Activation of autophagic flux and the Nrf2/ARE signaling pathway by hydrogen sulfide protects against acrylonitrile-induced neurotoxicity in primary rat astrocytes

摘要: Hydrogen sulfide (H2S), the third gasotransmitter, has been shown to act as a neuroprotective factor in numerous pathological processes; however, its underlying mechanism(s) of action remain unclear. It is widely accepted that activation moderate autophagy and Nrf2/ARE signaling pathway play important roles biological self-defense systems. In present study, we investigated whether exogenous H2S protects against cytotoxicity acrylonitrile (AN), neurotoxin, primary rat astrocytes. We found pretreatment for 1 h with sodium hydrosulfide (NaHS), donor (200–800 µM), significantly attenuated AN-induced decrease cell viability, increase lactate dehydrogenase release morphological changes. Furthermore, NaHS oxidative stress by reducing reactive oxygen species (ROS) levels increasing glutathione (GSH) concentration. Moreover, activated autophagic flux, detectable change autophagy-related proteins (Beclin-1, Atg5 p62), formation acidic vesicular organelles LC3B aggregation, confirmed adenoviral expression mRFP–GFP–LC3. Additionally, stimulated translocation Nrf2 into nucleus increased heme oxygenase-1 γ-glutamylcysteine synthetase, downstream targets Nrf2. Notably, inhibitor 3-methyladenine Beclin-1, or Nrf2-targeted siRNA, effects neurotoxicity. conclusion, identified crucial role of  H2S-mediated neuroprotection toxicity Our findings provide novel insights mechanisms neuroprotection, suggest H2S-based donors may serve potential new candidate drugs treat