Ferroptosis

自噬是细胞内一种高度保守的生理过程，可通过溶酶体系统降解过量或受损的细胞器、有毒的蛋白聚集体和病原体等。最新研究表明，海马钙素样1（HPCAL1）可作为特异性自噬受体和铁死亡的正调节因子。HPCAL1可选择性降解钙粘素2（CDH2），加速脂质过氧化，促进癌细胞铁死亡。iHPCAL1是抑制HPCAL1的小分子化合物，可抑制Erastin诱导的肿瘤细胞铁死亡。此外，它还可以抑制铁死亡诱导的急性胰腺炎。本文通过对HPCAL1在铁死亡中的具体作用机制进行概述，为HPCAL1作为铁死亡相关疾病的潜在治疗靶点提供新思路和理论依据。
Ferroptosis ; Cell Line, Tumor ; Autophagy

Cardiovascular Diseases ; Ferroptosis ; Humans ; Reactive Oxygen Species

Ferroptosis, an iron-dependent form of regulated cell death driven by peroxidative damages of polyunsaturated-fatty-acid-containing phospholipids in cellular membranes, has recently been revealed to play an important role in radiotherapy-induced cell death and tumor suppression, and to mediate the synergy between radiotherapy and immunotherapy. In this review, we summarize known as well as putative mechanisms underlying the crosstalk between radiotherapy and ferroptosis, discuss the interactions between ferroptosis and other forms of regulated cell death induced by radiotherapy, and explore combination therapeutic strategies targeting ferroptosis in radiotherapy and immunotherapy. This review will provide important frameworks for future investigations of ferroptosis in cancer therapy.
Ferroptosis/immunology* ; Humans ; Immunotherapy ; Neoplasms/therapy* ; Radiotherapy

Ferroptosis is a new type of programmed cell death different from other cell death pathways such as apoptosis,autophagy,necrosis,and pyroptosis in terms of initiation,mechanisms,and molecular characteristics.As the accumulation of phospholipid hydroperoxides is the hallmark of ferroptosis,the balance between oxidative damage and antioxidant defense is critical to the regulatory mechanism of ferroptosis.In cancer,the upregulation of antioxidant defense pathways can inhibit ferroptosis,thereby promoting cancer cells to survive the oxidative stress and develop drug resistance.This review systematically introduces the main features and regulatory mechanisms of ferroptosis.In addition,we summarize the role of ferroptosis in the progression and drug resistance of malignant tumors,providing novel implications for further research on the pathogenesis of malignant tumors and discovery of new targets for anti-cancer therapy.
Humans ; Ferroptosis ; Antioxidants ; Apoptosis ; Neoplasms ; Autophagy

Ferroptosis ; Piperazines/pharmacology* ; Cell Line, Tumor

Humans ; Ferroptosis ; Leukemia, Myeloid, Acute/metabolism*

Recently, ferroptosis, an iron-dependent novel type of cell death, has been characterized as an excessive accumulation of lipid peroxides and reactive oxygen species. Emerging studies demonstrate that ferroptosis not only plays an important role in the pathogenesis and progression of chronic diseases, but also functions differently in the different disease context. Notably, it is shown that activation of ferroptosis could potently inhibit tumor growth and increase sensitivity to chemotherapy and immunotherapy in various cancer settings. As a result, the development of more efficacious ferroptosis agonists remains the mainstay of ferroptosis-targeting strategy for cancer therapeutics. By contrast, in non-cancerous chronic diseases, including cardiovascular & cerebrovascular diseases and neurodegenerative diseases, ferroptosis functions as a risk factor to promote these diseases progression through triggering or accelerating tissue injury. As a matter of fact, blocking ferroptosis has been demonstrated to effectively prevent ischemia-reperfusion heart disease in preclinical animal models. Therefore, it is a promising field to develope potent ferroptosis inhibitors for preventing and treating cardiovascular & cerebrovascular diseases and neurodegenerative diseases. In this article, we summarize the most recent progress on ferroptosis in chronic diseases, and draw attention to the possible clinical impact of this recently emerged ferroptosis modalities.
Animals ; Chronic Disease ; Ferroptosis ; physiology ; Iron ; metabolism ; Reactive Oxygen Species

OBJECTIVE: To explore the protective effect of vitamin E (VE) against radiation injury of hippocampal neurons in mice and explore the possible mechanism. METHODS: Cultured HT-22 and U251 cells with or without exposure to 8 Gy irradiation were treated with VE (200 μmol/L for 24 h), ferroptosis inhibitor (ferrostatin-1, 5 μmol/L for 24 h), apoptosis inhibitor (ZVAD-FMK, 2 μmol/L), or necroptosis inhibitor (100 μmol/L). MTT assay was used to evaluate the cell viability after the treatments, and reduced glutathione (GSH), malondialdehyde (MDA), lipid reactive oxygen species (lipid ROS), and intracellular iron ion levels were detected for assessment of ferroptosis. The mice exposed to 16 Gy irradiation with or without vitamin E (500 U/kg) treatment for 6 weeks were assessed for behavioral changes and cognitive functions using Morris water maze test. RESULTS: Treatment with VE significantly promoted the cell survival following irradiation in HT-22 cells ( < 0.05) but not in U251 cells ( > 0.05). Ferrostatin-1, but not ZVAD or the necroptosis inhibitor, promoted the survival of HT-22 cells following the irradiation. Exposure to irradiation significantly increased ferroptosis-related oxidative stress level in HT-22 cells, manifested by decreased GSH level and increased MDA, lipid ROS and intracellular iron ion levels ( < 0.05); treatment with VE and ferrostatin-1 both obviously reversed radiation-induced ferroptosis-related oxidative stress in the cells ( < 0.05). In Morris water maze test, the mice with radiation exposure showed obviously increased exploration time and distance ( < 0.05), which were significantly decreased after treatment with VE ( < 0.05). CONCLUSIONS Vitamin E reduces radiation injury by inhibiting ferroptosis in the hippocampal neurons in mice.
Animals ; Ferroptosis ; Hippocampus ; Mice ; Neurons ; Radiation Injuries ; Vitamin E

Apoptosis and autophagy of follicular granulosa cells play an important regulatory role in the process of ovarian follicular atresia in animals. Recent studies have shown that ferroptosis and pyroptosis are also involved in the process of ovarian follicular atresia. Ferroptosis is a form of cell death caused by iron-dependent lipid peroxidation and reactive oxygen species (ROS) accumulation. Studies have confirmed that autophagy- and apoptosis-mediated follicular atresia also have typical characteristics of ferroptosis. Pyroptosis is a pro-inflammatory cell death dependent on Gasdermin protein, which can regulate ovarian reproductive performance by regulating follicular granulosa cells. This article reviews the roles and mechanisms of several types of programmed cell death independently or interactively regulating follicular atresia, in order to expand the theoretical research on follicular atresia mechanism and provide the theoretical reference for the mechanism of programmed cell death-induced follicular atresia.
Female ; Animals ; Follicular Atresia ; Apoptosis ; Cell Death ; Ferroptosis ; Pyroptosis