scholarly journals Ferroptosis: the potential value target in atherosclerosis

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Siyu Ouyang ◽  
Jia You ◽  
Chenxi Zhi ◽  
Pin Li ◽  
Xiaoyan Lin ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Cell Death ◽  
Theoretical Basis ◽  
Vascular Endothelial Cells ◽  
Necrotic Core ◽  
Vascular Endothelial ◽  
Intracellular Iron ◽  
Future Studies ◽  
Dependent Form ◽  
Pathologic Processes

AbstractIn advanced atherosclerosis (AS), defective function-induced cell death leads to the formation of the characteristic necrotic core and vulnerable plaque. The forms and mechanisms of cell death in AS have recently been elucidated. Among them, ferroptosis, an iron-dependent form of necrosis that is characterized by oxidative damage to phospholipids, promotes AS by accelerating endothelial dysfunction in lipid peroxidation. Moreover, disordered intracellular iron causes damage to macrophages, vascular smooth muscle cells (VSMCs), vascular endothelial cells (VECs), and affects many risk factors or pathologic processes of AS such as disturbances in lipid peroxidation, oxidative stress, inflammation, and dyslipidemia. However, the mechanisms through which ferroptosis initiates the development and progression of AS have not been established. This review explains the possible correlations between AS and ferroptosis, and provides a reliable theoretical basis for future studies on its mechanism.

scholarly journals ATF3 contributes to brucine-triggered glioma cell ferroptosis via promotion of hydrogen peroxide and iron

2021 ◽  
Author(s):  
Shan Lu ◽  
Xuan-zhong Wang ◽  
Chuan He ◽  
Lei Wang ◽  
Shi-peng Liang ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Cell Death ◽  
Er Stress ◽  
Glioma Cell ◽  
Nuclear Translocation ◽  
Indole Alkaloid ◽  
Ammonium Citrate ◽  
Ferric Ammonium Citrate ◽  
Activating Transcription Factor 3 ◽  
Intracellular Iron

AbstractFerroptotic cell death is characterized by iron-dependent lipid peroxidation that is initiated by ferrous iron and H2O2 via Fenton reaction, in which the role of activating transcription factor 3 (ATF3) remains elusive. Brucine is a weak alkaline indole alkaloid extracted from the seeds of Strychnos nux-vomica, which has shown potent antitumor activity against various tumors, including glioma. In this study, we showed that brucine inhibited glioma cell growth in vitro and in vivo, which was paralleled by nuclear translocation of ATF3, lipid peroxidation, and increases of iron and H2O2. Furthermore, brucine-induced lipid peroxidation was inhibited or exacerbated when intracellular iron was chelated by deferoxamine (500 μM) or improved by ferric ammonium citrate (500 μM). Suppression of lipid peroxidation with lipophilic antioxidants ferrostatin-1 (50 μM) or liproxstatin-1 (30 μM) rescued brucine-induced glioma cell death. Moreover, knockdown of ATF3 prevented brucine-induced accumulation of iron and H2O2 and glioma cell death. We revealed that brucine induced ATF3 upregulation and translocation into nuclei via activation of ER stress. ATF3 promoted brucine-induced H2O2 accumulation via upregulating NOX4 and SOD1 to generate H2O2 on one hand, and downregulating catalase and xCT to prevent H2O2 degradation on the other hand. H2O2 then contributed to brucine-triggered iron increase and transferrin receptor upregulation, as well as lipid peroxidation. This was further verified by treating glioma cells with exogenous H2O2 alone. Moreover, H2O2 reversely exacerbated brucine-induced ER stress. Taken together, ATF3 contributes to brucine-induced glioma cell ferroptosis via increasing H2O2 and iron.

Trans, trans-2,4-decadienal Induces Endothelial Cells Injury by Impairing Mitochondrial Function and Suppressing Autophagy

2021 ◽  
Author(s):  
Yuanyuan Hu ◽  
Guanhua Zhao ◽  
Lei Qin ◽  
Zhenlong Yu ◽  
Min Zhang ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Endothelial Cells ◽  
Mitochondrial Function ◽  
Crucial Role ◽  
Cardiovascular Health ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial

Trans, trans-2,4-decadienal (tt-DDE), one of the major lipid peroxidation-derived aldehydes, has unique reactivity that is potentially toxic to human. Vascular endothelial cells play a crucial role in maintaining cardiovascular health....

