Proteomics and toxicity analysis of spinal-cord primary cultures upon hydrogen sulfide treatment

Viviana Greco, Alida Spalloni, Victor Corasolla Carregari, Luisa Pieroni, Silvia Persichilli, Nicola B. Mercuri, Andrea Urbani, Patrizia Longone

Research output: Contribution to journalArticle

Abstract

Hydrogen sulfide (H2S) is an endogenous gasotransmitter recognized as an essential body product with a dual, biphasic action. It can function as an antioxidant and a cytoprotective, but also as a poison with a high probability of causing brain damage when present at noxious levels. In a previous study, we measured toxic liquoral levels of H2S in sporadic amyotrophic lateral sclerosis (ALS) patients and in the familial ALS (fALS) mouse model, SOD1G93A. In addition, we experimentally demonstrated that H2S is extremely and selectively toxic to motor neurons, and that it is released by glial cells and increases Ca2+concentration in motor neurons due to a lack of ATP. The presented study further examines the effect of toxic concentrations of H2S on embryonic mouse spinal-cord cultures. We performed a proteomic analysis that revealed a significant H2S-mediated activation of pathways related to oxidative stress and cell death, particularly the Nrf-2-mediated oxidative stress response and peroxiredoxins. Furthermore, we report that Na2S (a stable precursor of H2S) toxicity is, at least in part, reverted by the Bax inhibitor V5 and by necrostatin, a potent necroptosis inhibitor.

Original languageEnglish
Article number87
JournalAntioxidants
Volume7
Issue number7
DOIs
Publication statusPublished - Jul 10 2018

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Keywords

  • Apoptosis
  • Hydrogen sulfide
  • Motor neuron
  • Necroptosis
  • Proteomics

ASJC Scopus subject areas

  • Physiology
  • Biochemistry
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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