Dexamethasone treatment of naïve organ of Corti explants alters the expression pattern of apoptosis-related genes

Kimberly N. Hoang, Christine T. Dinh, Esperanza Bas, Shibing Chen, Adrien A. Eshraghi, Thomas R. Van De Water

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Background: Dexamethasone treatment of organ of Corti explants challenged with an ototoxic level of an inflammatory cytokine modulates NFκB signaling and the expression levels of both pro-and anti-apoptosis-related genes. It is not known if naïve organ of Corti explants will respond in a similar manner to treatment with a corticosteroid. This study examines the response of naïve organ of Corti explants to treatment with dexamethasone. Methods: Three-day-old rat organ of Corti explants were cultured for 1, 2, or 4 days. Four-day in vitro cultures were fixed, stained with FITC-phalloidin and hair cells were counted. ELISA was performed on 2-day cultures to determine the levels of phosphorylated nuclear factor kappa B protein. One- and 2-day cultures were studied with real-time RT-PCR for expression levels of β-actin, Bax, Bcl-xl, Bcl-2 and TNFR1 genes with mean fold changes determined with the 2-ΔΔCt method. All mean fold changes in gene and protein expression were analyzed by the Kruskal-Wallis non-parametric test. Results: There were no significant differences in hair cell counts between naïve explants and explants treated with dexamethasone. Dexamethasone treatment of naïve explants resulted in a significant increase (p < 0.01) in the level of phosphorylated-nuclear factor kappa B protein. Bax expression was significantly decreased (p < 0.01) in the dexamethasone-treated explants compared to untreated-naïve explants at 1 and 2 days. TNFR1 expression was significantly reduced in dexamethasone-treated explants at 1 (p < 0.01) and 2 days (p = 0.001). Both Bcl-2 and Bcl-xl expression levels were significantly increased in dexamethasone-treated cultures compared to naïve-cultures at 2 days in vitro (p < 0.001). Dexamethasone-treated explants showed a significant decrease in the Bax/Bcl-2 ratio at both 1 (p = 0.004) and 2 days (p < 0.001) in vitro.

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalBrain Research
Volume1301
DOIs
StatePublished - Nov 16 2009

Keywords

  • Apoptosis
  • Dexamethasone
  • Gene expression
  • Hair cell
  • Organ of Corti
  • Otoprotection

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

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