Ototoxicity-induced loss of hearing and inner hair cells is attenuated by HSP70 gene transfer
| Autor: | Lisa L. Kabara, Yohei Takada, Donald L. Swiderski, Tomoko Takada, Yehoash Raphael, David F. Dolan, Min Young Lee |
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| Rok vydání: | 2015 |
| Předmět: |
medicine.medical_specialty
lcsh:QH426-470 Immunocytochemistry Audiology Article Ototoxicity Internal medicine Heat shock protein Genetics otorhinolaryngologic diseases Medicine lcsh:QH573-671 Molecular Biology Cochlea business.industry lcsh:Cytology Furosemide medicine.disease Hsp70 lcsh:Genetics Auditory brainstem response Endocrinology medicine.anatomical_structure Organ of Corti Molecular Medicine sense organs business medicine.drug |
| Zdroj: | Molecular Therapy: Methods & Clinical Development, Vol 2, Iss, Pp-(2015) Molecular Therapy. Methods & Clinical Development |
| ISSN: | 2329-0501 |
| DOI: | 10.1038/mtm.2015.19 |
| Popis: | The most common reason for sensorineural deafness is death of hair cells (HCs). Heat shock proteins (HSPs) are molecular chaperones that participate in folding, targeting, and degrading proteins. HSP expression is increased in response to various environmental stresses to protect cells from damage. Here, we tested whether viral-mediated overexpression of HSP70 can protect HCs and hearing from severe ototoxicity (kanamycin and furosemide) in guinea pigs. Adenovirus-HSP70 mCherry (Ad.HSP70-mCherry) was injected to experimental animals and adenovirus-mCherry to controls, 4 days before the ototoxic insult. Hearing thresholds were measured by auditory brainstem response before the insult and again before sacrificing the animals, 14 days after the insult. Epi-fluorescence immunocytochemistry showed that injection of Ad.HSP70-mCherry resulted in mCherry fluorescence in nonsensory cells of the organ of Corti. The ototoxic insult eliminated both outer HCs and inner HCs throughout most of the cochlea of control (adenovirus-mCherry-injected) ears and contralateral (uninjected) ears. Ad.HSP70-mCherry-injected ears exhibited a significant preservation of inner HCs compared to control and contralateral ears, but outer HCs were not protected. Auditory brainstem response thresholds were significantly better in Ad.HSP70-mCherry-injected ears than in control and contralateral ears. Our data show that HSP70 augmentation may represent a potential therapy attenuating ototoxic inner HC loss. |
| Databáze: | OpenAIRE |
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