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Article Dans Une Revue Redox Biology Année : 2023

Thiosulfate sulfurtransferase deficiency promotes oxidative distress and aberrant NRF2 function in the brain

Résumé

Thiosulfate sulfurtransferase (TST, EC 2.8.1.1) was discovered as an enzyme that detoxifies cyanide by conversion to thiocyanate (rhodanide) using thiosulfate as substrate; this rhodanese activity was subsequently identified to be almost exclusively located in mitochondria. More recently, the emphasis regarding its function has shifted to hydrogen sulfide metabolism, antioxidant defense, and mitochondrial function in the context of protective biological processes against oxidative distress. While TST has been described to play an important role in liver and colon, its function in the brain remains obscure. In the present study, we therefore sought to address its potential involvement in maintaining cerebral redox balance in a murine model of global TST deficiency (Tst−/− mice), primarily focusing on characterizing the biochemical phenotype of TST loss in relation to neuronal activity and sensitivity to oxidative stress under basal conditions. Here, we show that TST deficiency is associated with a perturbation of the reactive species interactome in the brain cortex secondary to altered ROS and RSS (specifically, polysulfide) generation as well as mitochondrial OXPHOS remodeling. These changes were accompanied by aberrant Nrf2-Keap1 expression and thiol-dependent antioxidant function. Upon challenging mice with the redox-active herbicide paraquat (25 mg/kg i.p. for 24 h), Tst−/− mice displayed a lower antioxidant capacity compared to wildtype controls (C57BL/6J mice). These results provide a first glimpse into the molecular and metabolic changes of TST deficiency in the brain and suggest that pathophysiological conditions associated with aberrant TST expression and/or activity renders neurons more susceptible to oxidative stress-related malfunction.
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Dates et versions

hal-04294976 , version 1 (20-11-2023)

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Paternité - Pas d'utilisation commerciale - Pas de modification

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Yang Luo, Laurent Chatre, Shaden Melhem, Zayana M Al-Dahmani, Natalie Z.M. Homer, et al.. Thiosulfate sulfurtransferase deficiency promotes oxidative distress and aberrant NRF2 function in the brain. Redox Biology, 2023, 68, pp.102965. ⟨10.1016/j.redox.2023.102965⟩. ⟨hal-04294976⟩
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