Inner ear supporting cells protect hair cells by secreting HSP70
Lindsey A. May, Inga I. Kramarenko, Carlene S. Brandon, Christina Voelkel-Johnson, Soumen Roy, Kristy Truong, Shimon P. Francis, Elyssa L. Monzack, Fu-Shing Lee, Lisa L. Cunningham
Lindsey A. May, Inga I. Kramarenko, Carlene S. Brandon, Christina Voelkel-Johnson, Soumen Roy, Kristy Truong, Shimon P. Francis, Elyssa L. Monzack, Fu-Shing Lee, Lisa L. Cunningham
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Research Article

Inner ear supporting cells protect hair cells by secreting HSP70

Abstract

Mechanosensory hair cells are the receptor cells of hearing and balance. Hair cells are sensitive to death from exposure to therapeutic drugs with ototoxic side effects, including aminoglycoside antibiotics and cisplatin. We recently showed that the induction of heat shock protein 70 (HSP70) inhibits ototoxic drug–induced hair cell death. Here, we examined the mechanisms underlying the protective effect of HSP70. In response to heat shock, HSP70 was induced in glia-like supporting cells but not in hair cells. Adenovirus-mediated infection of supporting cells with Hsp70 inhibited hair cell death. Coculture with heat-shocked utricles protected nonheat-shocked utricles against hair cell death. When heat-shocked utricles from Hsp70–/– mice were used in cocultures, protection was abolished in both the heat-shocked utricles and the nonheat-shocked utricles. HSP70 was detected by ELISA in the media surrounding heat-shocked utricles, and depletion of HSP70 from the media abolished the protective effect of heat shock, suggesting that HSP70 is secreted by supporting cells. Together our data indicate that supporting cells mediate the protective effect of HSP70 against hair cell death, and they suggest a major role for supporting cells in determining the fate of hair cells exposed to stress.

Authors

Lindsey A. May, Inga I. Kramarenko, Carlene S. Brandon, Christina Voelkel-Johnson, Soumen Roy, Kristy Truong, Shimon P. Francis, Elyssa L. Monzack, Fu-Shing Lee, Lisa L. Cunningham

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Figure 4

Adenoviral infection of supporting cells with HSP70 inhibits neomycin-induced hair cell death.

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Adenoviral infection of supporting cells with HSP70 inhibits neomycin-in...
Utricles were infected with Ad-HSP70 (or Ad-GFP). Under these conditions, the adenovirus infects supporting cells, and no hair cells are infected (see Figure 3). Hair cells are labeled with myosin 7a. (A) Control utricles show normal hair cell numbers. (B) Infection with Ad-GFP does not result in hair cell loss (for clarity, the GFP channel is not shown). (C) Infection with Ad-HSP70 does not result in hair cell loss. (D) Neomycin treatment results in significant loss of hair cells. (E) Infection of supporting cells with Ad-GFP is not protective against neomycin-induced hair cell death. (F) Infection of supporting cells with Ad-HSP70 inhibits neomycin-induced hair cell death. (G) Western blot analysis of HSP70 expression in control and Ad-HSP70–infected utricles. (H) Ad-HSP70 is protective against neomycin-induced hair cell death. 1-way ANOVA, F5,46 = 12.03, P < 0.0001. n = 5–12 utricles per condition. *P < 0.001 between neomycin and neomycin plus Ad-HSP70. Ctrl, control; Neo, neomycin.