Cystine/glutamate transporter, system x c − , is involved in nitric oxide production in mouse peritoneal macrophages

Kobayashi, Sho; Hamashima, Shinji; Homma, Takujiro; Sato, Mami; Kusumi, Ryosuke; Bannai, Shiro; Fujii, Junichi; Sato, Hiroki

doi:10.1016/j.niox.2018.05.005

Cited by 22 publications

(9 citation statements)

References 35 publications

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“…The xCT inhibitor SSZ prevented the increase in Cys levels and suppressed the surge of P-SSH formation in M1-stimulated cells. These observations extend several reports on metabolic changes that occur in LPS-stimulated monocytes/macrophage, documenting the upregulation of intracellular levels of Cys and related metabolites [ [63] , [64] , [65] , [66] ]. Our data suggest that cellular uptake of cystine is crucial for driving protein persulfidation in activated human and mouse macrophages.…”

Section: Discussionsupporting

confidence: 88%

“…Our data suggest that cellular uptake of cystine is crucial for driving protein persulfidation in activated human and mouse macrophages. Inhibition of xCT indeed most profoundly suppressed persulfidation, adding to growing evidence for the importance of cystine import in macrophage activation [ 65 , 66 ]. Persulfidation was also sensitive to inhibition of CSE, whereas inhibition of CBS and MPST had only a minor effect.…”

Section: Discussionmentioning

confidence: 99%

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Widespread S-persulfidation in activated macrophages as a protective mechanism against oxidative-inflammatory stress

Salti,

Braunstein,

Haimovich

et al. 2024

Redox Biology

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Widespread S-persulfidation in activated macrophages as a protective mechanism against oxidative-inflammatory stress

Salti,

Braunstein,

Haimovich

et al. 2024

Redox Biology

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“…NO is an important regulating mediator in cells, which is not only an antimicrobial, tumoricidal, and tissue-damaging effector molecule working in the innate immune system but also an effective molecule for the adaptive immune response and cytoprotection [ 29 ]. NO is synthesized by nitric oxide synthase (NOS) from nicotinamide adenine dinucleotide phosphate, L-arginine, and oxygen.…”

Section: Discussionmentioning

confidence: 99%

The effect ofPanax notoginsengsaponins on oxidative stress induced by PCV2 infection in immune cells:in vitroandin vivostudies

Wang

Kuang

et al. 2020

J Vet Sci

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Background: Panax notoginseng saponins (PNS) are bioactive substances extracted from P. notoginseng that are widely used to treat cardiovascular and cerebrovascular diseases and interstitial diseases. PNS have the functions of scavenging free radicals, anti-inflammation, improving blood supply for tissue and so on. Objectives: The aim of this study was to investigate the effects of PNS on the oxidative stress of immune cells induced by porcine circovirus 2 (PCV2) infection in vitro and in vivo. Methods: Using an oxidative stress model of PCV2 infection in a porcine lung cell line (3D4/2 cells) and mice, the levels of nitric oxide (NO), reactive oxygen species (ROS), total glutathione (T-GSH), reduced glutathione (GSH), and oxidized glutathione (GSSG) and the activities of xanthine oxidase (XOD), myeloperoxidase (MPO) and inducible nitric oxide synthetase (iNOS) were determined to evaluate the regulatory effects of PNS on oxidative stress. Results: PNS treatment significantly reduced the levels of NO and ROS, the content of GSSG and the activities of XOD, MPO, and iNOS (p < 0.05), while significantly increasing GSH and the ratio of GSH/GSSG in infected 3D4/2 cells (p < 0.05).Similarly, in the in vivo study, PNS treatment significantly decreased the level of ROS in spleen lymphocytes of infected mice (p < 0.05), increased the levels of GSH and T-GSH (p < 0.05), significantly decreased the GSSG level (p < 0.05), and decreased the activities of XOD, MPO, and iNOS. Conclusions: PNS could regulate the oxidative stress of immune cells induced by PCV2 infection in vitro and in vivo.

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“…The presence of excessive levels of RNOS may cause uncoupling between these two domains and produce O 2 • − from NOS2, which aggravates organ damage, as is presumed for cardiovascular dysfunction under sepsis [ 115 ]. Macrophages themselves are relatively resistant to these oxidizing molecules ROS/RNOS and ferroptotic death under a xCT deficiency [ 116 , 117 ]. The proliferation of microbes requires iron as an essential nutrient.…”

Section: Metabolic Remodeling and Autoregulation Of M1-polarized Macr...mentioning

confidence: 99%

Involvement of Nitric Oxide in Protecting against Radical Species and Autoregulation of M1-Polarized Macrophages through Metabolic Remodeling

Fujii

Osaki

2023

Molecules

Self Cite

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When the expression of NOS2 in M1-polarized macrophages is induced, huge amounts of nitric oxide (•NO) are produced from arginine and molecular oxygen as the substrates. While anti-microbial action is the primary function of M1 macrophages, excessive activation may result in inflammation being aggravated. The reaction of •NO with superoxide produces peroxynitrite, which is highly toxic to cells. Alternatively, however, this reaction eliminates radial electrons and may occasionally alleviate subsequent radical-mediated damage. Reactions of •NO with lipid radicals terminates the radical chain reaction in lipid peroxidation, which leads to the suppression of ferroptosis. •NO is involved in the metabolic remodeling of M1 macrophages. Enzymes in the tricarboxylic acid (TCA) cycle, notably aconitase 2, as well as respiratory chain enzymes, are preferential targets of •NO derivatives. Ornithine, an alternate compound produced from arginine instead of citrulline and •NO, is recruited to synthesize polyamines. Itaconate, which is produced from the remodeled TCA cycle, and polyamines function as defense systems against overresponses of M1 macrophages in a feedback manner. Herein, we overview the protective aspects of •NO against radical species and the autoregulatory systems that are enabled by metabolic remodeling in M9-polarized macrophages.

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Cystine/glutamate transporter, system x c − , is involved in nitric oxide production in mouse peritoneal macrophages

Cited by 22 publications

References 35 publications

Widespread S-persulfidation in activated macrophages as a protective mechanism against oxidative-inflammatory stress

Widespread S-persulfidation in activated macrophages as a protective mechanism against oxidative-inflammatory stress

The effect ofPanax notoginsengsaponins on oxidative stress induced by PCV2 infection in immune cells:in vitroandin vivostudies

Involvement of Nitric Oxide in Protecting against Radical Species and Autoregulation of M1-Polarized Macrophages through Metabolic Remodeling

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