scholarly journals Lysyl oxidase promotes neuronal ferroptosis exacerbating seizure-induced hippocampal damage

2019 ◽  
Author(s):  
Xiao-Yuan Mao ◽  
Ming-Zhu Jin ◽  
Qin Li ◽  
Ji-Ning Jia ◽  
Qian-Yi Sun ◽  
...  
Keyword(s):  
Cell Death ◽  
Lysyl Oxidase ◽  
Neuronal Loss ◽  
Hippocampal Damage ◽  
Oxygen Species ◽  
Murine Models ◽  
Ht22 Cells ◽  
Related Disease ◽  
Ros Accumulation ◽  
Dependent Cell

AbstractEpilepsy is a serious neurological disorder and characterized by recurrent and unprovoked seizures. A critical pathological factor in the seizure genesis is neuronal loss. However, mechanisms which lead to neuronal death remain elusive. Our present investigation depicted that ferroptosis, a recently discovered iron- and lipid peroxidation-dependent cell death, probably served as a mechanism in murine models of kainic acid (KA)-induced seizures. And treatment with ferroptosis inhibitors ferrostatin-1 (Fer-1), liproxstatin-1 (Lipo-1) or deferoxamine (DFO) significantly suppressed seizure severity and frequency. Using gene expression profiling in HT22 cells after glutamate exposure (a validated ferroptotic cell death model), we identified lysyl oxidase (Lox) as a novel inducer of ferroptosis. Mechanistically, Lox promoted ferroptosis via activation of extracellular regulated protein kinase (ERK)-dependent 5-lipoxygenase (Alox5) phosphorylation at serine 663 residue signaling, subsequent leading to lipid reactive oxygen species (ROS) accumulation. In a murine model of KA-induced seizure, we illustrated that administration of β-aminopropionitrile (BAPN), a specific Lox inhibitor, remarkably prevented seizure generation. Overall, these findings highlight Lox, a novel identified ferroptotic regulator in neurons, serves as a potential target for seizure-related disease including epilepsy.

scholarly journals Mitochondrion-Dependent Cell Death in TDP-43 Proteinopathies

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 376
Author(s):  
Chantal B. Lucini ◽  
Ralf J. Braun
Keyword(s):  
Cell Death ◽  
Oxygen Species ◽  
In Vivo Models ◽  
Dependent Cell ◽  
Cell Death Mechanisms ◽  
Sting Pathway ◽  
Mitochondrial Membrane Permeabilization

In the last decade, pieces of evidence for TDP-43-mediated mitochondrial dysfunction in neurodegenerative diseases have accumulated. In patient samples, in vitro and in vivo models have shown mitochondrial accumulation of TDP-43, concomitantly with hallmarks of mitochondrial destabilization, such as increased production of reactive oxygen species (ROS), reduced level of oxidative phosphorylation (OXPHOS), and mitochondrial membrane permeabilization. Incidences of TDP-43-dependent cell death, which depends on mitochondrial DNA (mtDNA) content, is increased upon ageing. However, the molecular pathways behind mitochondrion-dependent cell death in TDP-43 proteinopathies remained unclear. In this review, we discuss the role of TDP-43 in mitochondria, as well as in mitochondrion-dependent cell death. This review includes the recent discovery of the TDP-43-dependent activation of the innate immunity cyclic GMP-AMP synthase/stimulator of interferon genes (cGAS/STING) pathway. Unravelling cell death mechanisms upon TDP-43 accumulation in mitochondria may open up new opportunities in TDP-43 proteinopathy research.

scholarly journals Post-stress bacterial cell death mediated by reactive oxygen species

2019 ◽  
Vol 116 (20) ◽  
pp. 10064-10071 ◽  
Author(s):  
Yuzhi Hong ◽  
Jie Zeng ◽  
Xiuhong Wang ◽  
Karl Drlica ◽  
Xilin Zhao
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Bacterial Resistance ◽  
Reactive Oxygen ◽  
Temperature Sensitive ◽  
Oxygen Species ◽  
Stress Genes ◽  
Primary Stress ◽  
Bacterial Cell Death ◽  
Ros Accumulation

