Selenium Drives a Transcriptional Adaptive Program to Block Ferroptosis and Treat Stroke.
By I. Alim, J.T. Caulfield, Yingxin Chen, V. Swarup, R. Ratan. Cell, 2019
868 citations recorded by the source corpus.
Ferroptosis, a non-apoptotic form of programmed cell death, is triggered by oxidative stress in cancer, heat stress in plants, and hemorrhagic stroke. A homeostatic transcriptional response to ferroptotic stimuli is unknown. We show that neurons respond to ferroptotic stimuli by induction of selenoproteins, including antioxidant glutathione peroxidase 4 (GPX4). Pharmacological selenium (Se) augments GPX4 and other genes in this transcriptional program, the selenome, via coordinated activation of the transcription factors TFAP2c and Sp1 to protect neurons. Remarkably, a single dose of Se delivered into the brain drives antioxidant GPX4 expression, protects neurons, and improves behavior in a hemorrhagic stroke model. Altogether, we show that pharmacological Se supplementation effectively inhibits GPX4-dependent ferroptotic death as well as cell death induced by excitotoxicity or ER stress, which are GPX4 independent. Systemic administration of a brain-penetrant selenopeptide activates homeostatic transcription to inhibit cell death and improves function when delivered after hemorrhagic or ischemic stroke.
Subfields: Obstetrics and Gynecology, Pulmonary and Respiratory Medicine, Surgery
View Paper: https://www.semanticscholar.org/paper/57465344cfcfe00aa06750ee9f7ccf38898b0f1f
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In Pulmonary and Respiratory Medicine
Citations in the corpus
- Mechanisms of neuronal cell death in ischemic stroke and their therapeutic implications (2021, background): “Selenium‐containing compounds have also been shown to reduce infarct volume significantly in the MCAO mouse model.(183,424) Guan et al.”
- Ferroptosis: mechanisms and links with diseases (2021, background): “Pharmacological selenium significantly reduces infarct volume by driving an adaptive transcriptional program to block ferroptosis.(247) The inhibition of glutaminolysis, involved in the NADPHGSH-GPx4 pathway, can attenuate cardiac IRI by blocking ferroptosis.”
- Ferroptosis turns 10: Emerging mechanisms, physiological functions, and therapeutic applications. (2022, neutral): “Selenium delivery suppresses ferroptosis during stroke (Alim et al., 2019).”