Ferroptosis in Neurons and Cancer Cells Is Similar But Differentially Regulated by Histone Deacetylase Inhibitors

Zille, Marietta; Kumar, Amit; Kundu, Nandini; Bourassa, Megan W.; Wong, Venus; Willis, Dianna E.; Karuppagounder, Saravanan S.; Ratan, Rajiv R.

doi:10.1523/eneuro.0263-18.2019

Cited by 73 publications

(83 citation statements)

References 43 publications

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“…To define an adaptive transcriptional response to ferroptosis, we probed changes in mRNA levels of antioxidant enzymes known to neutralize reactive lipids including GPX4 in primary neurons using a glutamate-induced cell death paradigm now recognized as ferroptosis (Ratan et al, 1994a;Zille et al, 2019) or an in vitro model of ICH involving hemin, which also leads to ferroptosis (Karuppagounder et al, 2016;Zille et al, 2017). As expected, the expression of canonical anti-oxidant enzymes such as superoxide dismutase (SOD2) and catalase were not induced in either paradigm (Figures 1A and 1B).…”

Section: Ferroptotic Stresses and Ich Drive A Frustrated Adaptive Resmentioning

confidence: 99%

“…Ferroptosis was originally identified as a mechanism by which the chemotherapeutic agent, erastin, induced death in KRAS mutant cancer cells (Yagoda et al, 2007). These seminal studies showed that toxicity by erastin, like glutamate or HCA in cortical neurons, is mediated via inhibition of the X c transporter (Zille et al, 2019). Pharmacological or molecular blockade of the X c transporter leads to cellular cystine starvation, depletion of the antioxidant glutathione, and lipid peroxide-induced ferroptosis (Dixon et al, 2012;Ratan et al, 1994a;Yang et al, 2014).…”

Section: Se Prevents Erastin-induced Ferroptosis In Cancer Cells and mentioning

confidence: 99%

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Selenium Drives a Transcriptional Adaptive Program to Block Ferroptosis and Treat Stroke

Alim

Caulfield

Chen

et al. 2019

Cell

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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.

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Section: Ferroptotic Stresses and Ich Drive A Frustrated Adaptive Resmentioning

confidence: 99%

Section: Se Prevents Erastin-induced Ferroptosis In Cancer Cells and mentioning

confidence: 99%

Selenium Drives a Transcriptional Adaptive Program to Block Ferroptosis and Treat Stroke

Alim

Caulfield

Chen

et al. 2019

Cell

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725

502

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“…Studies have found that cells treated with ferric ammonium citrate (FAC) and L-buthionine-sulfoximine (BSO) consistently show reduced GSH-dependent peroxidase activity and increased lipid peroxidation in FRDA disease model (Cotticelli et al, 2019). When comparing the erastin in the induction of ferroptosis in neurons and HT1080 fibrosarcoma cells, it was found that selective protection of neurons by class I histone deacetylase (HDAC) inhibitors and accelerated cancer cell ferroptosis (Zille et al, 2019). Through literature review, it is speculated that in animal models of neurodegenerative diseases, depletion of long-term nuclear receptor-assisted activator (NCOA4) in the brain can worsen the neurodegenerative disease phenotype due to the further inappropriate accumulation of free iron and resulted in oxidative stress (Quiles Del Rey and Mancias, 2019), and then induced ferroptosis in nerve cells.…”

Section: Ferroptosis In Other Neurodegenerative Diseasesmentioning

confidence: 99%

Nrf2 and Ferroptosis: A New Research Direction for Neurodegenerative Diseases

2020

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“…Similar to myoglobin in muscles, neuroglobin is a reserve form of hemoprotein able to store oxygen and protect the brain, at least in part, from hypoxic/ischemic insults [106]. Ferroptosis also plays a role in secondary cell death in hemorrhagic stroke [107,108] and selenium loading can partially prevent ferroptosis in experimental strokes [109].…”

Section: Strokementioning

confidence: 99%

Red Blood Cells and Hemoglobin in Human Atherosclerosis and Related Arterial Diseases

Michel

Martı́n-Ventura

2020

IJMS

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As the main particulate component of the circulating blood, RBCs play major roles in physiological hemodynamics and impact all arterial wall pathologies. RBCs are the main determinant of blood viscosity, defining the frictional forces exerted by the blood on the arterial wall. This function is used in phylogeny and ontogeny of the cardiovascular (CV) system, allowing the acquisition of vasomotricity adapted to local metabolic demands, and systemic arterial pressure after birth. In pathology, RBCs collide with the arterial wall, inducing both local retention of their membranous lipids and local hemolysis, releasing heme-Fe++ with a high toxicity for arterial cells: endothelial and smooth muscle cells (SMCs) cardiomyocytes, neurons, etc. Specifically, overloading of cells by Fe++ promotes cell death. This local hemolysis is an event associated with early and advanced stages of human atherosclerosis. Similarly, the permanent renewal of mural RBC clotting is the major support of oxidation in abdominal aortic aneurysm. In parallel, calcifications promote intramural hemorrhages, and hemorrhages promote an osteoblastic phenotypic shift of arterial wall cells. Different plasma or tissue systems are able, at least in part, to limit this injury by acting at the different levels of this system.

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Ferroptosis in Neurons and Cancer Cells Is Similar But Differentially Regulated by Histone Deacetylase Inhibitors

Abstract: Visual Abstract

Cited by 73 publications

References 43 publications

Selenium Drives a Transcriptional Adaptive Program to Block Ferroptosis and Treat Stroke

Selenium Drives a Transcriptional Adaptive Program to Block Ferroptosis and Treat Stroke

Nrf2 and Ferroptosis: A New Research Direction for Neurodegenerative Diseases

Red Blood Cells and Hemoglobin in Human Atherosclerosis and Related Arterial Diseases

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