Abstract
BackgroundHeat 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.MethodsTo address these questions, we used the OC explants isolated from p3-p5 rats. As a read-out, we used RT-PCR, ELISA and immunofluorescence.ResultsWe 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.ConclusionGA 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.
Highlights
Heat shock protein 70 (HSP70) protects inner ear cells from damage and death induced by e.g. heat or toxins
The effect of geldanamycin on hair cells To determine if GA is safe for use in OC explant cultures and has no cytotoxic effects on hair cells, we treated OC explants for 24 h with GA at varying concentration, which we chose based on the literature [16,18]
We have found that GA does not affect the numbers of inner hair cells (IHCs) (Fig. 1A) and outer hair cells (OHCs) (Fig. 1B) in apical, middle or basal part of OC, as compared to the untreated controls
Summary
Heat shock protein 70 (HSP70) protects inner ear cells from damage and death induced by e.g. heat or toxins. The constitutively expressed HSP70 (70 kDa heat shock cognate protein, HSC70) functions as chaperone during protein synthesis, intracellular transport and degradation Under stress conditions, such as hyperthermia, oxidative stress, inflammation, exercise, exposure to toxins and ultraviolet. Journal of Biomedical Science 2009, 16:79 http://www.jbiomedsci.com/content/16/1/79 light, starvation, hypoxia, or water deprivation, inducible HSP70 (iHSP70, HSP72) provide cellular protection by repairing the damaged proteins in cytoplasm and by blocking apoptosis [1,2]. Experiments with knock-out Hsf1-/and Hsp70-/- mice, demonstrated that the expression of HSP70 is necessary to protect the cochlear hair cells from noise exposure and aminoglycoside ototoxicity [10,11]
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