Promotion of HeLa cells apoptosis by cynaropicrin involving inhibition of thioredoxin reductase and induction of oxidative stress

Abstract Background Inflammation and oxidative stress form a vicious circle in atherosclerosis. Oxidative stress can have detrimental effects on T cells. A unique subset of CD4+ T cells, known as regulatory T (Treg) cells, has been associated with atheroprotective effects. Reduced numbers of Treg cells is a consistent finding in patients with chronic coronary syndrome (CCS). However, it is unclear to what extent these cells are sensitive to oxidative stress. In this pilot study, we tested the hypothesis that oxidative stress might be a potential contributor to the Treg cell deficit in CCS patients. Methods Thirty patients with CCS and 24 healthy controls were included. Treg (CD4+CD25+CD127−) and conventional T (CD4+CD25−, Tconv) cells were isolated and treated with increasing doses of H2O2. Intracellular ROS levels and cell death were measured after 2 and 18 h, respectively. The expression of antioxidant genes was measured in freshly isolated Treg and Tconv cells. Also, total antioxidant capacity (TAC) was measured in fresh peripheral blood mononuclear cells, and oxidized (ox) LDL/LDL ratios were determined in plasma. Results At all doses of H2O2, Treg cells accumulated more ROS and exhibited higher rates of death than their Tconv counterparts, p < 0.0001. Treg cells also expressed higher levels of antioxidant genes, including thioredoxin and thioredoxin reductase-1 (p < 0.0001), though without any differences between CCS patients and controls. Tconv cells from CCS patients were, on the other hand, more sensitive to oxidative stress ex vivo and expressed more thioredoxin reductase-1 than Tconv cells from controls, p < 0.05. Also, TAC levels were lower in patients, 0.97 vs 1.53 UAE/100 µg, p = 0.001, while oxLDL/LDL ratios were higher, 29 vs 22, p = 0.006. Conclusion Treg cells isolated from either CCS patients or healthy controls were all highly sensitive to oxidative stress ex vivo. There were signs of oxidant-antioxidant imbalance in CCS patients and we thus assume that oxidative stress may play a role in the reduction of Treg cells in vivo.

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Cytotoxicity induced by new spiral mesoporous silica nanorods via specific surface area and ROS accumulation in HeLa cells

Materials Advances ◽

10.1039/d0ma00199f ◽

2020 ◽

Vol 1 (9) ◽

pp. 3556-3564

Author(s):

Lan She ◽

Miao Sun ◽

Xinfang Li ◽

Anfeng Kang ◽

Feng Yang ◽

...

Keyword(s):

Oxidative Stress ◽

Mesoporous Silica ◽

Cell Viability ◽

Specific Surface ◽

Surface Area ◽

Specific Surface Area ◽

Hela Cells ◽

Ros Accumulation ◽

Silica Nanorods

Results indicated that the effect of MSNRs on cell viability and cellular oxidative stress was related to specific surface area.

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Role of thioredoxin reductase 1 in dysplastic transformation of human breast epithelial cells triggered by chronic oxidative stress

Scientific Reports ◽

10.1038/srep36860 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 19

Author(s):

Chaoran Dong ◽

Lei Zhang ◽

Ruoxuan Sun ◽

Jianying Liu ◽

Hanwei Yin ◽

...

Keyword(s):

Oxidative Stress ◽

Epithelial Cells ◽

Thioredoxin Reductase ◽

Human Breast ◽

Breast Epithelial Cells ◽

Chronic Oxidative Stress ◽

Thioredoxin Reductase 1 ◽

Breast Epithelial ◽

Human Breast Epithelial Cells

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Proteome-wide profiling of carbonylated proteins and carbonylation sites in HeLa cells under mild oxidative stress conditions

Free Radical Biology and Medicine ◽

10.1016/j.freeradbiomed.2013.11.030 ◽

2014 ◽

Vol 68 ◽

pp. 186-195 ◽

Cited By ~ 37

Author(s):

Ravi Chand Bollineni ◽

Ralf Hoffmann ◽

Maria Fedorova

Keyword(s):

Oxidative Stress ◽

Hela Cells ◽

Stress Conditions

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Oxidative Stress Response in Regulatory and Conventional T Cells: A Comparison Between Patients with Chronic Coronary Syndrome and Healthy Subjects

10.21203/rs.3.rs-110580/v1 ◽

2020 ◽

Author(s):

Anna K Lundberg ◽

Rosanna WS Chung ◽

Louise Zeijlon ◽

Gustav Fernström ◽

Lena Jonasson

Keyword(s):

