Activation of human macrophage sodium channels regulates RNA processing to increase expression of the DNA repair protein PPP1R10

White, Chelsea R.; Dungan, Matthew; Carrithers, Michael D.

doi:10.1016/j.imbio.2018.10.005

Cited by 8 publications

(6 citation statements)

References 24 publications

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“…Human macrophage SCN5A was furthermore found to act as a pathogen sensor, initiating signalling and transcription of immune response genes for antiviral host defence, enhancing the anti-inflammatory profile of macrophages [159]. More recently, it was concluded that human macrophage SCN5A mediates an innate immune signalling pathway that limits DNA damage through increased expression of PPP1R10 , a regulator of phosphatase activity and DNA repair [160]. As discussed in a previous section, Nav1.5 expression has been found in late endosomes and phagolysosomes of macrophages within active MS lesions, where they likely participate in the phagocytic pathway of myelin degradation [145]; moreover, transfer of macrophages expressing Nav1.5 into mice with experimentally induced autoimmune encephalomyelitis promoted recovery [161].…”

Section: Scn5a/nav15 (Dys)function Immune Response and Inflammationmentioning

confidence: 99%

SCN5A channelopathy: arrhythmia, cardiomyopathy, epilepsy and beyond

Remme

2023

Phil. Trans. R. Soc. B

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Influx of sodium ions through voltage-gated sodium channels in cardiomyocytes is essential for proper electrical conduction within the heart. Both acquired conditions associated with sodium channel dysfunction (myocardial ischaemia, heart failure) as well as inherited disorders secondary to mutations in the gene SCN5A encoding for the cardiac sodium channel Nav1.5 are associated with life-threatening arrhythmias. Research in the last decade has uncovered the complex nature of Nav1.5 distribution, function, in particular within distinct subcellular subdomains of cardiomyocytes. Nav1.5-based channels furthermore display previously unrecognized non-electrogenic actions and may impact on cardiac structural integrity, leading to cardiomyopathy. Moreover, SCN5A and Nav1.5 are expressed in cell types other than cardiomyocytes as well as various extracardiac tissues, where their functional role in, e.g. epilepsy, gastrointestinal motility, cancer and the innate immune response is increasingly investigated and recognized. This review provides an overview of these novel insights and how they deepen our mechanistic knowledge on SCN5A channelopathies and Nav1.5 (dys)function. This article is part of the theme issue ‘The heartbeat: its molecular basis and physiological mechanisms’.

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Section: Scn5a/nav15 (Dys)function Immune Response and Inflammationmentioning

confidence: 99%

SCN5A channelopathy: arrhythmia, cardiomyopathy, epilepsy and beyond

Remme

2023

Phil. Trans. R. Soc. B

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“…To further understand the mechanism of ZJP treatment and the relationship between chemical components and metabolites, we combined network pharmacology to establish a "compounds-disease targets-metabolites" interaction network. e results showed that 124 chemical components from ZJP directly acted on 12 potential protein targets, indicating that multiple components in ZJP are involved in regulating endogenous metabolic changes and Twelve targets are closely associated with inflammation, including MAPK1, PTGS2, PTGS1, RXRA, ADRA1B, RB1, ADRB1, E2F1, SCN5A, PKIAIGF2, and GABRA1 [33][34][35][36]. erefore, in order to verify the accuracy of network pharmacology prediction and clarify the underlying mechanism of ZJP, we further tested the expression of these genes in gastric tissue.…”

Section: Discussionmentioning

confidence: 99%

Study of Zuojin Pill in Treating Chronic Atrophic Gastritis by UPLC-Q-TOF/MS Based on Serum and Urine Metabolomics Combined with Network Pharmacology

Chen

Liu

et al. 2021

International Journal of Analytical Chemistry

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Zuojin Pill (ZJP) is widely used for the treatment of gastrointestinal diseases, while its specific mechanism has not been systematically investigated. The aim of this study was to explore the therapeutic effects and potential mechanism of ZJP in chronic atrophic gastritis (CAG) through UPLC-Q-TOF/MS-based metabolomics combined with network pharmacology. ZJP and omeprazole significantly reduce contents of IL-1β, IL-6, IL-10, and iNOS and improve pathological characteristics. Metabolomic results indicated that the therapeutic effects of ZJP were mainly related to ten metabolites, namely, choline, L-threonine, hydroxypyruvic acid, creatine, taurine, succinic acid, cis-aconitic acid, citric acid, succinic acid semialdehyde, and uric acid. Pathway analysis showed that the treatment of CAG by ZJP was associated with taurine and hypotaurine metabolism; glyoxylate and dicarboxylate metabolism; glycine, serine, and threonine metabolism; glycerophospholipid metabolism; citrate cycle (TCA cycle), alanine, aspartate, and glutamate metabolism; butanoate metabolism; and purine metabolism. Validation of metabolic markers and key targets of network pharmacology through RT-PCR analysis showed that ZJP significantly downregulated a series of inflammatory markers, such as MAPK1, PKIA, RB1, SCN5A, RXRA, E2F1, PTGS1, IGF2, ADRB1, ADRA1B, PTGS2, and GABRA1. This study was the first to use a combination of metabolomics and network pharmacology to clarify the therapeutic effects of ZJP on CAG and the regulation of multiple metabolic pathways.

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“…Another antigen within the top 5 in active SJIA compared to healthy controls involved in inflammatory processes is elongation factor Tu GTP binding domain containing 2 (EFTUD2) [ 66 , 67 , 68 ]. Our study showed that the reactivity against EFTUD2 increases in active disease compared to healthy controls (a in Table 2 ).…”

Section: Discussionmentioning

confidence: 99%

Patients with Systemic Juvenile Idiopathic Arthritis (SJIA) Show Differences in Autoantibody Signatures Based on Disease Activity

Krainer,

Hendling,

Siebenhandl

et al. 2023

Biomolecules

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Systemic juvenile idiopathic arthritis (SJIA) is a severe rheumatic disease in children. It is a subgroup of juvenile idiopathic arthritis (JIA; MIM #604302), which is the most common rheumatic disease in children. The diagnosis of SJIA often comes with a significant delay, and the classification between autoinflammatory and autoimmune disease is still discussed. In this study, we analyzed the immunological responses of patients with SJIA, using human proteome arrays presenting immobilized recombinantly expressed human proteins, to analyze the involvement of autoantibodies in SJIA. Results from group comparisons show several differentially reactive antigens involved in inflammatory processes. Intriguingly, many of the identified antigens had a high reactivity against proteins involved in the NF-κB pathway, and it is also notable that many of the detected DIRAGs are described as dysregulated in rheumatoid arthritis. Our data highlight novel proteins and pathways potentially dysregulated in SJIA and offer a unique approach to unraveling the underlying disease pathogenesis in this chronic arthropathy.

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Activation of human macrophage sodium channels regulates RNA processing to increase expression of the DNA repair protein PPP1R10

Cited by 8 publications

References 24 publications

SCN5A channelopathy: arrhythmia, cardiomyopathy, epilepsy and beyond

SCN5A channelopathy: arrhythmia, cardiomyopathy, epilepsy and beyond

Study of Zuojin Pill in Treating Chronic Atrophic Gastritis by UPLC-Q-TOF/MS Based on Serum and Urine Metabolomics Combined with Network Pharmacology

Patients with Systemic Juvenile Idiopathic Arthritis (SJIA) Show Differences in Autoantibody Signatures Based on Disease Activity

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