules in cochlear hair cells in response to ototoxic damage

Towers¹,

Kelly²,

Sud³

et al. 2011

Journal of Cell Science

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“…One reason could be due to the fact that research on the cellular and molecular mechanisms involved is frequently limited by a small amount of cochlear tissue available for study, a limitation that could potentially be overcome by the use of cochlear cell lines. In recent years, immortalized cell lines derived from the mouse Organ of Corti have been developed and characterised [13]. For example, the OC-k3 cell line is derived from the Organ of Corti of the transgenic mouse.…”

Section: Introductionmentioning

confidence: 99%

Dose-dependant radiation-induced apoptosis in a cochlear cell-line

et al. 2006

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Cisplatin and gentamycin are both ototoxic and they have been shown to induce cochlear cell apoptosis. Although radiation is also ototoxic, radiation-induced apoptosis in cochlear cells has not been studied. This study aimed to investigate the biophysical changes of dose-related radiation-induced cochlear cell apoptosis in an experimental model. Post gamma-irradiation apoptosis was demonstrated in the cochlear cell-line OC-k3 by flow cytometry and TUNEL assay. This was dose-dependant with enhanced apoptosis resulting after 20 than 5 Gy, and occurred predominantly at 72 h post-irradiation. Microarray analysis showed associated dose-dependant apoptotic gene regulation changes. Western blotting revealed p53 up-regulation of at 72 h and phosphorylation at 3, 24, 48 and 72 h after irradiation. Early activation of c-jun occurred at 3 h, but was not sustained with time. Associated dose-dependant intracellular generation of reactive oxygen species (ROS) was also demonstrated using 2', 7'-dichlorofluorescein diacetate. In conclusion, this study demonstrated a dose-dependant cochlear cell apoptosis and associated ROS generation after irradiation, with p53 possibly playing a key role. Based on this ROS-linked apoptotic model, anti-oxidants and anti-apoptotic factors could potentially be used to prevent radiation-induced sensori-neural hearing loss. As these medications can be delivered topically through the middle ear, their systematic side effects could therefore be minimized.

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“…A multipotent cell line, for example, has been described whose cells were derived from the developing otocyst of a transgenic mouse (H-2Kb-tsA58). The cells can be maintained in a proliferating, undifferentiated state in vitro in the presence of g-interferon [124,125]. These cells can then be manipulated to differentiate into sensory hair cells when transfected to over-express the mammalian atonal' homolog (Math-1) gene product [126,127].…”

Section: Conclusion: Clinical Implications Of Understanding Moleculamentioning

confidence: 99%

Hearing molecules: contributions from genetic deafness

Eisen¹,

Ryugo²

2007

Cell. Mol. Life Sci.

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Considerable progress has been made over the past decade identifying many genes associated with deafness. With the identification of these hereditary deafness genes and the proteins they encode, molecular elements of basic hearing mechanisms emerge. As functional studies of these molecular elements become available, we can put together the pieces of the puzzle and begin to reach an understanding of the molecular mechanisms of hearing. The goal of this review is to discuss studies over the past decade that address the function of the proteins implicated in genetic deafness and to place them in the context of basic molecular mechanisms in hearing. The first part of this review highlights structural and functional features of the cochlea and auditory nerve. This background will provide a context for the second part, which addresses the molecular mechanisms underlying cochlear function as elucidated by genetic causes of deafness.

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Cell lines in inner ear research

Cited by 63 publications

References 88 publications

Caprin-1 is a target of the deafness genePou4f3and is recruited to stress granules in cochlear hair cells in response to ototoxic damage

Caprin-1 is a target of the deafness genePou4f3and is recruited to stress granules in cochlear hair cells in response to ototoxic damage

Dose-dependant radiation-induced apoptosis in a cochlear cell-line

Hearing molecules: contributions from genetic deafness

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