The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Rescue of Hearing, Auditory Hair Cells, and Neurons by CEP-1347/KT7515, an Inhibitor of c-Jun N-Terminal Kinase Activation
Open accessAbstract
We have studied the mechanisms of auditory hair cell death after insults in vitro and in vivo. We show DNA fragmentation of hair cell nuclei after ototoxic drug and intense noise trauma. By using phospho-specific c-Jun-N-terminal kinase (JNK) and c-Jun antibodies in immunohistochemistry, we show that the JNK pathway, associated with stress, injury, and apoptosis, is activated in hair cells after trauma. CEP-1347, a derivative of the indolocarbazole K252a, is a small molecule that has been shown to attenuate neurodegeneration by blocking the activation of JNK (Maroney et al., 1998). Subcutaneously delivered CEP-1347 attenuated noise-induced hearing loss. The protective effect was demonstrated by functional tests, which showed less hearing threshold shift in CEP-1347-treated than in nontreated guinea pigs, and by morphometric methods showing less hair cell death in CEP-1347-treated cochleas. In organotypic cochlear cultures, CEP-1347 prevented neomycin-induced hair cell death. In addition to hair cells, CEP-1347 promoted survival of dissociated cochlear neurons. These results suggest that therapeutic intervention in the JNK signaling cascade, possibly by using CEP-1347, may offer opportunities to treat inner ear injuries.
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Cites
A Cytoplasmic Inhibitor of the JNK Signal Transduction Pathway
Dickens, M., Rogers, J. S., Cavanagh, J., Raitano, A., Xia, Z., Halpern, J. R., Greenberg, M. E., Sawyers, C. L., & Davis, R. J. (1997) · Science · doi:10.1126/science.277.5326.693 · Cited by 675
Cited by
Therapeutic strategies for rheumatoid arthritis
Smolen, J. S., & Steiner, G. (2003) · Nature Reviews Drug Discovery · doi:10.1038/nrd1109 · Cited by 911
The Role of Oxidative Stress in Noise-Induced Hearing Loss
Henderson, D., Bielefeld, E. C., Harris, K. C., & Hu, B. H. (2006) · Ear & Hearing · doi:10.1097/01.aud.0000191942.36672.f3 · Cited by 879
Harris, J. A., Cheng, A. G., Cunningham, L. L., MacDonald, G., Raible, D. W., & Rubel, E. W. (2003) · JARO - Journal of the Association for Research in Otolaryngology · doi:10.1007/s10162-002-3022-x · Cited by 462
Delayed production of free radicals following noise exposure
Yamashita, D., Jiang, H.-Y., Schacht, J., & Miller, J. M. (2004) · Brain Research · doi:10.1016/j.brainres.2004.05.104 · Cited by 352
Metadata
- Authors
- Pirvola, U., Xing-Qun, L., Virkkala, J., Saarma, M., Murakata, C., Camoratto, A. M., Walton, K. M., & Ylikoski, J.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2000-01-01
- Volume
- 20
- Issue
- 1
- Pages
- 43-50
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- OpenAlex
- W1918125126
- Cited by
- 307
- References
- 1
- FWCI
- 6.36
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- The paper
- Pirvola, U., Xing-Qun, L., Virkkala, J., Saarma, M., Murakata, C., Camoratto, A. M., Walton, K. M., & Ylikoski, J. (2000). Rescue of Hearing, Auditory Hair Cells, and Neurons by CEP-1347/KT7515, an Inhibitor of c-Jun N-Terminal Kinase Activation. The Journal of Neuroscience. https://doi.org/10.1523/jneurosci.20-01-00043.2000
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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