Oxidative stress induces PKR-dependent apoptosis via IFN-γ activation signaling in Jurkat T cells

The flowers of French marigold (Tagetes patulaL.) are widely used in folk medicine, in particular for treating inflammation-related disorders. However, cellular mechanisms of this activity demand further investigation. In the present work, we studied the potential ofT. patulacompounds to alleviate the oxidative stress in hydrogen peroxide-challenged human lymphoblastoid Jurkat T-cells. Crude extracts of marigold flowers and purified fractions containing flavonoids patuletin, quercetagetin, and quercetin and their derivatives, as well as the carotenoid lutein, were brought in contact with Jurkat cells challenged with 25 or 50 μM H2O2. Hydrogen peroxide caused oxidative stress in the cells, manifested as generation of superoxide and peroxyl radicals, reduced viability, arrested cell cycle, and enhanced apoptosis. The stress was alleviated by marigold ingredients that demonstrated high radical-scavenging capacity and enhanced the activity of antioxidant enzymes involved in neutralization of reactive oxygen species. Flavonoid fraction rich in quercetin and quercetagetin showed the highest cytoprotective activity, while patuletin in high dose exerted a cytotoxic effect associated with its anticancer potential.T. patulacompounds enhanced the production of anti-inflammatory and antioxidant interleukin-10 (IL-10) in Jurkat cells. Both direct radical-scavenging capacity and stimulation of protective cellular mechanisms can underlay the anti-inflammatory properties of marigold flowers.

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Rosmarinic Acid-Rich Extracts of Summer Savory (Satureja hortensisL.) Protect Jurkat T Cells against Oxidative Stress

Oxidative Medicine and Cellular Longevity ◽

10.1155/2013/456253 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 21

Author(s):

Irakli Chkhikvishvili ◽

Tamar Sanikidze ◽

Nunu Gogia ◽

Tamar Mchedlishvili ◽

Maia Enukidze ◽

...

Keyword(s):

Oxidative Stress ◽

T Cells ◽

Rosmarinic Acid ◽

Jurkat Cells ◽

Peroxyl Radicals ◽

G1 Arrest ◽

Acid Fraction ◽

Cellular Mechanisms ◽

Jurkat T Cells ◽

Phenolic Fraction

Summer savory (Satureja hortensisL.,Lamiaceae) is used in several regions of the world as a spice and folk medicine. Anti-inflammatory and cytoprotective effects ofS. hortensisand of its rosmarinic acid-rich phenolic fraction have been demonstrated in animal trials. However, previous studies of rosmarinic acid in cell models have yielded controversial results. In this study, we investigated the effects of summer savory extracts on H2O2-challenged human lymphoblastoid Jurkat T cells. LC-MS analysis confirmed the presence of rosmarinic acid and flavonoids such as hesperidin and naringin in the phenolic fraction. Adding 25 or 50 µM of H2O2to the cell culture caused oxidative stress, manifested as generation of superoxide and peroxyl radicals, reduced cell viability, G0/G1 arrest, and enhanced apoptosis. This stress was significantly alleviated by the ethanolic and aqueous extracts ofS. hortensisand by the partially purified rosmarinic acid fraction. The application of an aqueousS. hortensisextract doubled the activity of catalase and superoxide dismutase in the cells. The production of IL-2 and IL-10 interleukins was stimulated by H2O2and was further enhanced by the addition of theS. hortensisextract or rosmarinic acid fraction. The H2O2-challenged Jurkat cells may serve as a model for investigating cellular mechanisms of cytoprotective phytonutrient effects.

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Vitamin E synthetic derivate—TPGS—selectively induces apoptosis in jurkat t cells via oxidative stress signaling pathways: implications for acute lymphoblastic leukemia

APOPTOSIS ◽

10.1007/s10495-016-1266-x ◽

2016 ◽

Vol 21 (9) ◽

pp. 1019-1032 ◽

Cited By ~ 15

Author(s):

Cristian Ruiz-Moreno ◽

Marlene Jimenez-Del-Rio ◽

Ligia Sierra-Garcia ◽

Betty Lopez-Osorio ◽

Carlos Velez-Pardo

Keyword(s):

Oxidative Stress ◽

T Cells ◽

Vitamin E ◽

Acute Lymphoblastic Leukemia ◽

Signaling Pathways ◽

Lymphoblastic Leukemia ◽

Stress Signaling ◽

Jurkat T Cells

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HIV-1 tat expression and sulphamethoxazole hydroxylamine mediated oxidative stress alter the disulfide proteome in Jurkat T cells

Virology Journal ◽

10.1186/s12985-018-0991-x ◽

2018 ◽

Vol 15 (1) ◽

Cited By ~ 2

Author(s):

Kemi Adeyanju ◽

John R. Bend ◽

Michael J. Rieder ◽

Gregory A. Dekaban

Keyword(s):

Oxidative Stress ◽

T Cells ◽

Jurkat T Cells ◽

Hiv 1

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Gamma Interferon Production by Hepatic NK T Cells during Escherichia coli Infection Is Resistant to the Inhibitory Effects of Oxidative Stress

