Optical Nanoscopy of Cytokine-Induced Structural Alteration of Endoplasmic Reticulum and Golgi Apparatus in Insulin Secreting Cells

Published: Aug. 14, 2024

Pro-inflammatory cytokines play a role in the failure of β-cells type 1 and 2 diabetes. While existing data from ‘omics’ experiments allow for some understanding molecular mechanisms behind cytokine-induced dysfunction β-cells, no report thus far has provided information on direct imaging β-cell landscape with nanoscale resolution following cytokine exposure. In this study, we use Airyscan-based optical super-resolution microscopy Insulinoma 1E (INS-1E) cells to investigate structural properties two subcellular membranous compartments involved production, maturation secretion insulin-containing granules, Endoplasmic Reticulum (ER) Golgi Apparatus (GA). Our findings reveal that exposure INS-1E IL-1β IFN-γ 24 hours leads significant alterations both compartments. more detail, ER GA fragment give rise vesicle-like structures markedly reduced characteristic area perimeter increased circularity respect original structures. These complement collected these their using lay ground future optical-microscopy-based ex-vivo in-vivo investigations.

Language: Английский

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Membrane tension sensing formin-binding protein 1 is a neuronal nutrient stress-responsive Golgiphagy receptor

Metabolism, Journal Year: 2024, Volume and Issue: unknown, P. 156040 - 156040

Published: Sept. 1, 2024

Language: Английский

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FTD/ALS Type 7-Associated Thr104Asn Mutation of CHMP2B Blunts Neuronal Process Elongation, and Is Recovered by Knockdown of Arf4, the Golgi Stress Regulator

Neurology International, Journal Year: 2023, Volume and Issue: 15(3), P. 980 - 993

Published: Aug. 11, 2023

Frontotemporal dementia and/or amyotrophic lateral sclerosis type 7 (FTD/ALS7) is an autosomal dominant neurodegenerative disorder characterized by the onset of FTD ALS, mainly in adulthood. Patients with some types mutations, including Thr104Asn (T104N) mutation charged multivesicular body protein 2B (CHMP2B), have predominantly ALS phenotypes, whereas patients other mutations phenotypes. A few result having both phenotypes approximately equally; however, reason why differ depending on position unknown. CHMP2B comprises one part endosomal sorting complexes required for transport (ESCRT), specifically ESCRT-III, cytoplasm. We describe here, first time, that T104N inhibits neuronal process elongation N1E-115 cell line, a model line undergoing differentiation. This inhibitory phenotype was accompanied changes marker expression. Of note, mutation, but not wild-type form, preferentially accumulated Golgi body. four major stress signaling pathways currently known, pathway through Arf4, small GTPase, upregulated cells expressing mutation. Conversely, knockdown Arf4 cognate interfering (si)RNA recovered inhibited These results suggest morphological differentiation triggering signaling, revealing possible therapeutic molecular target recovering potential and cellular underlying FTD/ALS7.

Language: Английский

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Function and regulation of nitric oxide signaling in Drosophila

Molecules and Cells, Journal Year: 2023, Volume and Issue: 47(1), P. 100006 - 100006

Published: Dec. 20, 2023

Nitric oxide (NO) serves as an evolutionarily conserved signaling molecule that plays important role in a wide variety of cellular processes. Extensive studies Drosophila melanogaster have revealed NO is required for development, physiology, and stress responses many different types cells. In neuronal cells, multiple pathways appear to operate combinations regulate learning memory formation, synaptic transmission, selective connections, axon degeneration, regrowth. During organ elevated suppresses cell cycle progression, whereas downregulated leads increase larval body size via modulation hormone signaling. The most striking feature the synthase various stressors, such neuropeptides, aberrant proteins, hypoxia, bacterial infection, mechanical injury, can activate synthase, initially regulating physiology enable cells survive. However, under severe or pathophysiological conditions, high levels promote regulated death development neurodegenerative diseases. this review, I highlight discuss current understanding molecular mechanisms by which regulates distinct functions behaviors.

