AIF knockdown induce apoptosis and mitochondrial dysfunction in cochlear spiral ganglion neurons in vitro

Mol Med Rep. 2020 Apr;21(4):1910-1920. doi: 10.3892/mmr.2020.10970. Epub 2020 Jan 31.

Abstract

The underlying mechanism involved in auditory neuropathy spectrum disorder (ANSD) remains largely unclear. It has been previously reported that mutations in the apoptosis‑inducing factor (AIF) gene are associated with auditory neuropathy and delayed peripheral neuropathy, which can eventually cause ANSD. In the present study, the regulatory effects of AIF knockdown on the cellular functions of spiral ganglion neurons (SNGs) and the molecular mechanism(s) of AIF knockdown in inducing cell apoptosis in SGNs were further investigated. The results showed that the AIF knockdown via siRNA transfection resulted in high levels of oxidative stress, and impaired mitochondrial respiration activity and membrane potential in SGNs. Western blotting further proved that the knockdown of AIF can decrease the content of anti‑apoptotic and anti‑oxidative proteins, as well as mitochondrial respiratory chain Complex I proteins. The present experimental data suggested that the abnormal expression of AIF may affect SGNs cellular function, and may contribute to the progress of ANSD.

Keywords: aiF; auditory neuropathy spectrum disorder; sirna knockdown; cochlear spiral ganglion neurons; cellular dysfunction.

MeSH terms

  • Adenosine Triphosphate / biosynthesis
  • Animals
  • Apoptosis Inducing Factor / metabolism*
  • Apoptosis*
  • Cell Respiration
  • Cells, Cultured
  • Cochlea / metabolism*
  • Gene Knockdown Techniques*
  • Mitochondria / metabolism*
  • Neurons / metabolism*
  • Neurons / pathology
  • Oxidation-Reduction
  • Oxidative Stress
  • Poly Adenosine Diphosphate Ribose / metabolism
  • Poly(ADP-ribose) Polymerases / metabolism
  • Rats, Sprague-Dawley
  • Spiral Ganglion / metabolism*
  • Spiral Ganglion / pathology

Substances

  • Apoptosis Inducing Factor
  • Poly Adenosine Diphosphate Ribose
  • Adenosine Triphosphate
  • Poly(ADP-ribose) Polymerases