Proplatelet formation in megakaryocytes is associated with endoplasmic reticulum stress

Morishima, Nobuhiro; Nakanishi, Kazuyoshi

doi:10.1111/gtc.12384

Cited by 15 publications

(21 citation statements)

References 44 publications

(52 reference statements)

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“…Houwerzijl et al (5) demonstrated increased vacuoles, plasma membrane thickening and chromatin condensation in the mitochondria and endoplasmic reticulum (ER) of ITP megakaryocytes. This may result in endoplasmic reticulum stress, leading to autophagy (6,7). Autophagy is a biological process, where cytoplasmic macromolecules self-degrade through the lysosomal pathway (8).…”

Section: Introductionmentioning

confidence: 99%

Immune thrombocytopenia induces autophagy and suppresses apoptosis in megakaryocytes

Liu

Mei

2018

Mol Med Report

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Immune thrombocytopenia (ITP) is the main pathogenesis of excessive platelet destruction and abnormal megakaryocyte apoptosis, however, the mechanism underlying this abnormality in megakaryocytes remains to be elucidated. Since autophagy and apoptosis are closely interrelated, it can be speculated that the abnormal apoptosis of ITP megakaryocytes is associated with autophagy. To test this hypothesis, a total of 14 patients with ITP and 23 healthy controls were recruited. MEG‑01 cell line was cultured in vitro, and morphological changes were observed by light microscopy, apoptosis was evaluated by flow cytometric analysis of Annexin V‑FITC/propidium iodide staining and western blot analysis of B‑cell lymphoma (Bcl)‑2, Bcl‑associated X protein (Bax), Beclin‑1 and cleaved caspase 3. Apoptotic abnormalities and autophagy were observed in the ITP plasma group. Furthermore, Bax expression was downregulated, while Beclin‑1 was upregulated. Chloroquine can block autophagy induced by ITP and remove the ITP plasma inhibition of apoptosis. Therefore, it may be concluded that ITP may induce autophagy, the inhibition of which may be a novel treatment for ITP.

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Section: Introductionmentioning

confidence: 99%

Immune thrombocytopenia induces autophagy and suppresses apoptosis in megakaryocytes

Liu

Mei

2018

Mol Med Report

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“…A recent report suggested that endoplasmic reticulum stress could be responsible for their activation. 66 Identification of caspase targets that are cleaved in mature MK would be a convincing evidence to support the hypothesis that caspase activation is required for platelet shedding and provide insights on how the localized activation of caspases contributes to platelet formation. One of these targets could be the antiapoptotic protein livin that belongs to the inhibitor of apoptosis proteins (IAP) family.…”

Section: Caspases In Proplatelet Formation and Platelet Releasementioning

confidence: 93%

Non-apoptotic functions of caspases in myeloid cell differentiation

et al. 2017

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Subtle caspase activation is associated with the differentiation of several myeloid lineages. A tightly orchestrated dance between caspase-3 activation and the chaperone HSP70 that migrates to the nucleus to protect the master regulator GATA-1 from cleavage transiently occurs in basophilic erythroblasts and may prepare nucleus and organelle expel that occurs at the terminal phase of erythroid differentiation. A spatially restricted activation of caspase-3 occurs in maturing megakaryocytes to promote proplatelet maturation and platelet shedding in the bloodstream. In a situation of acute platelet need, caspase-3 could be activated in response to IL-1α and promote megakaryocyte rupture. In peripheral blood monocytes, colony-stimulating factor-1 provokes the formation of a molecular platform in which caspase-8 is activated, which downregulates nuclear factor-kappa B (NF-κB) activity and activates downstream caspases whose target fragments such as those generated by nucleophosmin (NPM1) cleavage contribute to the generation of resting macrophages. Human monocytes secrete mature IL-1β in response to lipopolysaccharide through an alternative inflammasome activation that involves caspase-8, a pathway that does not lead to cell death. Finally, active caspase-3 is part of the proteases contained in secretory granules of mast cells. Many questions remain on how these proteases are activated in myeloid cell lineages, which target proteins are cleaved, whereas other are protected from proteolysis, the precise role of cleaved proteins in cell differentiation and functions, and the link between these non-apoptotic functions of caspases and the death of these diverse cell types. Better understanding of these functions may generate therapeutic strategies to control cytopenias or modulate myeloid cell functions in various pathological situations.

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“…The formation of platelets is mediated by ER stress. Using ER stressor, caspase-4 was inhibited in the megakaryocytes, which enhanced platelets production (91). However, the detailed mechanism is still not clear.…”

Section: Other Immune Cellsmentioning

confidence: 99%

The Emerging Roles of Endoplasmic Reticulum Stress in Balancing Immunity and Tolerance in Health and Diseases: Mechanisms and Opportunities

Song

Riesenberg

et al. 2020

Front. Immunol.

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The endoplasmic reticulum (ER) is an organelle equipped with mechanisms for proper protein folding, trafficking, and degradation to maintain protein homeostasis in the secretory pathway. As a defense mechanism, perturbation of ER proteostasis by ER stress agents activates a cascade of signaling pathways from the ER to the nucleus known as unfolded protein response (UPR). The primary goal of UPR is to induce transcriptional and translational programs to restore ER homeostasis for cell survival. As such, defects in UPR signaling have been implicated as a key contributor to multiple diseases including metabolic diseases, degenerative diseases, inflammatory disorders, and cancer. Growing evidence support the critical role of ER stress in regulating the fate as well as the magnitude of the immune response. Moreover, the availability of multiple UPR pharmacological inhibitors raises the hope that targeting UPR can be a new strategy for immune modulation and immunotherapy of diseases. This paper reviews the principal mechanisms by which ER stress affects immune cell biology and function, with a focus of discussion on UPR-associated immunopathology and the development of potential ER stress-targeted therapeutics.Frontiers in Immunology | www.frontiersin.org Conflict of Interest: ZL serves as member of scientific advisory board for Alphamab and Henlius Biotech and has a sponsored research agreement with Bristol-Myers Squibb.The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Proplatelet formation in megakaryocytes is associated with endoplasmic reticulum stress

Cited by 15 publications

References 44 publications

Immune thrombocytopenia induces autophagy and suppresses apoptosis in megakaryocytes

Immune thrombocytopenia induces autophagy and suppresses apoptosis in megakaryocytes

Non-apoptotic functions of caspases in myeloid cell differentiation

The Emerging Roles of Endoplasmic Reticulum Stress in Balancing Immunity and Tolerance in Health and Diseases: Mechanisms and Opportunities

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