Event Title

Analysis of High Throughput Gene Array Data Identifies Common Cellular Pathway to Treat Hearing Loss

Session Number

C12

Advisor(s)

Debashree Mukherjea, University of Illinois at Springfield

Location

A-129

Start Date

28-4-2016 1:35 PM

End Date

28-4-2016 2:00 PM

Disciplines

Biology

Abstract

Hearing loss (ototoxicity) is a global phenomenon. Noise induced hearing loss is one of the most common causes. Chemotherapeutic agents such as cisplatin, used in the treatment of solid tumors, also contribute to ototoxicity. We hypothesized that both cisplatin and noise trauma initiate similar stress signaling cascades in the cochlea. The goal of this study was to analyze high throughput gene array data from rat cochleae to determine commonly dysregulated genes in noise and cisplatin induced ototoxicity. Affymetrix expression consoles were used to analyze the genes and the DAVID (the Database for Annotation, Visualization and Integrated Discovery) software was used to generate signaling pathways. Genes from cellular calcium signaling pathways were upregulated under both stress conditions. To validate the calcium signaling pathway, in vitro calcium imaging studies were performed with cultured cochlear hair cells exposed to hydrogen peroxide (H2O2) to mimic the effects of noise and cisplatin in these cultures. H2O2 produced a significant increase in calcium uptake through the transient receptor potential vanilloid 1 (TRPV1) channel, which are present in these cells. Thus, we have identified a common cochlear stress protein (TRPV1) activated by cochlear trauma which could serve as a target for drugs to treat hearing loss.


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Apr 28th, 1:35 PM Apr 28th, 2:00 PM

Analysis of High Throughput Gene Array Data Identifies Common Cellular Pathway to Treat Hearing Loss

A-129

Hearing loss (ototoxicity) is a global phenomenon. Noise induced hearing loss is one of the most common causes. Chemotherapeutic agents such as cisplatin, used in the treatment of solid tumors, also contribute to ototoxicity. We hypothesized that both cisplatin and noise trauma initiate similar stress signaling cascades in the cochlea. The goal of this study was to analyze high throughput gene array data from rat cochleae to determine commonly dysregulated genes in noise and cisplatin induced ototoxicity. Affymetrix expression consoles were used to analyze the genes and the DAVID (the Database for Annotation, Visualization and Integrated Discovery) software was used to generate signaling pathways. Genes from cellular calcium signaling pathways were upregulated under both stress conditions. To validate the calcium signaling pathway, in vitro calcium imaging studies were performed with cultured cochlear hair cells exposed to hydrogen peroxide (H2O2) to mimic the effects of noise and cisplatin in these cultures. H2O2 produced a significant increase in calcium uptake through the transient receptor potential vanilloid 1 (TRPV1) channel, which are present in these cells. Thus, we have identified a common cochlear stress protein (TRPV1) activated by cochlear trauma which could serve as a target for drugs to treat hearing loss.