Antimicrobial efficacy, which is central to many aspects of medicine, is being rapidly eroded by bacterial resistance. Since new resistance can be induced by antimicrobial action, highly lethal agents that rapidly reduce bacterial burden during infection should help restrict the emergence of resistance. To improve lethal activity, recent work has focused on toxic reactive oxygen species (ROS) as part of the bactericidal activity of diverse antimicrobials. We report that whenEscherichia coliwas subjected to antimicrobial stress and the stressor was subsequently removed, both ROS accumulation and cell death continued to occur. Blocking ROS accumulation by exogenous mitigating agents slowed or inhibited poststressor death. Similar results were obtained with a temperature-sensitive mutational inhibition of DNA replication. Thus, bacteria exposed to lethal stressors may not die during treatment, as has long been thought; instead, death can occur after plating on drug-free agar due to poststress ROS-mediated toxicity. Examples are described in which (i) primary stress-mediated damage was insufficient to kill bacteria due to repair; (ii) ROS overcame repair (i.e., protection from anti-ROS agents was reduced by repair deficiencies); and (iii) killing was reduced by anti-oxidative stress genes acting before stress exposure. Enzymatic suppression of poststress ROS-mediated lethality by exogenous catalase supports a causal rather than a coincidental role for ROS in stress-mediated lethality, thereby countering challenges to ROS involvement in antimicrobial killing. We conclude that for a variety of stressors, lethal action derives, at least in part, from stimulation of a self-amplifying accumulation of ROS that overwhelms the repair of primary damage.

scholarly journals Ferroptosis in plants: triggers, proposed mechanisms, and the role of iron in modulating cell death

2020 ◽  
Author(s):  
Ayelén Mariana Distéfano ◽  
Gabriel Alejandro López ◽  
Nicolás Setzes ◽  
Fernanda Marchetti ◽  
Maximiliano Cainzos ◽  
...  
Keyword(s):  
Cell Death ◽  
Metabolic Pathways ◽  
Oxygen Species ◽  
Cell Death Pathway ◽  
Plant Life ◽  
Regulated Cell Death ◽  
Dependent Cell ◽  
Plant Life Cycle ◽  
High Degree

Abstract Regulated cell death plays key roles during essential processes throughout the plant life cycle. It takes part in specific developmental programs and maintains homeostasis of the organism in response to unfavorable environments. Ferroptosis is a recently discovered iron-dependent cell death pathway characterized by the accumulation of lipid reactive oxygen species. In plants, ferroptosis shares all the main hallmarks described in other systems. Those specific features include biochemical and morphological signatures that seem to be conserved among species. However, plant cells have specific metabolic pathways and a high degree of metabolic compartmentalization. Together with their particular morphology, these features add more complexity to the plant ferroptosis pathway. In this review, we summarize the most recent advances in elucidating the roles of ferroptosis in plants, focusing on specific triggers, the main players, and underlying pathways.

scholarly journals Dimethyl Sulfoxide Protects Escherichia coli from Rapid Antimicrobial-Mediated Killing

2016 ◽  
Vol 60 (8) ◽  
pp. 5054-5058 ◽  
Author(s):  
Hongfei Mi ◽  
Dai Wang ◽  
Yunxin Xue ◽  
Zhi Zhang ◽  
Jianjun Niu ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Reactive Oxygen Species ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Dimethyl Sulfoxide ◽  
Oxygen Species ◽  
Content Type ◽  
Antimicrobial Studies ◽  
Ros Accumulation ◽  
Short Time

ABSTRACTThe contribution of reactive oxygen species (ROS) to antimicrobial lethality was examined by treatingEscherichia coliwith dimethyl sulfoxide (DMSO), an antioxidant solvent frequently used in antimicrobial studies. DMSO inhibited killing by ampicillin, kanamycin, and two quinolones and had little effect on MICs. DMSO-mediated protection correlated with decreased ROS accumulation and provided evidence for ROS-mediated programmed cell death. These data support the contribution of ROS to antimicrobial lethality and suggest caution when using DMSO-dissolved antimicrobials for short-time killing assays.

