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Mechanism of cystathionine-β-synthase inhibition by disulfiram : The role of bis(N,N-diethyldithiocarbamate)-copper(II)

Zuhra, Karim ; Panagaki, Theodora ; B.Randi, Elisa ; Augsburger, Fiona ; Blondel, Marc ; Friocourt, Gaelle ; Herault, Yann ; Szabo, Csaba

In: Biochemical Pharmacology, 2020, vol. 182, p. 114267

Background: Hydrogen sulfide (H2S) is an endogenous mammalian gasotransmitter. Cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE) and 3- mercaptopyruvate sulfurtransferase (3-MST) are the principal enzymes responsible for its biogenesis. A recent yeast screen suggested that disulfiram (a well-known inhibitor of aldehyde dehydrogenase and a clinically used drug in the treatment of...

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Overproduction of H2S, generated by CBS, inhibits mitochondrial Complex IV and suppresses oxidative phosphorylation in Down syndrome

Panagaki, Theodora ; Randi, Elisa B. ; Augsburger, Fiona ; Szabo, Csaba

In: Proceedings of the National Academy of Sciences, 2019, p. 201911895

Down syndrome (DS) is associated with significant perturbances in mitochondrial function. Here we tested the hypothesis that the suppression of mitochondrial electron transport in DS cells is due to high expression of cystathionine-β-synthase (CBS) and subsequent overproduction of the gaseous transmitter hydrogen sulfide (H2S). Fibroblasts from DS individuals showed higher CBS expression...

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