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This upregulation exhausts intracellular GSH, leading to ROS buildup and oxidative DNA damage that can ultimately generate TP53 mutations, a process that is halted when CHAC1 is knocked down ( TP53 induces ferroptosis primarily by transcriptionally repressing the expression of SLC7A11 ( TP53 lead to a loss of this repression, resulting in sustained SLC7A11 activity and greater cellular resistance to ferroptosis ( 3 KR, which cannot induce cell-cycle arrest, senescence or apoptosis, fully retains the ability to suppress SLC7A11 and trigger ferroptosis under oxidative stress ( The reasons for variable expression of CHAC1 in different cancers are still unclear, but it appears to be critically dependent on TP53 status

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Food Chem Toxicol 44(6):891897 omakl S, Kandemir FM, Kkler S, zdemir S (2022) Morin mitigates ifosfamide induced nephrotoxicity by regulation of NF-kappaB/p53 and Bcl-2 expression

On the other hand, other authors have shown that MPP + induces negative effects in astrocytes, such as loss of viability, impairment of energetic metabolism of mitochondria, ROS generation and decrease in the glutamate clearance by astrocytes [81,85,86]