Language: Английский

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Modulating Golgi Stress Signaling Ameliorates Cell Morphological Phenotypes Induced by CHMP2B with Frontotemporal Dementia-Associated p.Asp148Tyr

Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(2), P. 1398 - 1412

Published: Feb. 5, 2024

Some charged multivesicular body protein 2B (CHMP2B) mutations are associated with autosomal-dominant neurodegenerative frontotemporal dementia and/or amyotrophic lateral sclerosis type 7 (FTDALS7). The main aim of this study is to clarify the relationship between expression mutated CHMP2B displaying FTD symptoms and defective neuronal differentiation. First, we illustrate that Asp148Tyr (D148Y) mutation, which preferentially displays phenotypes, blunts neurite process elongation in rat primary cortical neurons. Similar results were observed N1E-115 cell line, a model undergoes elongation. Second, these effects also accompanied by changes differentiation marker expression. Third, wild-type was indeed localized endosomal sorting complexes required transport (ESCRT)-like structures throughout cytoplasm. In contrast, D148Y mutation exhibited aggregation-like accumulated Golgi body. Fourth, among currently known stress regulators, levels Hsp47, has protective on body, decreased cells expressing mutation. Fifth, Arf4, another stress-signaling molecule, increased mutant-expressing cells. Finally, when transfecting Hsp47 or knocking down Arf4 small interfering (si)RNA, cellular phenotypes recovered. These suggest acting through signaling, negatively involved regulation morphological differentiation, providing evidence molecule controlling may be one potential therapeutic targets at molecular levels.

Language: Английский

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GOLPH3 knockdown alleviates the inflammation and apoptosis in lipopolysaccharide-induced acute lung injury by inhibiting Golgi stress mediated autophagy

Prostaglandins & Other Lipid Mediators, Journal Year: 2024, Volume and Issue: 174, P. 106865 - 106865

Published: June 28, 2024

Language: Английский

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Optical Nanoscopy of Cytokine-Induced Structural Alterations of the Endoplasmic Reticulum and Golgi Apparatus in Insulin-Secreting Cells

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(19), P. 10391 - 10391

Published: Sept. 27, 2024

Pro-inflammatory cytokines play a role in the failure of β cells type 1 and 2 diabetes. While existing data from ‘omics’ experiments allow for some understanding molecular mechanisms behind cytokine-induced dysfunction cells, no report thus far has provided information on direct imaging cell landscape with nanoscale resolution following cytokine exposure. In this study, we use Airyscan-based optical super-resolution microscopy Insulinoma 1E (INS-1E) to investigate structural properties two subcellular membranous compartments involved production, maturation secretion insulin-containing granules, endoplasmic reticulum (ER) Golgi apparatus (GA). Our findings reveal that exposure INS-1E IL-1β IFN-γ 24 h leads significant alterations both compartments. more detail, ER GA fragment give rise vesicle-like structures markedly reduced characteristic area perimeter increased circularity respect original structures. These complement collected these their lay groundwork future microscopy-based ex vivo investigations.

Language: Английский

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Giantin mediates Golgi localization of Gal3-O-sulfotransferases and affects salivary mucin sulfation in Sjögren’s disease patients

JCI Insight, Journal Year: 2024, Volume and Issue: 9(22)

Published: Oct. 10, 2024

Sjögren's disease is a chronic autoimmune characterized by symptoms of oral and ocular dryness extraglandular manifestations. Mouth not only due to reduced saliva volume, but also alterations in the quality salivary mucins patients with disease. Mucins play leading role mucosa hydration protection, where sulfated sialylated oligosaccharides retain water molecules at epithelial surface. The correct localization glycosyltransferases sulfotransferases within Golgi apparatus determines adequate O-glycosylation sulfation mucins, which depends on specific golgins that tether enzyme-bearing vesicles. Here, we show golgin called Giantin was mislocalized glands from formed protein complexes Gal3-O-sulfotransferases (Gal3STs), changed their Giantin-knockout -knockdown cells. Our results suggest could Gal3ST-bearing vesicles its altered affect Gal3ST activity, explaining decreased MUC5B observed

Language: Английский

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Endothelial NMMHC IIA dissociation from PAR1 activates the CREB3/ARF4 signaling in thrombin-mediated intracerebral hemorrhage

Journal of Advanced Research, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

There is an urgent need for cerebroprotective interventions to improve the suboptimal outcomes with intracerebral hemorrhage (ICH). Despite important role of nonmuscle myosin heavy chain IIA (NMMHC IIA) in blood-brain barrier (BBB), its function ICH remains unclear.

Language: Английский

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Electroacupuncture pretreatment ameliorates Golgi stress and the inflammation response against endotoxin-induced lung injury

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 146, P. 113868 - 113868

Published: Dec. 21, 2024

Language: Английский

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