scholarly journals Emerging Roles of 5-Lipoxygenase Phosphorylation in Inflammation and Cell Death

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Qian-Yi Sun ◽  
Hong-Hao Zhou ◽  
Xiao-Yuan Mao
Keyword(s):  
Lipid Peroxidation ◽  
Cell Death ◽  
Arachidonic Acid ◽  
Protein Phosphorylation ◽  
Redox State ◽  
Lipid Mediators ◽  
The Other ◽  
Rate Limiting ◽  
Iron And Calcium ◽  
Regulate Cell Death

5-Lipoxygenase (ALOX5) is an iron-containing and nonheme dioxygenase that catalyzes the peroxidation of polyunsaturated fatty acids such as arachidonic acid. ALOX5 is the rate-limiting enzyme for the biosynthesis of leukotrienes, a family of proinflammatory lipid mediators derived from arachidonic acid. ALOX5 also make great contributions to mediating lipid peroxidation. In recent years, it has been discovered that ALOX5 plays a central role in cell death including apoptosis, pyroptosis, and ferroptosis, a newly discovered type of cell death. According to the previous studies, ALOX5 can regulate cell death in two ways: one is inflammation and the other is lipid peroxidation. Meanwhile, it has been shown that ALOX5 activity is regulated by several factors including protein phosphorylation, ALOX5-interactng protein, redox state, and metal ions such as iron and calcium. In this review, we aim to summarize the knowledge on the emerging roles of ALOX5 protein phosphorylation in the regulation of cell death and inflammation in order to explore a potential target for human diseases.

Platelet Suruival and Function in Rats with Enhanced Thrombotic Tendency

1985 ◽  
Vol 54 (04) ◽  
pp. 739-743 ◽  
Author(s):  
Federica Delaini ◽  
Elisabetta Dejana ◽  
Ine Reyers ◽  
Elisa Vicenzi ◽  
Germana De Bellis Vitti ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Nephrotic Syndrome ◽  
Platelet Function ◽  
Laboratory Tests ◽  
Thrombus Formation ◽  
The Other ◽  
Mean Survival Time ◽  
The Mean ◽  
And Function ◽  
Thrombotic Tendency

SummaryWe have investigated the relevance of some laboratory tests of platelet function in predicting conditions of thrombotic tendency. For this purpose, we studied platelet survival, platelet aggregation in response to different stimuli, TxB2 and 6-keto-PGFlα production in serum of rats bearing a nephrotic syndrome induced by adriamycin. These animals show a heavy predisposition to the development of both arterial and venous thrombosis. The mean survival time was normal in nephrotic rats in comparison to controls. As to aggregation tests, a lower aggregating response was found in ADR-treated rats using ADP or collagen as stimulating agents. With arachidonic acid (AA) we observed similar aggregating responses at lower A A concentrations, whereas at higher AA concentrations a significantly lower response was found in nephrotic rats, despite their higher TxB2 production. Also TxB2 and 6-keto-PGFlα levels in serum of nephrotic rats were significantly higher than in controls. No consistent differences were found in PGI2-activity generated by vessels of control or nephrotic rats.These data show that platelet function may appear normal or even impaired in rats with a markedly increased thrombotic tendency. On the other hand, the significance of high TxB2 levels in connection with mechanisms leading to thrombus formation remains a controversial issue.

Thermodynamic and Kinetic Aspects of the Lipid Peroxidation of Arachidonic Acid

2011 ◽  
Vol 8 (4) ◽  
pp. 390-400
Author(s):  
Claire Claire E. Tornow ◽  
Betsy Lau ◽  
M. C. Milletti
Keyword(s):  
Lipid Peroxidation ◽  
Arachidonic Acid

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.

scholarly journals Kaempferol Ameliorates Oxygen-Glucose Deprivation/Reoxygenation-Induced Neuronal Ferroptosis by Activating Nrf2/SLC7A11/GPX4 Axis

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 923
Author(s):  
Yuan Yuan ◽  
Yanyu Zhai ◽  
Jingjiong Chen ◽  
Xiaofeng Xu ◽  
Hongmei Wang
Keyword(s):  
Lipid Peroxidation ◽  
Cell Death ◽  
Antioxidant Capacity ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation ◽  
Related Factor ◽  
Protective Effects

