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Trichostatin A protects against cisplatin-induced ototoxicity by regulating expression of genes related to apoptosis

Ping Wang1, Ping Zhang, Ji Huang

  • 1Department of Otolaryngology-Head and Neck Surgery, First Hospital of Jilin University, Changchun 130021, China.

Neurotoxicology
|April 6, 2013
PubMed
Abstract

Insights

Trichostatin A (TSA) protects against cisplatin-induced ototoxicity by preserving hair cells and spiral ganglion neurons. This histone deacetylase inhibitor modulates genes involved in apoptosis, calcium signaling, and synaptic plasticity, offering a potential therapeutic strategy for hearing loss.

Area of Science:

  • Ototoxicity research
  • Molecular biology
  • Neuroscience

Background:

  • Cisplatin chemotherapy can cause hearing loss (ototoxicity).
  • Histone deacetylase (HDAC) inhibition shows potential for preventing cisplatin-induced ototoxicity.
  • The precise molecular mechanisms underlying this protective effect remain unclear.

Purpose of the Study:

  • To investigate the protective effect of trichostatin A (TSA), an HDAC inhibitor, against cisplatin-induced ototoxicity.
  • To identify differentially expressed genes involved in TSA's protective mechanism.

Main Methods:

  • Organotypic cultures of rat cochlear basilar membranes were treated with cisplatin and/or TSA.
  • Hair cell and spiral ganglion neuron (SGN) survival was assessed.
  • Global gene expression profiling (microarray) identified differentially expressed genes.
  • Real-time quantitative PCR (qPCR) validated gene expression changes.

Main Results:

  • Cisplatin caused significant hair cell and SGN loss, which TSA treatment ameliorated.
  • TSA modulated the expression of numerous genes, including those related to synaptic function, calcium signaling, and apoptosis.
  • TSA upregulated synaptic function genes (e.g., Camk2a, Snap25) downregulated by cisplatin.
  • TSA decreased the expression of apoptosis-related genes (e.g., Tnfrsf1a, Tp53).

Conclusions:

  • TSA demonstrates a protective effect against cisplatin-induced ototoxicity.
  • This protection is mediated by TSA's influence on gene expression critical for apoptosis regulation, calcium homeostasis, neurotransmission, and synaptic plasticity.

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