Ferroptosis-IN-23 exerts a synergistic effect by simultaneously activating Steap4 and glutathione peroxidase 4 ( GPX4 ), thereby maintaining iron metabolism homeostasis
Figures 1B , 3 ), resulting in down-regulation of the hepatic GHR expression, as inferred from reductions in circulating levels of GHBP (59), and decreased GH binding (60)
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The first step of glutathione synthesis involves the formation of glutamylcysteine from glutamate and cysteine in an ATP dependent reaction catalysed by glutamate-cysteine-ligase (GCL) which requires either Mg 2+ or Mn 2+ as a cofactor
As a consequence, both oxygen and iron deprivation promote HIF stability and modulate expression of genes involved in cell cycle progression, proliferation, iron homeostasis and metabolic adaptation [22]
