The production of reactive oxygen species enhanced with the reduction of menadione by active thioredoxin reductase

Li, Jing; Zuo, Xi‐Nian; Cheng, Ping; Ren, Xiaoyuan; Sun, Shibo; Xu, Jianqiang; Holmgren, Arne; Lu, Jun

doi:10.1039/c9mt00133f

Cited by 27 publications

(14 citation statements)

References 43 publications

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“…Our finding was consistent with a previous study that showed TXNRD1 was a target of miR-125b-5p [83]. TXNRD1 belongs to the pyrimidine nucleotide oxidoreductases family in the thioredoxin system and is a cytoplasmic antioxidant enzyme that regulates redox homeostasis [87,88]. Overexpression of TNXRD1 is associated with highly proliferative cells and high ROS levels, such as cancer cells, contributing to protecting cells from ROS [89].…”

Section: Discussionsupporting

confidence: 92%

PM10 Alters Trophoblast Cell Function and Modulates miR-125b-5p Expression

Chaiwangyen

Pintha

Tantipaiboonwong

et al. 2022

BioMed Research International

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Air pollution is one of the largest global environmental health hazards that threaten premature mortality or morbidity. Particulate matter 10 (PM10) has been demonstrated to contribute to several human diseases via dysregulated miRNA expression. Trophoblast cells play a key role in implantation and placentation for a successful pregnancy. Nonetheless, the PM10 associated trophoblast cell functions during pregnancy and miRNA expression are still unknown. Our study showed that PM10 affected HTR-8/SVneo cell viability and also decreased cell proliferation, migration, and invasion. A high concentration of PM10 caused an increase in HTR-8/SVneo cell apoptosis. Treatment with PM10 induced inflammation through the upregulated IL-1β, IL-6, and TNF-α expression in trophoblast cells. In PM10-treated HTR-8/SVneo cells, miR-125b-5p expression was considerably increased and TXNRD1 was found to be negatively related to miR-125b-5p. Collectively, our findings revealed that PM10 could alter miR-125b-5p expression by targeting TXNRD1 and suppressing trophoblast cell functions. Additional investigations relating to the function of miR-125b-5p and its target on particulate pollution exposure in trophoblast are warranted for future biomarker or effective therapeutic approaches.

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Section: Discussionsupporting

confidence: 92%

PM10 Alters Trophoblast Cell Function and Modulates miR-125b-5p Expression

Chaiwangyen

Pintha

Tantipaiboonwong

et al. 2022

BioMed Research International

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“…3c ), suggesting that other mechanisms (although less efficient) may contribute to the reduction of vitamin K. Indeed, menadione can be reduced non-enzymatically by glutathione (Extended Data Fig. 5c ), and enzymatically by NQO1 and/or thioredoxin reductase in addition to FSP1 28 , 29 . Thus, genetic deletion and pharmacological inhibition of FSP1 did not significantly influence the anti-ferroptotic effect of menadione, similar to other FSP1-independent ferroptosis inhibitors (Extended Data Fig.…”

Section: Vitamin K Blocks Ferroptosis Via Fsp1mentioning

confidence: 99%

A non-canonical vitamin K cycle is a potent ferroptosis suppressor

Mishima

Ito

et al. 2022

Nature

336

201

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Ferroptosis, a non-apoptotic form of cell death marked by iron-dependent lipid peroxidation1, has a key role in organ injury, degenerative disease and vulnerability of therapy-resistant cancers2. Although substantial progress has been made in understanding the molecular processes relevant to ferroptosis, additional cell-extrinsic and cell-intrinsic processes that determine cell sensitivity toward ferroptosis remain unknown. Here we show that the fully reduced forms of vitamin K—a group of naphthoquinones that includes menaquinone and phylloquinone3—confer a strong anti-ferroptotic function, in addition to the conventional function linked to blood clotting by acting as a cofactor for γ-glutamyl carboxylase. Ferroptosis suppressor protein 1 (FSP1), a NAD(P)H-ubiquinone reductase and the second mainstay of ferroptosis control after glutathione peroxidase-44,5, was found to efficiently reduce vitamin K to its hydroquinone, a potent radical-trapping antioxidant and inhibitor of (phospho)lipid peroxidation. The FSP1-mediated reduction of vitamin K was also responsible for the antidotal effect of vitamin K against warfarin poisoning. It follows that FSP1 is the enzyme mediating warfarin-resistant vitamin K reduction in the canonical vitamin K cycle6. The FSP1-dependent non-canonical vitamin K cycle can act to protect cells against detrimental lipid peroxidation and ferroptosis.

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“…[ 62 ] Endogenous antioxidants such as thioredoxin reductase‐1 even exaggerate the generation of ROS via redox cycling. [ 63 ] Intracellular H 2 O 2 can be produced via incomplete mitochondrial respiration, which could lead to mitochondrial membrane depolarization, lipid peroxidation, and DNA damage and induce beta‐cell apoptosis. [ 64–66 ]…”

Section: Discussionmentioning

confidence: 99%

Identification of Compounds Protecting Pancreatic Islets against Oxidative Stress using a 3D Pseudoislet Screening Platform

Rademakers,

Sthijns,

Paulino da Silva Filho

et al. 2023

Advanced Biology

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Oxidative stress leads to a lower success rate of clinical islet transplantation. Here, FDA‐approved compounds are screened for their potential to decrease oxidative stress and to protect or enhance pancreatic islet viability and function. Studies are performed on in vitro “pseudoislet” spheroids, which are pre‐incubated with 1280 different compounds and subjected to oxidative stress. Cell viability and oxidative stress levels are determined using a high‐throughput fluorescence microscopy pipeline. Initial screening on cell viability results in 59 candidates. The top ten candidates are subsequently screened for their potential to decrease induced oxidative stress, and eight compounds efficient reduction of induced oxidative stress in both alpha and beta cells by 2550%. After further characterization, the compound sulfisoxazole is found to be the most capable of reducing oxidative stress, also at short pre‐incubation times, which is validated in primary human islets, where low oxidative stress levels and islet function are maintained. This study shows an effective screening strategy with 3D cell aggregates based on cell viability and oxidative stress, which leads to the discovery of several compounds with antioxidant capacity. The top candidate, sulfisoxazole is effective after a 30 min pre‐incubation, maintains baseline islet function, and may help alleviate oxidative stress in pancreatic islets.

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The production of reactive oxygen species enhanced with the reduction of menadione by active thioredoxin reductase

Abstract: TXNRD1 participates in the ROS production with menadione by a one-electron reduction mechanism. TXNRD1 transfers electrons from NADPH to menadione to yield a semiquinone radical intermediate, which reacts with molecular oxygen to generate ROS.

Cited by 27 publications

References 43 publications

PM10 Alters Trophoblast Cell Function and Modulates miR-125b-5p Expression

PM10 Alters Trophoblast Cell Function and Modulates miR-125b-5p Expression

A non-canonical vitamin K cycle is a potent ferroptosis suppressor

Identification of Compounds Protecting Pancreatic Islets against Oxidative Stress using a 3D Pseudoislet Screening Platform

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