TY - JOUR
T1 - Proteomics and Toxicity Analysis of Spinal-Cord Primary Cultures upon Hydrogen Sulfide Treatment
AU - Greco, Viviana
AU - Spalloni, Alida
AU - Corasolla Carregari, Victor
AU - Pieroni, Luisa
AU - Persichilli, Silvia
AU - Mercuri, Nicola B
AU - Urbani, Andrea
AU - Longone, Patrizia
PY - 2018/7/10
Y1 - 2018/7/10
N2 - 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.
AB - 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.
U2 - 10.3390/antiox7070087
DO - 10.3390/antiox7070087
M3 - Article
C2 - 29996549
VL - 7
JO - Antioxidants
JF - Antioxidants
SN - 2076-3921
IS - 7
ER -