Induction of Apoptotic Cell Death in Vascular Endothelial Cells Cultured in Three-Dimensional Collagen Lattice

1999 ◽  
Vol 248 (2) ◽  
pp. 498-508 ◽  
Author(s):  
Masafumi Kuzuya ◽  
Shosuke Satake ◽  
Miguel A. Ramos ◽  
Shigeru Kanda ◽  
Teruhiko Koike ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Death ◽  
Vascular Endothelial Cells ◽  
Apoptotic Cell ◽  
Three Dimensional ◽  
Apoptotic Cell Death ◽  
Vascular Endothelial ◽  
Collagen Lattice ◽  
Cells Cultured

scholarly journals SUN-211 Active Steroid Hormone Synthesis Renders Adrenocortical Cells Highly Susceptible to Type II Ferroptosis Induction

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Isabel Weigand ◽  
Jochen Schreiner ◽  
Florian Roehrig ◽  
Na Sun ◽  
Landwehr Laura-Sophie ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Cell Death ◽  
Treatment Options ◽  
Cortical Cell ◽  
Current Treatment ◽  
Adrenocortical Cells ◽  
Hormone Synthesis ◽  
Steroidogenic Cell ◽  
Coa Ligase ◽  
Dependent Form

Abstract Context: Cell death in the adrenal cortex is ill understood but of high clinical relevance. Resistance of adrenocortical carcinoma (ACC) to current treatment with mitotane and chemotherapy calls for an improved understanding of adrenal cortical cell death processes. Ferroptosis is an iron-dependent form of regulated cell death which is characterized by polyunsaturated lipids adrenic (AdA) and arachidonic acid (AA) peroxidation. Aim: To address the potential role of ferroptosis in the adrenal gland as a potential treatment target of ACC. Methods: Human ACC cells H295R, CU-ACC1 and 2 were used. Protein expression of key enzymes was determined by western blotting. Lipid peroxidation was quantified with BODIPY 581/591 and cell viability with CellTiterGlo after treatment with known inducers and inhibitors of ferroptosis and steroidogenesis, respectively. Results: Adrenocortical tissues are enriched in AdA and AA and express high levels of genes relevant to ferroptosis, such as glutathione peroxidase 4 (GPX4) and long-chain-fatty-acid CoA ligase 4 (ACSL4). Inhibition of GPX4 with RSL3 led to cell death in H295R, CU-ACC1 and 2 cells at EC50 values of 2.4x10-7, 8.1x10-7 and 1.5x10-8 M, respectively. The steroidogenesis inhibitor ketoconazole completely reversed RSL3 cytotoxicity in all three steroidogenic cell lines by reducing lipid peroxidation. Mitotane induced lipid peroxidation but inhibition of ferroptosis with liproxstatin did not protect mitotane-induced cell death. Conclusion: Adrenocortical cells are highly sensitive to ferroptosis due to active steroidogenesis. Triggering this form of cell death could present future novel treatment options against ACC.

Antiprogrammed cell death protein 1 immunotherapy for angiosarcoma with high programmed death-ligand 1 expression: a case report

Immunotherapy ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 771-776
Author(s):  
Fei Xu ◽  
Jing Zheng ◽  
Mengjiao Fu ◽  
Hua Zhou
Keyword(s):  
Cell Death ◽  
Vascular Endothelial Cells ◽  
Single Case ◽  
Vascular Endothelial ◽  
Prediction Of Response ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Cancer Types ◽  
Rare Malignancy ◽  
Cell Death Protein

Background: Angiosarcoma (AS) is a rare malignancy originating from lymphatic or vascular endothelial cells. Prognosis of the disease is usually dismal and there is no effective treatment. Immunotherapy has been proved to be effective for various cancer types. Programmed death-ligand 1 (PD-L1) expression is generally recognized as a biomarker for the prediction of response to anti-PD-(L)1 immunotherapies. Methods & results: Here, we discuss a single case by highlighting the treatment of the antiprogrammed cell death protein 1 drug pembrolizumab with high PD-L1 expression. CT scan demonstrated a confirmed size reduction of some lesions compared with original lesions, which indicates the possible clinical benefit. Conclusion: We speculate that early anti-PD-1 treatment may be a promising strategy for angiosarcoma patients with high PD-L1 expression.

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