Xu, Yang; Li, Yuting; Li, Jiaxin; Chen, Wei published the artcile< Ethyl carbamate triggers ferroptosis in liver through inhibiting GSH synthesis and suppressing Nrf2 activation>, Product Details of C15H22N2O2, the main research area is ethyl carbamate GSH Nrf2 ferroptosis oxidative stress toxicity; Ethyl carbamate; Ferroptosis; GSH depletion; Lipid peroxidation; Nrf2.
Humans are inevitably exposed to Et carbamate (EC) via consumption of fermented food and beverages. EC, known as an environmental toxin, can cause oxidative stress-mediated severe toxicity, but the underlying mechanisms remain unveiled. Ferroptosis is a newly identified ROS-mediated non-apoptotic cell death characterized by iron accumulation and excessive lipid oxidation In this study, we first found that EC triggered ferroptosis in liver cells by detection of decreased cell viability, GSH, GPX4 and Ferritin levels, as well as increased iron and MDA contents. Ferroptosis inhibitor ferrostatin-1 (Fer-1) pretreatment rescued ferroptotic damage, indicating that ferroptosis was critical for EC-caused cell death. Furthermore, GSH synthesis precursor N-acetylcysteine displayed significant anti-ferroptotic properties and we suggested that GSH depletion might be the main cause of ferroptosis under EC exposure. EC-triggered GSH depletion mainly depended on suppressed GSH synthesis via inhibition of SLC7A11 and GCLC expressions. Notably, EC blocked Nrf2 activation by repression of phosphorylation modification and nuclear translocation, which further resulted in ferroptosis occurrence. We also observed EC-induced liver dysfunction and inflammation, accompanied with oxidative stress, ferroptosis and downregulated Nrf2 signaling in Balb/c mice, which could be effectively reversed by Fer-1 and tBHQ pretreatment. Together, our study indicated that ferroptosis is a new mechanism for EC-caused toxicity, which was attributed to Nrf2 inactivation and GSH depletion.
Redox Biology published new progress about Cell viability. 347174-05-4 belongs to class esters-buliding-blocks, and the molecular formula is C15H22N2O2, Product Details of C15H22N2O2.
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