Divalent Metal Transporter 1 Knock-Down Modulates IL-1β Mediated Pancreatic Beta-Cell Pro-Apoptotic Signaling Pathways through the Autophagic Machinery

Kang, Taewook; Huang, Honggang; Mandrup‐Poulsen, Thomas; Larsen, Martin Jakob

doi:10.3390/ijms22158013

Cited by 6 publications

(4 citation statements)

References 123 publications

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“…Interestingly, in regard to inflammation there is a report that pro-inflammatory cytokines promote cellular iron uptake by up-regulation of DMT1 expression in pancreatic β-cells inducing cell death [58], while DMT1 silencing has a protective role. The signalling pathway in this phenomenon has not been fully clarified.…”

Section: Acidosis-dependent Inflammation and Iron Homeostasismentioning

confidence: 99%

Iron Overload Accompanying Extracellular Acidosis and Neurodegeneration

Ingrassia,

Garrick

2024

Preprint

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The dynamic equilibrium of iron homeostasis has an important role in sustaining metabolic and neurological functions during human life. Iron excretion is modest and unregulated hence this overall equilibrium is tightly regulated in normal conditions by increasing deficient or limiting excessive iron assimilation. Here we focus on neural tissue overload, dyshomeostasis that is preceded by excessive assimilation, disturbances in internal homeostasis or both. Normal steps in iron homeostasis include its uptake across the apical membrane of the enterocytes in a mildly acidic duodenal milieu by the major importer of ferrous iron, Divalent Metal Transporter 1 (DMT1) (Nramp2/DCT1/SLC11A2, solute carrier family 11 member 2) [1, 2], responsible for the uptake of Non-Transferrin Bound Iron (NTBI) and divalent metals [3], passage through enterocytes bound to a chaperone and crossing the basal membrane via the only known cellular ferrous iron exporter, ferroportin [4] with the iron bound to transferrin (Tf) as it exits. Cells in peripheral tissues largely utilize circulating iron after uptake by receptor-mediated endocytosis of Tf-bound Iron [5]. Derangement of duodenal NTBI absorption of iron and heavy metals is influenced by systemic iron metabolism associated with inflammation that leads to iron accumulation into peripheral tissues and potential development of neurodegenerative diseases, involving distribution and fine regulation of DMT1 also in the central nervous system, where inflammatory-related acidosis influences DMT1 uptake, via its action as a proton cotransporter. Pharmacological strategies to inhibit NTBI transport selectively will be illustrated in relationship to protection, particularly neuroprotection, against iron overload associated with acidosis, inflammation, neuroinflammation and subsequent neurodegeneration.

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Section: Acidosis-dependent Inflammation and Iron Homeostasismentioning

confidence: 99%

Iron Overload Accompanying Extracellular Acidosis and Neurodegeneration

Ingrassia,

Garrick

2024

Preprint

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“…For example, both of TNF-α and IL-1β can inhibit insulin signaling from activation by suppressing IRS-1 phosphorylation. 137–139 Besides, they can regulate the expression and function of many metabolism-related signals such as PPAR-γ, suppressor of cytokine signaling (SOCS), and adiponectin. 140 , 141 Based on this understanding, it was assumed that the anti-IR effects from JNK1 knockdown in adipose tissues may be caused by the decreased production of inflammatory mediators like IL-6.…”

Section: Key Pathways Involved In Ra Metabolism Alterationmentioning

confidence: 99%

“…For example, both of TNF-α and IL-1β can inhibit insulin signaling from activation by suppressing IRS-1 phosphorylation. [137][138][139] Besides, they can regulate the expression and function of many metabolism-related signals such as PPAR-γ, suppressor of cytokine signaling (SOCS), and adiponectin. 140,141 https://doi.org/10.2147/JIR.S398291…”

Section: Jnkmentioning

confidence: 99%

The Involvement of Glucose and Lipid Metabolism Alteration in Rheumatoid Arthritis and Its Clinical Implication