Kaempferol has been shown to protect cells against cerebral ischemia/reperfusion injury through inhibition of apoptosis. In the present study, we sought to investigate whether ferroptosis is involved in the oxygen-glucose deprivation/reperfusion (OGD/R)-induced neuronal injury and the effects of kaempferol on ferroptosis in OGD/R-treated neurons. Western blot, immunofluorescence, and transmission electron microscopy were used to analyze ferroptosis, whereas cell death was detected using lactate dehydrogenase (LDH) release. We found that OGD/R attenuated SLC7A11 and glutathione peroxidase 4 (GPX4) levels as well as decreased endogenous antioxidants including nicotinamide adenine dinucleotide phosphate (NADPH), glutathione (GSH), and superoxide dismutase (SOD) in neurons. Notably, OGD/R enhanced the accumulation of lipid peroxidation, leading to the induction of ferroptosis in neurons. However, kaempferol activated nuclear factor-E2-related factor 2 (Nrf2)/SLC7A11/GPX4 signaling, augmented antioxidant capacity, and suppressed the accumulation of lipid peroxidation in OGD/R-treated neurons. Furthermore, kaempferol significantly reversed OGD/R-induced ferroptosis. Nevertheless, inhibition of Nrf2 by ML385 blocked the protective effects of kaempferol on antioxidant capacity, lipid peroxidation, and ferroptosis in OGD/R-treated neurons. These results suggest that ferroptosis may be a significant cause of cell death associated with OGD/R. Kaempferol provides protection from OGD/R-induced ferroptosis partly by activating Nrf2/SLC7A11/GPX4 signaling pathway.

scholarly journals Lipid peroxidation and the subsequent cell death transmitting from ferroptotic cells to neighboring cells

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Hironari Nishizawa ◽  
Mitsuyo Matsumoto ◽  
Guan Chen ◽  
Yusho Ishii ◽  
Keisuke Tada ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Cell Death ◽  
Lipid Peroxide ◽  
Nih3t3 Cells ◽  
Regulated Cell Death ◽  
Primary Mouse ◽  
Ischemic Diseases ◽  
A Chain ◽  
Dying Cells

AbstractFerroptosis is a regulated cell death due to the iron-dependent accumulation of lipid peroxide. Ferroptosis is known to constitute the pathology of ischemic diseases, neurodegenerative diseases, and steatohepatitis and also works as a suppressing mechanism against cancer. However, how ferroptotic cells affect surrounding cells remains elusive. We herein report the transfer phenomenon of lipid peroxidation and cell death from ferroptotic cells to nearby cells that are not exposed to ferroptotic inducers (FINs). While primary mouse embryonic fibroblasts (MEFs) and NIH3T3 cells contained senescence-associated β-galactosidase (SA-β-gal)-positive cells, they were decreased upon induction of ferroptosis with FINs. The SA-β-gal decrease was inhibited by ferroptotic inhibitors and knockdown of Atg7, pointing to the involvement of lipid peroxidation and activated autophagosome formation during ferroptosis. A transfer of cell culture medium of cells treated with FINs, type 1 or 2, caused the reduction in SA-β-gal-positive cells in recipient cells that had not been exposed to FINs. Real-time imaging of Kusabira Orange-marked reporter MEFs cocultured with ferroptotic cells showed the generation of lipid peroxide and deaths of the reporter cells. These results indicate that lipid peroxidation and its aftereffects propagate from ferroptotic cells to surrounding cells, even when the surrounding cells are not exposed to FINs. Ferroptotic cells are not merely dying cells but also work as signal transmitters inducing a chain of further ferroptosis.

scholarly journals SET protein accumulation prevents cell death in head and neck squamous cell carcinoma through regulation of redox state and autophagy

2019 ◽  
Vol 1866 (4) ◽  
pp. 623-637 ◽  
Author(s):  
Amanda Tomie Ouchida ◽  
Valéria Tudella Uyemura ◽  
André Lima Queiroz ◽  
Verônica Soares Brauer ◽  
Marinaldo Pacífico Cavalcanti-Neto ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Death ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Redox State ◽  
Neck Squamous Cell Carcinoma ◽  
Protein Accumulation

scholarly journals Differential Mechanisms of Cell Death Induced by HDAC Inhibitor SAHA and MDM2 Inhibitor RG7388 in MCF-7 Cells