Infection and Immunity ◽

10.1128/iai.71.5.2468-2477.2003 ◽

2003 ◽

Vol 71 (5) ◽

pp. 2468-2477 ◽

Cited By ~ 5

Author(s):

Guochi Zhang ◽

Robert Dru Nichols ◽

Masaru Taniguchi ◽

Toshinori Nakayama ◽

Michael J. Parmely

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Escherichia Coli ◽

T Cells ◽

Nk Cells ◽

Inhibitory Effects ◽

Gram Negative ◽

E Coli ◽

Nk T Cells ◽

Ifn Γ

ABSTRACT The reductive-oxidative status of tissues regulates the expression of many inflammatory genes that are induced during gram-negative bacterial infections. The cytokine gamma interferon (IFN-γ) is a potent stimulus for host inflammatory gene expression, and oxidative stress has been shown to inhibit its production in mice challenged with Escherichia coli bacteria. The objective of the present study was to characterize the cells that produced IFN-γ in a mouse bacterial peritonitis model and determine the effects of oxidative stress on their activation. The liver contained large numbers of IFN-γ-expressing lymphocytes following challenge with viable E. coli bacteria. The surface phenotypes of IFN-γ-expressing hepatic lymphocytes were those of natural killer (NK) cells (NK1.1+ CD3−), conventional T cells (NK1.1− CD3+), and NK T cells (NK1.1+ CD3+). Treating mice with diethyl maleate to deplete tissue thiols significantly impaired IFN-γ production by NK cells, conventional T cells, and CD1d-restricted NK T cells in response to E. coli challenge. However, IFN-γ expression by a subset of NK T cells, which did not bind α-galactosylceramide-CD1d tetramers, was resistant to the inhibitory effects of tissue oxidative stress. Stress-resistant IFN-γ-expressing cells were also predominantly CD8+ and bore γδ T-cell antigen receptors. The residual IFN-γ response by NK T cells may explain previous reports of hepatic gene expression following gram-negative bacterial challenge in thiol-depleted mice. The finding also demonstrates that innate immune cells differ significantly in their responses to altered tissue redox status.

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Cellular determinants involving mitochondrial dysfunction, oxidative stress and apoptosis correlate with the synergic cytotoxicity of epigallocatechin-3-gallate and menadione in human leukemia Jurkat T cells

Pharmacological Research ◽

10.1016/j.phrs.2015.12.013 ◽

2016 ◽

Vol 103 ◽

pp. 300-317 ◽

Cited By ~ 10

Author(s):

Ioana Teodora Tofolean ◽

Constanta Ganea ◽

Diana Ionescu ◽

Alexandru Filippi ◽

Alexandru Garaiman ◽

...

Keyword(s):

Oxidative Stress ◽

T Cells ◽

Mitochondrial Dysfunction ◽

Human Leukemia ◽

Jurkat T Cells

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CD4+ T lymphocytes mediate hypercholesterolemia-induced endothelial dysfunction via a NAD(P)H oxidase-dependent mechanism

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00989.2007 ◽

2008 ◽

Vol 294 (6) ◽

pp. H2619-H2626 ◽

Cited By ~ 3

Author(s):

Ryan M. Wolfort ◽

Karen Y. Stokes ◽

D. Neil Granger

Keyword(s):

Oxidative Stress ◽

T Cells ◽

Endothelial Cell ◽

T Lymphocytes ◽

Adoptive Transfer ◽

Cd4 T Cells ◽

Endothelial Cell Dysfunction ◽

Superoxide Generation ◽

Cell Dysfunction ◽

Ifn Γ

Although hypercholesterolemia is known to impair endothelium-dependent vasodilation (EDV) long before the appearance of atherosclerotic plaques, it remains unclear whether the immune mechanisms that have been implicated in atherogenesis also contribute to the early oxidative stress and endothelial cell dysfunction elicited by hypercholesterolemia. EDV (wire myography), superoxide generation (cytochrome c reduction), and NAD(P)H oxidase mRNA expression were monitored in aortic rings from wild-type (WT) and mutant mice placed on either a normal diet or a cholesterol-enriched diet (HC) for 2 wk. WT mice on HC exhibited impaired EDV, enhanced superoxide generation, and increased expression of NAD(P)H oxidase subunit Nox-2 mRNA. The impaired EDV and increased superoxide generation induced by HC were significantly blunted in severe combined immunodeficient (SCID) mice and CD4+ T lymphocyte-deficient mice. These responses were also attenuated in HC mice genetically deficient in IFN-γ; however, adoptive transfer of WT-HC CD4+ T lymphocytes to IFN-γ-deficient recipients restored HC-induced responses. The HC-induced impaired EDV and oxidative stress were also attenuated in HC mice genetically deficient in Nox-2 (gp91 phox−/−) and in WT→gp91 phox−/−-HC chimeras. HC-induced gp91 phox mRNA expression was significantly blunted in mice deficient in CD4+ T cells or IFN-γ and was restored with adoptive transfer of WT-HC CD4+ T cells to IFN-γ-deficient recipients. These findings implicate the immune system in the early endothelial cell dysfunction associated with hypercholesterolemia and are consistent with a mechanism of impaired EDV that is mediated by CD4+ T cells and IFN-γ, acting through the generation of superoxide from vascular NAD(P)H oxidase.

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