Haemin-induced cell death in human monocytic cells is consistent with ferroptosis

Imoto, Shuhei; Kono, Mari; Suzuki, Takashi; Shibuya, Yukiko; Sawamura, Tohru; Mizokoshi, Yuji; Sawada, Hirohide; Ohbuchi, Ayako; Saigo, Katsuyasu

doi:10.1016/j.transci.2018.05.028

Cited by 54 publications

(27 citation statements)

References 18 publications

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“…Moreover, deferasirox has a property of inhibiting nuclear factor kappa B (NFKB) (Messa et al, 2010), indicating that deferasirox may be used for limiting inflammation responses in immune cells. Indeed, deferasirox and DFO inhibit hemin-induced ferroptotic cell death and ROS generation in human monocytes (Imoto et al, 2018), thereby increasing the possibility that iron-dependent ferroptosis is involved in activating inflammation.…”

Section: Deferasiroxmentioning

confidence: 99%

Iron Metabolism in Ferroptosis

Chen

Kang

et al. 2020

Front. Cell Dev. Biol.

594

382

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Ferroptosis is a form of regulated cell death that is characterized by iron-dependent oxidative damage and subsequent plasma membrane ruptures and the release of damage-associated molecular patterns. Due to the role of iron in mediating the production of reactive oxygen species and enzyme activity in lipid peroxidation, ferroptosis is strictly controlled by regulators involved in many aspects of iron metabolism, such as iron uptake, storage, utilization, and efflux. Translational and transcriptional regulation of iron homeostasis provide an integrated network to determine the sensitivity of ferroptosis. Impaired ferroptosis is implicated in various iron-related pathological conditions or diseases, such as cancer, neurodegenerative diseases, and ischemia-reperfusion injury. Understanding the molecular mechanisms underlying the regulation of iron metabolism during ferroptosis may provide effective strategies for the treatment of ferroptosis-associated diseases. Indeed, iron chelators effectively prevent the occurrence of ferroptosis, which may provide new approaches for the treatment of iron-related disorders. In this review, we summarize recent advances in the theoretical modeling of iron-dependent ferroptosis, and highlight the therapeutic implications of iron chelators in diseases.

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Section: Deferasiroxmentioning

confidence: 99%

Iron Metabolism in Ferroptosis

Chen

Kang

et al. 2020

Front. Cell Dev. Biol.

594

382

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“…Intriguingly, the authors point to novel hepatic uptake of Hb-Hp complexes into hepatocytes as an additional clearance mechanism that will need defining. It may be related to the process in rats documented in1972, where 85-95% of the radioactivity from 59 Fe-Hb was present with liver parenchymal cells whether injected IV alone or with Hp [115]. The conclusion was that plasma protein replenishment therapies with both HPX and Hp might be best for SCD patients, especially those with acute chest syndrome.…”

Section: Hemopexin Reduces Inflamation and Descreases Oxidative Stresmentioning

confidence: 97%

“…Interestingly, the bioavailability of heme from the diet as an iron source is superior to that of inorganic iron. However, iron, not heme, is exported into the systemic circulation because after [ 59 Fe]heme is placed in the lumen of isolated rat duodenum, iron-transferrin not heme-HPX is present in the mesenteric vein [13]. This supports extensive catabolism of heme by HOs in duodenal enterocytes.…”

Section: Introductionmentioning

confidence: 92%

“…Human monocytes may also be susceptible to ferroptosis induced by heme in transfusiondependent patients, who often develop iron-overload. When human monocytic THP-1 cells in serum-free medium were incubated for 2 h with 20 µM heme, there was an increase in ROS production together with an increase in cells with markers of necrosis but not markers of apoptosis [59]. The ROS production was prevented by N-acetyl cysteine (which can chelate metals), by iron chelators deferoxamine and deferasirox (the latter being more effective), or an inhibitor of NADPH oxidase that generates ROS.…”

Section: Heme and Iron-dependent Cell Death By Ferroptosismentioning

confidence: 99%

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What Is Next in This “Age” of Heme-Driven Pathology and Protection by Hemopexin? An Update and Links with Iron

2019

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This review provides a synopsis of the published literature over the past two years on the heme-binding protein hemopexin (HPX), with some background information on the biochemistry of the HPX system. One focus is on the mechanisms of heme-driven pathology in the context of heme and iron homeostasis in human health and disease. The heme-binding protein hemopexin is a multi-functional protectant against hemoglobin (Hb)-derived heme toxicity as well as mitigating heme-mediated effects on immune cells, endothelial cells, and stem cells that collectively contribute to driving inflammation, perturbing vascular hemostasis and blood–brain barrier function. Heme toxicity, which may lead to iron toxicity, is recognized increasingly in a wide range of conditions involving hemolysis and immune system activation and, in this review, we highlight some newly identified actions of heme and hemopexin especially in situations where normal processes fail to maintain heme and iron homeostasis. Finally, we present preliminary data showing that the cytokine IL-6 cross talks with activation of the c-Jun N-terminal kinase pathway in response to heme-hemopexin in models of hepatocytes. This indicates another level of complexity in the cell responses to elevated heme via the HPX system when the immune system is activated and/or in the presence of inflammation.

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“…In short, the endogenous inhibition of HSPB1 and CISD1 or changes in the expression of iron metabolism genes can trigger oxidative stress and iron-replete ferroptosis. Likewise, exogenous iron ions obtained from haemin [ 35 ], hemoglobin [ 36 ], and iron-containing nanoparticles [ 37 ] also facilitate iron overload-induced ferroptosis.…”

Section: Oxidative Stress In Ferroptosismentioning

confidence: 99%

Revisiting Tumors and the Cardiovascular System: Mechanistic Intersections and Divergences in Ferroptosis

Wang

Xiang

Zhang

et al. 2020

Oxidative Medicine and Cellular Longevity

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Ferroptosis was recently identified as an iron-dependent regulatory necrosis process mediated by polyunsaturated fatty acid (PUFA) peroxidation. The pivotal events related to oxidative stress in ferroptosis include direct or indirect glutathione peroxidase 4 (GPX4) inhibition, ferrous iron overload, and lipid peroxidation. The links between ferroptosis and multiple pathological processes including tumor and cardiovascular system disease have become increasingly apparent, and the mechanisms and compounds involved in ferroptosis, such as reduction of coenzyme Q10 (ubiquinone/CoQ10), are gradually emerging. Current reports have revealed crossroads between ferroptosis and other multiple responses. This overview of the current research illuminates the mechanisms involving ferroptosis-related compounds and emphasizes the crosstalk between ferroptosis and other responses, including mitochondrial damage, endoplasmic reticulum stress (ER stress), autophagy, and the release of damage-associated molecular patterns (DAMPs), to reveal the intersections of regulatory mechanisms. This review also outlines the discovery, characterization, and pathological relevance of ferroptosis and notes controversial elements in ferroptosis-related mechanisms, such as nuclear factor E2-related factor 2 (Nrf2), sequestosome 1 (p62/SQSTM1), and heat shock protein family A member 5 (HSPA5). We hope our inferences will supply a partial reference for disorder prevention and treatment.

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Haemin-induced cell death in human monocytic cells is consistent with ferroptosis

Cited by 54 publications

References 18 publications

Iron Metabolism in Ferroptosis

Iron Metabolism in Ferroptosis

What Is Next in This “Age” of Heme-Driven Pathology and Protection by Hemopexin? An Update and Links with Iron

Revisiting Tumors and the Cardiovascular System: Mechanistic Intersections and Divergences in Ferroptosis

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