Cells ◽  
2018 ◽  
Vol 8 (1) ◽  
pp. 8 ◽  
Author(s):  
Umamaheswari Natarajan ◽  
Thiagarajan Venkatesan ◽  
Vijayaraghavan Radhakrishnan ◽  
Shila Samuel ◽  
Appu Rathinavelu
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Death ◽  
Cancer Cells ◽  
Hdac Inhibitor ◽  
The Other ◽  
Combination Treatments ◽  
Cycle Arrest ◽  
Anti Cancer ◽  
Mcf 7

Gene expression is often altered by epigenetic modifications that can significantly influence the growth ability and progression of cancers. SAHA (Suberoylanilide hydroxamic acid, also known as Vorinostat), a well-known Histone deacetylase (HDAC) inhibitor, can stop cancer growth and metastatic processes through epigenetic alterations. On the other hand, Letrozole is an aromatase inhibitor that can elicit strong anti-cancer effects on breast cancer through direct and indirect mechanisms. A newly developed inhibitor, RG7388 specific for an oncogene-derived protein called MDM2, is in clinical trials for the treatment of various cancers. In this paper, we performed assays to measure the effects of cell cycle arrest resulting from individual drug treatments or combination treatments with SAHA + letrozole and SAHA + RG7388, using the MCF-7 breast cancer cells. When SAHA was used individually, or in combination treatments with RG7388, a significant increase in the cytotoxic effect was obtained. Induction of cell cycle arrest by SAHA in cancer cells was evidenced by elevated p21 protein levels. In addition, SAHA treatment in MCF-7 cells showed significant up-regulation in phospho-RIP3 and MLKL levels. Our results confirmed that cell death caused by SAHA treatment was primarily through the induction of necroptosis. On the other hand, the RG7388 treatment was able to induce apoptosis by elevating BAX levels. It appears that, during combination treatments, with SAHA and RG7388, two parallel pathways might be induced simultaneously, that could lead to increased cancer cell death. SAHA appears to induce cell necroptosis in a p21-dependent manner, and RG7388 seems to induce apoptosis in a p21-independent manner, outlining differential mechanisms of cell death induction. However, further studies are needed to fully understand the intracellular mechanisms that are triggered by these two anti-cancer agents.

scholarly journals Cell Death in Coronavirus Infections: Uncovering Its Role during COVID-19

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1585
Author(s):  
Annamaria Paolini ◽  
Rebecca Borella ◽  
Sara De Biasi ◽  
Anita Neroni ◽  
Marco Mattioli ◽  
...  
Keyword(s):  
Cell Death ◽  
Immune Cells ◽  
Viral Infections ◽  
Virus Entry ◽  
Therapeutic Strategies ◽  
The Other ◽  
Cytokine Storm ◽  
Cytokines And Chemokines ◽  
Cell Death Mechanisms ◽  
The One

Cell death mechanisms are crucial to maintain an appropriate environment for the functionality of healthy cells. However, during viral infections, dysregulation of these processes can be present and can participate in the pathogenetic mechanisms of the disease. In this review, we describe some features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and some immunopathogenic mechanisms characterizing the present coronavirus disease (COVID-19). Lymphopenia and monocytopenia are important contributors to COVID-19 immunopathogenesis. The fine mechanisms underlying these phenomena are still unknown, and several hypotheses have been raised, some of which assign a role to cell death as far as the reduction of specific types of immune cells is concerned. Thus, we discuss three major pathways such as apoptosis, necroptosis, and pyroptosis, and suggest that all of them likely occur simultaneously in COVID-19 patients. We describe that SARS-CoV-2 can have both a direct and an indirect role in inducing cell death. Indeed, on the one hand, cell death can be caused by the virus entry into cells, on the other, the excessive concentration of cytokines and chemokines, a process that is known as a COVID-19-related cytokine storm, exerts deleterious effects on circulating immune cells. However, the overall knowledge of these mechanisms is still scarce and further studies are needed to delineate new therapeutic strategies.

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