Inhibition of ferroptosis promotes megakaryocyte differentiation and platelet production

Song, Baoquan; Miao, Wenjing; Cui, Qingya; Shi, Bingyu; Zhang, Jian; Qiu, Huiying; Zhang, Leisheng; Han, Yue

doi:10.1111/jcmm.17289

Cited by 7 publications

(5 citation statements)

References 10 publications

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“…However, damaged erythrocytes under severe hemolytic anemia lead to more serious erythrophagocytosis by splenic red pulp macrophages (RPM) [30]. Similarly, patients with liver cirrhosis were shown to have lower serum and hepatic transferrin, resulting in iron overloading and ferroptosis in multiple organs [37][38][39]. Our recent findings on LPA 3 activation restoring erythrocyte numbers under acute hemolytic anemia conditions suggest a potential therapeutic avenue for reducing systemic ferroptosis in aging-induced anemia [15].…”

Section: Discussionmentioning

confidence: 93%

Lysophosphatidic Acid Receptor 3 Activation Is Involved in the Regulation of Ferroptosis

Huang,

Lin,

Chiang

et al. 2024

IJMS

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Ferroptosis, a unique form of programmed cell death trigged by lipid peroxidation and iron accumulation, has been implicated in embryonic erythropoiesis and aging. Our previous research demonstrated that lysophosphatidic acid receptor 3 (LPA3) activation mitigated oxidative stress in progeria cells and accelerated the recovery of acute anemia in mice. Given that both processes involve iron metabolism, we hypothesized that LPA3 activation might mediate cellular ferroptosis. In this study, we used an LPA3 agonist, 1-Oleoyl-2-O-methyl-rac-glycerophosphothionate (OMPT), to activate LPA3 and examine its effects on the ferroptosis process. OMPT treatment elevated anti-ferroptosis gene protein expression, including solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), heme oxygenase-1 (HO-1), and ferritin heavy chain (FTH1), in erastin-induced cells. Furthermore, OMPT reduced lipid peroxidation and intracellular ferrous iron accumulation, as evidenced by C11 BODIPY™ 581/591 Lipid Peroxidation Sensor and FerroOrange staining. These observations were validated by applying LPAR3 siRNA in the experiments mentioned above. In addition, the protein expression level of nuclear factor erythroid 2-related factor (NRF2), a key regulator of oxidative stress, was also enhanced in OMPT-treated cells. Lastly, we verified that LPA3 plays a critical role in erastin-induced ferroptotic human erythroleukemia K562 cells. OMPT rescued the erythropoiesis defect caused by erastin in K562 cells based on a Gly A promoter luciferase assay. Taken together, our findings suggest that LPA3 activation inhibits cell ferroptosis by suppressing lipid oxidation and iron accumulation, indicating that ferroptosis could potentially serve as a link among LPA3, erythropoiesis, and aging.

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Section: Discussionmentioning

confidence: 93%

Lysophosphatidic Acid Receptor 3 Activation Is Involved in the Regulation of Ferroptosis

Huang,

Lin,

Chiang

et al. 2024

IJMS

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“…Resveratrol, identified as 3,4 Zhang et al, 2023). However, induction of ferroptosis by resveratrol in tumors seems to be promising as cancer cells are more dependent on iron.…”

Section: Resveratrolmentioning

confidence: 99%

Induction of ferroptosis by natural phenols: A promising strategy for cancer therapy

Zhang,

Xie

2024

Phytotherapy Research

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In recent years, heightened interest surrounds the exploration of natural phenols as potential agents for cancer therapy, specifically by inducing ferroptosis, a unique form of regulated cell death characterized by iron‐dependent lipid peroxidation. This review delves into the roles of key natural phenols, flavonoids, phenolic acids, curcumin, and stilbenes, in modulating ferroptosis and their underlying mechanisms. Emphasizing the significance of amino acid, lipid, and iron metabolism, the study elucidates the diverse pathways through which these phenols regulate ferroptosis. Notably, curcumin, a well‐known polyphenol, exhibits multifaceted interactions with cellular components involved in ferroptosis regulation, providing a distinctive therapeutic avenue. Stilbenes, another phenolic class, demonstrate promising potential in influencing lipid metabolism and iron‐dependent processes, contributing to ferroptotic cell death. Understanding the intricate interplay between these natural phenols and ferroptosis not only illuminates complex cellular regulatory networks but also unveils potential avenues for novel cancer therapies. Exploring these compounds as inducers of ferroptosis presents a promising strategy for targeted cancer treatment, capitalizing on the delicate balance between cellular metabolism and regulated cell death mechanisms. This article synthesizes current knowledge, aiming to stimulate further research into the therapeutic potential of natural phenols in the context of ferroptosis‐mediated cancer therapy.

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“…Since then, ferroptosis has drawn extensive attention in a variety of biomedical research fields, including anti-viral or anti-tumor immune responses, ischemic organ injury, as well as cancer (detailed review elsewhere [ 8 ]). Ferroptosis has also been demonstrated to play important physiological roles, such as erythroid maturation [ 9 ], platelet production [ 10 ], aging [ 11 ], and immune cell functions [ 12 , 13 , 14 ]. The number of publications related to ferroptosis has grown exponentially over the last decade [ 5 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular Mechanisms of Ferroptosis and Updates of Ferroptosis Studies in Cancers and Leukemia

Akiyama

Carter

Andreeff

et al. 2023

Cells

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Ferroptosis is a mode of cell death regulated by iron-dependent lipid peroxidation. Growing evidence suggests ferroptosis induction as a novel anti-cancer modality that could potentially overcome therapy resistance in cancers. The molecular mechanisms involved in the regulation of ferroptosis are complex and highly dependent on context. Therefore, a comprehensive understanding of its execution and protection machinery in each tumor type is necessary for the implementation of this unique cell death mode to target individual cancers. Since most of the current evidence for ferroptosis regulation mechanisms is based on solid cancer studies, the knowledge of ferroptosis with regard to leukemia is largely lacking. In this review, we summarize the current understanding of ferroptosis-regulating mechanisms with respect to the metabolism of phospholipids and iron as well as major anti-oxidative pathways that protect cells from ferroptosis. We also highlight the diverse impact of p53, a master regulator of cell death and cellular metabolic processes, on the regulation of ferroptosis. Lastly, we discuss recent ferroptosis studies in leukemia and provide a future perspective for the development of promising anti-leukemia therapies implementing ferroptosis induction.

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Inhibition of ferroptosis promotes megakaryocyte differentiation and platelet production

Cited by 7 publications

References 10 publications

Lysophosphatidic Acid Receptor 3 Activation Is Involved in the Regulation of Ferroptosis

Lysophosphatidic Acid Receptor 3 Activation Is Involved in the Regulation of Ferroptosis

Induction of ferroptosis by natural phenols: A promising strategy for cancer therapy

Molecular Mechanisms of Ferroptosis and Updates of Ferroptosis Studies in Cancers and Leukemia

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