Oxidative Stress ◽

T Cells ◽

Mononuclear Cells ◽

Ex Vivo ◽

Thioredoxin Reductase ◽

Healthy Controls ◽

Antioxidant Genes ◽

Consistent Finding ◽

Coronary Syndrome ◽

Thioredoxin Reductase 1

Abstract BackgroundInflammation and oxidative stress form a vicious circle in atherosclerosis. Oxidative stress can have detrimental effects on T cells. A unique subset of CD4+ T cells, known as regulatory T (Treg) cells, has been associated with atheroprotective effects. Reduced numbers of Treg cells is a consistent finding in patients with chronic coronary syndrome (CCS). However, it is unclear to what extent these cells are sensitive to oxidative stress. In the present study, we tested the hypothesis that oxidative stress might be a potential contributor to the Treg cell deficit in CCS patients. MethodsThirty patients with CCS and 24 healthy controls were included. Treg (CD4+CD25+CD127-) and conventional T (CD4+CD25-, Tconv) cells were isolated and treated with increasing doses of H2O2. Intracellular ROS levels and cell death were measured after 2 and 18 h, respectively. The expression of antioxidant genes was measured in freshly isolated Treg and Tconv cells. Alxo, total antioxidant capacity (TAC) was measured in fresh peripheral blood mononuclear cells. ResultsAt all doses of H2O2, Treg cells accumulated more ROS and exhibited higher rates of death than their Tconv counterparts, p < 0.0001. Treg cells also expressed higher levels of antioxidant genes, including thioredoxin and thioredoxin reductase-1 (p < 0.0001), though without any differences between CCS patients and controls. Tconv cells from CCS patients were, on the other hand, more sensitive to oxidative stress ex vivo and expressed more thioredoxin reductase-1 than Tconv cells from controls, p < 0.05. Also, TAC levels were lower in patients, 0.97 vs 1.53 UAE/100 µg, p = 0.001. ConclusionTreg cells isolated from either CCS patients or healthy controls were all highly sensitive to oxidative stress ex vivo. There were however signs of oxidant-antioxidant imbalance in CCS patients and we thus assume that oxidative stress plays a role in the reduction of Treg cells in vivo.

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Acetylated Thioredoxin Reductase 1 Resists Oxidative Inactivation

Frontiers in Chemistry ◽

10.3389/fchem.2021.747236 ◽

2021 ◽

Vol 9 ◽

Author(s):

David. E. Wright ◽

Nikolaus Panaseiko ◽

Patrick O’Donoghue

Keyword(s):

Oxidative Stress ◽

Thioredoxin Reductase ◽

Oxygen Species ◽

Site Specific ◽

Oxidative Inactivation ◽

Thioredoxin Reductase 1 ◽

Lysine Residues ◽

Canonical Amino Acid ◽

Genetic Code Expansion ◽

Low Activity

Thioredoxin Reductase 1 (TrxR1) is an enzyme that protects human cells against reactive oxygen species generated during oxidative stress or in response to chemotherapies. Acetylation of TrxR1 is associated with oxidative stress, but the function of TrxR1 acetylation in oxidizing conditions is unknown. Using genetic code expansion, we produced recombinant and site-specifically acetylated variants of TrxR1 that also contain the non-canonical amino acid, selenocysteine, which is essential for TrxR1 activity. We previously showed site-specific acetylation at three different lysine residues increases TrxR1 activity by reducing the levels of linked dimers and low activity TrxR1 tetramers. Here we use enzymological studies to show that acetylated TrxR1 is resistant to both oxidative inactivation and peroxide-induced multimer formation. To compare the effect of programmed acetylation at specific lysine residues to non-specific acetylation, we produced acetylated TrxR1 using aspirin as a model non-enzymatic acetyl donor. Mass spectrometry confirmed aspirin-induced acetylation at multiple lysine residues in TrxR1. In contrast to unmodified TrxR1, the non-specifically acetylated enzyme showed no loss of activity under increasing and strongly oxidating conditions. Our data suggest that both site-specific and general acetylation of TrxR1 regulate the enzyme’s ability to resist oxidative damage.

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Inhibition of Glutathione and Thioredoxin Metabolism Enhances Sensitivity to Perifosine in Head and Neck Cancer Cells

Journal of Oncology ◽

10.1155/2009/519563 ◽

2009 ◽

Vol 2009 ◽

pp. 1-10 ◽

Cited By ~ 25

Author(s):

Andrean L. Simons ◽

Arlene D. Parsons ◽

Katherine A. Foster ◽

Kevin P. Orcutt ◽

Melissa A. Fath ◽

...

Keyword(s):

Oxidative Stress ◽

Head And Neck Cancer ◽

Head And Neck ◽

Neck Cancer ◽

Reductase Activity ◽

Thioredoxin Reductase ◽

Buthionine Sulfoximine ◽

Human Head ◽

Akt Inhibitor ◽

Simultaneous Treatment

The hypothesis that the Akt inhibitor, perifosine (PER), combined with inhibitors of glutathione (GSH) and thioredoxin (Trx) metabolism will induce cytotoxicity via metabolic oxidative stress in human head and neck cancer (HNSCC) cells was tested. PER induced increases in glutathione disulfide (%GSSG) in FaDu, Cal-27, and SCC-25 HNSCCs as well as causing significant clonogenic cell killing in FaDu and Cal-27, which was suppressed by simultaneous treatment with N-acetylcysteine (NAC). An inhibitor of GSH synthesis, buthionine sulfoximine (BSO), sensitized Cal-27 and SCC-25 cells to PER-induced clonogenic killing as well as decreased total GSH and increased %GSSG. Additionally, inhibition of thioredoxin reductase activity (TrxRed) with auranofin (AUR) was able to induce PER sensitization in SCC-25 cells that were initially refractory to PER. These results support the conclusion that PER induces oxidative stress and clonogenic killing in HNSCC cells that is enhanced with inhibitors of GSH and Trx metabolism.

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