- 作者: Yang Yu, Agnieszka J Szczepek, Heidemarie Haupt, Birgit Mazurek
- 作者服務機構: Molecular Biology Research Laboratory and Tinnitus Center, Department of Otorhinolaryngology, Charite - Universitatsmedizin Berlin, Campus Charite Mitte, Berlin, Germany
- 中文摘要: --
- 英文摘要:
Background : Heat shock protein 70 (HSP70) protects inner ear cells from damage and death induced by e.g.
heat or toxins. Benzoquinone ansamycin antibiotic geldanamycin (GA) was demonstrated to
induce the expression of HSP70 in various animal cell types. The aim of our study was to
investigate whether GA induces HSP70 in the organ of Corti (OC), which contains the auditory
sensory cells, and whether GA can protect these cells from toxicity caused by a common
aminoglycoside antibiotic gentamicin.
Methods : To address these questions, we used the OC explants isolated from p3-p5 rats. As a read-out, we
used RT-PCR, ELISA and immunofluorescence.
Results : We found that GA at the concentration of 2 μM efficiently induced HSP70 expression on mRNA
and protein level in the OC explants. Confocal microscopy revealed that HSP70 induced by GA
is expressed by hair cells and interdental cells of spiral limbus. Preincubation of explants with
2 μM GA prior to adding gentamicin (500 μM) significantly reduced the loss of outer but not
inner hair cells, suggesting different mechanisms of otoprotection needed for these two cell types.
Conclusions : GA induced HSP70 in the auditory sensory cells and partially protected them from toxicity of
gentamicin. Understanding the molecular mechanisms of GA otoprotection may provide insights
for preventative therapy of the hearing loss caused by aminoglycoside antibiotics. - 中文關鍵字: --
- 英文關鍵字: --