Nucleophosmin may act as an alarmin: implications for severe sepsis

Nawa, Yuko; Kikuchi, Kôichi; Tancharoen, Salunya; Meng, Xianli; Sameshima, Hisayo; Ito, Takashi; Masuda, Yoshiki; Imaizumi, Hitoshi; Hashiguchi, Teruto; Maruyama, Ikuro

doi:10.1189/jlb.1008644

Cited by 40 publications

(51 citation statements)

References 38 publications

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“…The result showed that NPM1 alone can fully protect this miRNA from RNaseA digestion (Figure 5c). It has been suggested that NPM1 may be involved in shuttling RNAs and ribosomal proteins to the cytosol (32,33,35), and in a recent report, the NPM1 protein also been found outside the cell (36). This shuttling mechanism may be relevant to a possible role in miRNA export.…”

Section: Resultsmentioning

confidence: 99%

Export of microRNAs and microRNA-protective protein by mammalian cells

Wang¹,

Zhang²,

Weber³

et al. 2010

Nucleic Acids Research

910

770

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The discovery of microRNAs (miRNAs) as a new class of regulators of gene expression has triggered an explosion of research activities, but has left many unanswered questions about how this regulation functions and how it is integrated with other regulatory mechanisms. A number of miRNAs have been found to be present in plasma and other body fluids of humans and mice in surprisingly high concentrations. This observation was unexpected in two respects: first, the fact that these molecules are present at all outside the cell at significant concentrations and second, that these molecules appear to be stable outside of the cell. In light of this it has been suggested that the biological function of miRNAs may also extend outside of the cell and mediate cell–cell communication. We report here that after serum deprivation several human cell lines tested promptly export a substantial amount of miRNAs into the culture medium and the export process is largely energy dependent. The exported miRNAs are found both within and outside of the 16.5 and 120 K centrifugation pellets which contain most of the known cell-derived vesicles, the microvesicles and exosomes. We have identified some candidate proteins involved in this system, and one of these proteins may also play a role in protecting extracellular miRNAs from degradation. Our results point to a hitherto unrecognized and uncharacterized miRNA trafficking system in mammalian cells that is consistent with the cell–cell communication hypothesis.

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Section: Resultsmentioning

confidence: 99%

Export of microRNAs and microRNA-protective protein by mammalian cells

Wang¹,

Zhang²,

Weber³

et al. 2010

Nucleic Acids Research

910

770

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“…Immunofluorescence analyses were carried out as described previously [37]. After tissues were embedded in paraffin, 6-micron thick sections were cut, deparaffinized, and rehydrated.…”

Section: Methodsmentioning

confidence: 99%

Overexpression of Receptor for Advanced Glycation End Products and High-Mobility Group Box 1 in Human Dental Pulp Inflammation

Tancharoen

Tengrungsun

Suddhasthira

et al. 2014

Mediators of Inflammation

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High mobility group box 1 (HMGB1), a nonhistone DNA-binding protein, is released into the extracellular space and promotes inflammation. HMGB1 binds to related cell signaling transduction receptors, including receptor for advanced glycation end products (RAGE), which actively participate in vascular and inflammatory diseases. The aim of this study was to examine whether RAGE and HMGB1 are involved in the pathogenesis of pulpitis and investigate the effect of Prevotella intermedia (P. intermedia) lipopolysaccharide (LPS) on RAGE and HMGB1 expression in odontoblast-like cells (OLC-1). RAGE and HMGB1 expression levels in clinically inflamed dental pulp were higher than those in healthy dental pulp. Upregulated expression of RAGE was observed in odontoblasts, stromal pulp fibroblasts-like cells, and endothelial-like cell lining human pulpitis tissue. Strong cytoplasmic HMGB1 immunoreactivity was noted in odontoblasts, whereas nuclear HMGB1 immunoreactivity was seen in stromal pulp fibroblasts-like cells in human pulpitis tissue. LPS stimulated OLC-1 cells produced HMGB1 in a dose-dependent manner through RAGE. HMGB1 translocation towards the cytoplasm and secretion from OLC-1 in response to LPS was inhibited by TPCA-1, an inhibitor of NF-κB activation. These findings suggest that RAGE and HMGB1 play an important role in the pulpal immune response to oral bacterial infection.

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“…NPM1 was recently implicated in neural and hematopoietic stem cell fitness [190, 191], mRNA splicing and stability [192, 193], and NPM1 may even act as an alarmin in the immune system [194]. NPM1 was also found to be a nuclear PIP3 receptor, and the PIP3-NPM1 complex mediates the antiapoptotic effect of neural growth factor (NGF) through inhibition of caspase activated DNase [98].…”

Section: Other Functions Of Npm1mentioning

confidence: 99%

NPM1/B23: A Multifunctional Chaperone in Ribosome Biogenesis and Chromatin Remodeling

Lindström

2011

Biochemistry Research International

263

228

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At a first glance, ribosome biogenesis and chromatin remodeling are quite different processes, but they share a common problem involving interactions between charged nucleic acids and small basic proteins that may result in unwanted intracellular aggregations. The multifunctional nuclear acidic chaperone NPM1 (B23/nucleophosmin) is active in several stages of ribosome biogenesis, chromatin remodeling, and mitosis as well as in DNA repair, replication and transcription. In addition, NPM1 plays an important role in the Myc-ARF-p53 pathway as well as in SUMO regulation. However, the relative importance of NPM1 in these processes remains unclear. Provided herein is an update on the expanding list of the diverse activities and interacting partners of NPM1. Mechanisms of NPM1 nuclear export functions of NPM1 in the nucleolus and at the mitotic spindle are discussed in relation to tumor development. It is argued that the suggested function of NPM1 as a histone chaperone could explain several, but not all, of the effects observed in cells following changes in NPM1 expression. A future challenge is to understand how NPM1 is activated, recruited, and controlled to carry out its functions.

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Nucleophosmin may act as an alarmin: implications for severe sepsis

Cited by 40 publications

References 38 publications

Export of microRNAs and microRNA-protective protein by mammalian cells

Export of microRNAs and microRNA-protective protein by mammalian cells

Overexpression of Receptor for Advanced Glycation End Products and High-Mobility Group Box 1 in Human Dental Pulp Inflammation

NPM1/B23: A Multifunctional Chaperone in Ribosome Biogenesis and Chromatin Remodeling

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