Luo¹,

Wu²,

Yin³

et al. 2023

JIR

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Obviously, immune cells like T cells and macrophages play a major role in rheumatoid arthritis (RA). On one hand, the breakdown of immune homeostasis directly induces systemic inflammation; on the other hand, these cells initiate and perpetuate synovitis and tissue damages through the interaction with fibroblast-like synoviocytes (FLS). In recent years, the pathological link between metabolic disorders and immune imbalance has received increasing attention. High energy demand of immune cells leads to the accumulation of metabolic byproducts and inflammatory mediators. They act on various metabolism-sensitive signal pathways as well as relevant transcription factors, such as HIF-1α, and STATs. These molecular events will impact RA-related effectors like circulating immune cells and joint-resident cells in return, allowing the continuous progression of systemic inflammation, arthritic manifestations, and life-threatening complications. In other words, metabolic complications are secondary pathological factors for the progression of RA. Therefore, the status of energy metabolism may be an important indicator to evaluate RA severity, and in-depth explorations of the mechanisms underlying the mystery of how RA-related metabolic disorders develop will provide useful clues to further clarify the etiology of RA, and inspire the discovery of new anti-rheumatic targets. This article reviews the latest research progress on the interactions between immune and metabolism systems in the context of RA. Great importance is attached to the changes in certain pathways controlling both immune and metabolism functions during RA progression.

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“…This needs to be verified in pyroptosis-mediated periodontitis, which is usually a severe inflammatory condition. Besides, IL-1β is also reported to upregulate apoptotic signaling pathways ( Guadagno et al., 2015 ; Liang et al., 2018 ; Wang et al., 2019 ; Kang et al., 2021 ), autophagy ( Romagnoli et al., 2018 ), and oxidative stress and is thus involved in tissue damage through inflammatory independent pathways ( Zhu et al., 2015 ; Wang et al., 2021 ).…”

Section: Role Of Pyroptosis-regulated Cell Death Mechanisms In Period...mentioning

confidence: 99%

Pyroptosis in periodontitis: From the intricate interaction with apoptosis, NETosis, and necroptosis to the therapeutic prospects

Zhang

Xia

et al. 2022

Front. Cell. Infect. Microbiol.

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Periodontitis is highly prevalent worldwide. It is characterized by periodontal attachment and alveolar bone destruction, which not only leads to tooth loss but also results in the exacerbation of systematic diseases. As such, periodontitis has a significant negative impact on the daily lives of patients. Detailed exploration of the molecular mechanisms underlying the physiopathology of periodontitis may contribute to the development of new therapeutic strategies for periodontitis and the associated systematic diseases. Pyroptosis, as one of the inflammatory programmed cell death pathways, is implicated in the pathogenesis of periodontitis. Progress in the field of pyroptosis has greatly enhanced our understanding of its role in inflammatory diseases. This review first summarizes the mechanisms underlying the activation of pyroptosis in periodontitis and the pathological role of pyroptosis in the progression of periodontitis. Then, the crosstalk between pyroptosis with apoptosis, necroptosis, and NETosis in periodontitis is discussed. Moreover, pyroptosis, as a novel link that connects periodontitis with systemic disease, is also reviewed. Finally, the current challenges associated with pyroptosis as a potential therapeutic target for periodontitis are highlighted.

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Divalent Metal Transporter 1 Knock-Down Modulates IL-1β Mediated Pancreatic Beta-Cell Pro-Apoptotic Signaling Pathways through the Autophagic Machinery

Cited by 6 publications

References 123 publications

Iron Overload Accompanying Extracellular Acidosis and Neurodegeneration

Iron Overload Accompanying Extracellular Acidosis and Neurodegeneration

The Involvement of Glucose and Lipid Metabolism Alteration in Rheumatoid Arthritis and Its Clinical Implication

Pyroptosis in periodontitis: From the intricate interaction with apoptosis, NETosis, and necroptosis to the therapeutic prospects

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