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Related Concept Videos

Western Blotting01:15

Western Blotting

Western blotting is an analytical technique for protein identification. It has various applications in immunology and medicine, including detecting diseases like bovine spongiform encephalopathy, mad cow disease, and human and feline immunodeficiency virus from biological samples.
The technique begins with separating proteins from the sample using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), followed by protein transfer, immunoblotting, and finally, protein detection.

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Quantitative profiling of cochlear synaptosomal proteins in cisplatin-induced synaptic dysfunction.

Monazza Shahab1, Rita Rosati2, Paul M Stemmer2

  • 1Department of Pharmacology, Wayne State University, Detroit, MI, USA; Institute of Environment Health Science, Wayne State University, Detroit, MI, USA.

Hearing Research
|May 5, 2024
PubMed
Summary

Cisplatin damages cochlear ribbon synapses, impairing hearing. Targeting nitrative stress with MnTBAP protected against this cisplatin-induced synaptic dysfunction and hearing loss.

Keywords:
CisplatinCochlear synaptosomeMnTBAP chlorideNitrative stressOtotoxicitySynaptic dysfunction

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Area of Science:

  • Oto-neuroscience
  • Molecular Biology
  • Toxicology

Background:

  • Cochlear ribbon synapse disruption impairs auditory signal transmission.
  • Cisplatin is known to cause ribbon synapse loss, but the mechanism is unclear.
  • Nitrative stress is implicated in cochlear dysfunction.

Purpose of the Study:

  • To investigate if cisplatin alters cochlear synaptosomal protein abundance.
  • To determine if targeting nitrative stress can prevent cisplatin-induced synaptic dysfunction.

Main Methods:

  • Auditory brainstem response (ABR) testing in mice treated with cisplatin.
  • Mass spectrometry to analyze cochlear synaptosomal proteins.
  • Pathway analysis of dysregulated proteins.
  • Co-treatment with MnTBAP, a peroxynitrite scavenger.

Main Results:

  • Cisplatin induced synaptic dysfunction, evidenced by altered ABR wave I amplitude and latency.
  • 102 proteins decreased and 249 increased in abundance post-cisplatin treatment.
  • Dysregulated proteins were involved in calcium binding, ion regulation, synapses, and endocytosis.
  • MnTBAP treatment attenuated cisplatin-induced protein changes and prevented ABR waveform alterations.

Conclusions:

  • Cisplatin alters cochlear synaptosomal protein expression.
  • Oxidative/nitrative stress plays a role in cisplatin-induced cochlear synaptopathy.
  • Targeting nitrative stress may offer a therapeutic strategy against cisplatin ototoxicity.