Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews...
    • Mechanisms Underlying the Metabolic Syndrome (Oct 2019)
    • Reparative Immunology (Jul 2019)
    • Allergy (Apr 2019)
    • Biology of familial cancer predisposition syndromes (Feb 2019)
    • Mitochondrial dysfunction in disease (Aug 2018)
    • Lipid mediators of disease (Jul 2018)
    • Cellular senescence in human disease (Apr 2018)
    • View all review series...
  • Collections
    • Recently published
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Scientific Show Stoppers
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • About
  • Editors
  • Consulting Editors
  • For authors
  • Current issue
  • Past issues
  • By specialty
  • Subscribe
  • Alerts
  • Advertise
  • Contact
  • Conversations with Giants in Medicine
  • Author's Takes
  • Recently published
  • Brief Reports
  • Technical Advances
  • Commentaries
  • Editorials
  • Hindsight
  • Review series
  • Reviews
  • The Attending Physician
  • First Author Perspectives
  • Scientific Show Stoppers
  • Top read articles
  • Concise Communication
Inner ear supporting cells protect hair cells by secreting HSP70
Lindsey A. May, … , Fu-Shing Lee, Lisa L. Cunningham
Lindsey A. May, … , Fu-Shing Lee, Lisa L. Cunningham
Published August 1, 2013; First published July 25, 2013
Citation Information: J Clin Invest. 2013;123(8):3577-3587. https://doi.org/10.1172/JCI68480.
View: Text | PDF
Category: Research Article

Inner ear supporting cells protect hair cells by secreting HSP70

  • Text
  • PDF
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

×

Figure 9

Ad-HSP70-mCherry is protective, and it is not internalized by hair cells.

Options: View larger image (or click on image) Download as PowerPoint
Ad-HSP70-mCherry is protective, and it is not internalized by hair cells...
(A) Supporting cells were infected with Ad-HSP70-mCherry (or Ad-mCherry as a control). Infected utricles were cultured in the presence or absence of neomycin (3 mM). Neither virus resulted in significant hair cell death, while neomycin caused a significant loss of hair cells. Infection of supporting cells with Ad-HSP70-mCherry inhibited neomycin-induced hair cell death (ANOVA, *P < 0.05). Infection of supporting cells with Ad-mCherry was not protective. n = 6–11 utricles per condition. (B) Utricles infected with Ad-HSP70-mCherry were fixed, and hair cells were labeled using antimyosin 7a (green). Utricles were examined using confocal microscopy (original magnification, ×63). Schematic shows the location of each panel. Upper panels show confocal images taken at the level of the hair cell cuticular plates, while the lower panels show confocal images from the same field taken at the level of the hair cell nuclei. Ad-HSP70-mCherry (red) is restricted to supporting cells and does not colocalize with myosin 7a (green, hair cells), indicating that Ad-HSP70-mCherry does not translocate from supporting cells to hair cells. Scale bars: 20 μm.
Follow JCI:
Copyright © 2019 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts