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.
Lingua originale | English |
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pagine (da-a) | 1-13 |
Numero di pagine | 13 |
Rivista | Antioxidants |
DOI | |
Stato di pubblicazione | Pubblicato - 2018 |
Keywords
- HYDROGEN SULFIDE
- PROTEOMICS