Geldanamycin induces production of heat shock protein 70 and partially attenuates ototoxicity caused by gentamicin in the organ of Corti explants

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.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.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.Heat shock proteins (HSPs) are a group of highly conserved proteins produced by all living organisms. HSPs maintain cellular homeostasis and are involved in the response to various stresses. The family of 70 kDa heat shock proteins (HSP70) are ubiquitously expressed HSPs. Under normal physiological circumstances, 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 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]. Consequently, the heat shock proteins are also referred to as stress proteins and their up-regulation is sometimes described more generally as a part of stress response. The major stress-inducible isoform of HSP70 is encoded by two genes - Hsp70-1 (Hspa1b) and Hsp70-2 (Hspa1a) [3]. The expression of Hsp70-1 and Hsp70-2 is re