Screening of lysyl oxidase (LOX) and lysyl oxidase like (LOXL) enzyme expression and activity in preterm prelabor rupture of fetal membranes

2015 ◽  
Vol 0 (0) ◽  
Author(s):  
Jossimara Polettini ◽  
Marcia G. Silva ◽  
Marian Kacerovsky ◽  
Tariq A. Syed ◽  
George R. Saade ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Lysyl Oxidase ◽  
Fetal Membranes ◽  
Oxygen Species ◽  
Enzyme Expression ◽  
Antioxidant Treatment ◽  
Related Disease ◽  
Prelabor Rupture Of Membranes ◽  
Expression And Activity

AbstractLysyl oxidase (LOX) and LOX like enzymes (LOXL1–4) physiologically remodel extracellular matrix and pathologically contribute to cellular senescence under oxidative stress (OS). We characterized LOX and LOXL expressions and activity in human fetal membranes.Human fetal membranes from women with uncomplicated pregnancies at term, preterm birth with intact membranes (PTB) or preterm prelabor rupture of membranes (pPROM), andIncrease of LOX expression in pPROM, an OS-related disease, and the apparent inhibition of LOX activity by CSE restored by antioxidant treatment suggest that reactive oxygen species might influence LOX-mediated tissue remodeling in fetal membranes. Balanced antioxidant supplementation during pregnancy may reduce the risk of pPROM by increasing LOX activity.

Fructose‐1,6‐bisphosphate induces generation of reactive oxygen species and activation of p53‐dependent cell death in human endometrial cancer cells

2020 ◽  
Author(s):  
Bruna Pasqualotto Costa ◽  
Marcella Tornquist Nassr ◽  
Fernando Mendonça Diz ◽  
Leonardo Pfeiff Carlessi ◽  
Krist Helen Antunes Fernandes ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Endometrial Cancer ◽  
Cancer Cells ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Dependent Cell ◽  
Fructose 1,6 Bisphosphate

scholarly journals Candida albicans infection disturbs the redox homeostasis system and induces reactive oxygen species accumulation for epithelial cell death

2019 ◽  
Vol 20 (4) ◽  
Author(s):  
Tongtong Ren ◽  
Hangqi Zhu ◽  
Lei Tian ◽  
Qilin Yu ◽  
Mingchun Li
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Candida Albicans ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Tissue Damage ◽  
Redox Homeostasis ◽  
Oxygen Species ◽  
Ros Accumulation ◽  
Epithelial Cell Death

ABSTRACT Candida albicans is a common pathogenic fungus with high mortality in immunocompromised patients. However, the mechanism by which C. albicans invades host epithelial cells and causes serious tissue damage remains to be further investigated. In this study, we established the C. albicans–293T renal epithelial cell interaction model to investigate the mechanism of epithelial infection by this pathogen. It was found that C. albicans infection causes severe cell death and reactive oxygen species (ROS) accumulation in epithelial cells. Further investigations revealed that C. albicans infection might up-regulate expression of nicotinamide adenine dinucleotide phosphate (NAPDH) oxidase (NOX), inhibit the activity of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), and suppress the p38–Nrf2–heme oxygenase-1 (HO-1) pathway which plays an important role in the elimination of intracellular ROS. Furthermore, epithelial cell death caused by the fungal infection could be strikingly alleviated by addition of the antioxidant agent glutathione, indicating the critical role of ROS accumulation in cell death caused by the fungus. This study revealed that disturbance of the redox homeostasis system and ROS accumulation in epithelial cells is involved in cell death caused by C. albicans infection, which sheds light on the application of antioxidants in the suppression of tissue damage caused by fungal infection.

scholarly journals Reactive oxygen species-provoked mitochondria-dependent cell death during ageing of elm (Ulmus pumilaL.) seeds

2015 ◽  
Vol 81 (3) ◽  
pp. 438-452 ◽  
Author(s):  
Yu Wang ◽  
Ying Li ◽  
Hua Xue ◽  
Hugh W. Pritchard ◽  
Xiaofeng Wang
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Dependent Cell
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