Citrullination of actin-ligand and nuclear structural proteins, cytoskeleton reorganization and protein redistribution across cellular fractions are early events in ionomycin-induced NETosis

Reis, Lorenna Rocha; Souza, Douglas Ricardo de; Tomasin, Rebeka; Bruni‐Cardoso, Alexandre; Mascio, Paolo Di; Ronsein, Graziella Eliza

doi:10.1016/j.redox.2023.102784

Cited by 7 publications

(3 citation statements)

References 85 publications

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“…NETosis assay was conducted on human neutrophils adhered to lysine-coated glass coverslips as previously reported. 80 After neutrophils’ adhesion, the compounds were diluted in RPMI medium (free of phenol red and fetal bovine serum) at a final concentration of 20 μM (0.15% DMSO) and added to the cells for 15 min at 37 °C in a 5% CO 2 atmosphere. Then, MSU crystals (250 μg/mL), known to induce NETosis, were added.…”

Section: Methodsmentioning

confidence: 99%

Targeting Myeloperoxidase Ameliorates Gouty Arthritis: A Virtual Screening Success Story

Matos,

Dallazen,

Reis

et al. 2024

J. Med. Chem.

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This study presents a new approach for identifying myeloperoxidase (MPO) inhibitors with strong in vivo efficacy. By combining inhibitor-like rules and structure-based virtual screening, the pipeline achieved a 70% success rate in discovering diverse, nanomolarpotency reversible inhibitors and hypochlorous acid (HOCl) scavengers. Mechanistic analysis identified RL6 as a genuine MPO inhibitor and RL7 as a potent HOCl scavenger. Both compounds effectively suppressed HOCl production in cells and neutrophils, with RL6 showing a superior inhibition of neutrophil extracellular trap release (NETosis). In a gout arthritis mouse model, intraperitoneal RL6 administration reduced edema, peroxidase activity, and IL-1β levels. RL6 also exhibited oral bioavailability, significantly reducing paw edema when administered orally. This study highlights the efficacy of integrating diverse screening methods to enhance virtual screening success, validating the anti-inflammatory potential of potent inhibitors, and advancing the MPO inhibitor research.

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Section: Methodsmentioning

confidence: 99%

Targeting Myeloperoxidase Ameliorates Gouty Arthritis: A Virtual Screening Success Story

Matos,

Dallazen,

Reis

et al. 2024

J. Med. Chem.

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“…72 LC−MS/MS Measurements for Proteomics. The peptides were separated and analyzed in a Nano EASY-nLC 1200 (Thermo Fisher Scientific, Bremen, Germany) coupled to an Orbitrap Fusion Lumos mass spectrometer (Thermo Fisher Scientific, Bremen, Germany) as described before, 73 with some modifications. Each sample (200 ng) was injected into a trap column (nano Viper C18, 3 μm, 75 μm × 2 cm, Thermo Scientific) with 20 μL of solvent A (0.1% formic acid) at 500 bar.…”

Section: Chemical Research In Toxicologymentioning

confidence: 99%

Nicotinamide riboside Induced Energy Stress and Metabolic Reprogramming in BEAS-2B Cells

Cordeiro,

Marzola,

Maekawa

et al. 2024

Chem. Res. Toxicol.

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Nicotinamide riboside (NR), a NAD + precursor, has received attention due to several health benefits it has induced in experimental models. Studies in cultured cells, animals, and humans consistently show increased NAD + availability after NR supplementation, which is considered the only mode of NR action that leads to health benefits. In the present study, we show that a persistently low NR concentration (1 μM) in the growth medium of BEAS-2B human cells, grown in a monolayer, induces energy stress, which precedes a cellular NAD + increase after 192 h. NR concentrations greater than 1 μM under the specified conditions were cytotoxic in the 2D cell culture model, while all concentrations tested in the 3D cell culture model (BEAS-2B cell spheroids exposed to 1, 5, 10, and 50 μM NR) induced apoptosis. Shotgun proteomics revealed that NR modulated the abundance of proteins, agreeing with the observed effects on cellular energy metabolism and cell growth or survival. Energy stress may activate pathways that lead to health benefits such as cancer prevention. Accordingly, the premalignant 1198 cell line was more sensitive to NR cytotoxicity than the phenotypically normal parent BEAS-2B cell line. The role of a mild energy stress induced by low concentrations of NR in its beneficial effects deserves further investigation. On the other hand, strategies to increase the bioavailability of NR require attention to toxic effects that may arise.

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“…13,14 PAD4 and cell cycle proteins jointly regulate nuclear membrane rupture, 15 and actin leads to plasma membrane rupture. 16,17 Finally, with fragmentation of the cell membrane, the decondensed chromatin is mixed with granule proteins, which are released into the extracellular space to form NETs.…”

Section: Introductionmentioning

confidence: 99%

Role and Therapeutic Targeting Strategies of Neutrophil Extracellular Traps in Inflammation

Li,

Xiao,

Filipczak

et al. 2023

IJN

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Neutrophil extracellular traps (NETs) are large DNA reticular structures secreted by neutrophils and decorated with histones and antimicrobial proteins. As a key mechanism for neutrophils to resist microbial invasion, NETs play an important role in the killing of microorganisms (bacteria, fungi, and viruses). Although NETs are mostly known for mediating microbial killing, increasing evidence suggests that excessive NETs induced by stimulation of physical and chemical components, microorganisms, and pathological factors can exacerbate inflammation and organ damage. This review summarizes the induction and role of NETs in inflammation and focuses on the strategies of inhibiting NETosis and the mechanisms involved in pathogen evasion of NETs. Furthermore, herbal medicine inhibitors and nanodelivery strategies improve the efficiency of inhibition of excessive levels of NETs.

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Citrullination of actin-ligand and nuclear structural proteins, cytoskeleton reorganization and protein redistribution across cellular fractions are early events in ionomycin-induced NETosis

Cited by 7 publications

References 85 publications

Targeting Myeloperoxidase Ameliorates Gouty Arthritis: A Virtual Screening Success Story

Targeting Myeloperoxidase Ameliorates Gouty Arthritis: A Virtual Screening Success Story

Nicotinamide riboside Induced Energy Stress and Metabolic Reprogramming in BEAS-2B Cells

Role and Therapeutic Targeting Strategies of Neutrophil Extracellular Traps in Inflammation

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