Topic
Vacuolization
About: Vacuolization is a research topic. Over the lifetime, 1130 publications have been published within this topic receiving 27303 citations. The topic is also known as: Vacuolation.
Papers published on a yearly basis
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Papers
TL;DR: It is concluded that freshly dissolved h-IAPP is cytotoxic and that this cytotoxicity is mediated through an interaction of ISTAPs with cellular membranes, which may have implications for the mechanism of cell death in other diseases characterized by local amyloid formation.
Abstract: NIDDM is characterized by islet amyloid deposits and decreased beta-cell mass. Islet amyloid is derived from the locally expressed protein islet amyloid polypeptide (IAPP). While it is now widely accepted that abnormal aggregation of IAPP has a role in beta-cell death in NIDDM, the mechanism remains unknown. We hypothesized that small IAPP aggregates, rather than mature large amyloid deposits, are cytotoxic. Consistent with this hypothesis, freshly dissolved human (h)-IAPP was cytotoxic when added to dispersed mouse and human islet cells, provoking the formation of abnormal vesicle-like membrane structures in association with vacuolization and cell death. Human islet cell death occurred by both apoptosis and necrosis, predominantly between 24 and 48 h after exposure to h-IAPP. In contrast, the addition to dispersed islet cells of matured h-IAPP containing large amyloid deposits of organized fibrils was seldom associated with vesicle-like structures or features of cell death, even though the cells were often encased in the larger amyloid deposits. Based on these observations, we hypothesized that h-IAPP cytotoxicity is mediated by membrane damage induced by early h-IAPP aggregates. Consistent with this hypothesis, application of freshly dissolved h-IAPP to voltage-clamped planar bilayer membranes (a cell-free in vitro system) also caused membrane instability manifested as a marked increase in conductance, increased membrane electrical noise, and accelerated membrane breakage, effects that were absent using matured h-IAPP or rat IAPP solutions. Light-scattering techniques showed that membrane toxicity corresponded to h-IAPP aggregates containing approximately 25-6,000 IAPP molecules, an intermediate-sized amyloid particle that we term intermediate-sized toxic amyloid particles (ISTAPs). We conclude that freshly dissolved h-IAPP is cytotoxic and that this cytotoxicity is mediated through an interaction of ISTAPs with cellular membranes. Once ISTAPs mature into amyloid deposits comprising >10(6) molecules, the capacity of h-IAPP to cause membrane instability and islet cell death is significantly reduced or abolished. These data may have implications for the mechanism of cell death in other diseases characterized by local amyloid formation (such as Alzheimer's disease).
639 citations
TL;DR: This new syndrome, with associated bone marrow and exocrine pancreatic dysfunctions, differs in several respects from the syndrome of pancreatic liposis and neutropenia described by Shwachman et all and Bodian et al, and from other conditions with vacuolization of the marrow or sideroblastosis.
421 citations
TL;DR: In vivo expression of high levels of wild-type hSOD1 is not only harmful to neurons in itself, but also increases or facilitates the deleterious action of a fALS-mutant SOD1.
394 citations
TL;DR: The presence of viral particles in the renal tubular epithelium that were morphologically identical to Sars-CoV-2, and with viral arrays and other features of virus assembly, provide evidence of a productive direct infection of the kidney by SARS-Co V-2.
Abstract: Background A significant fraction of patients with coronavirus disease 2019 (COVID-19) display abnormalities in renal function. Retrospective studies of patients hospitalized with COVID-19 in Wuhan, China, report an incidence of 3%-7% progressing to ARF, a marker of poor prognosis. The cause of the renal failure in COVID-19 is unknown, but one hypothesized mechanism is direct renal infection by the causative virus, SARS-CoV-2. Methods We performed an autopsy on a single patient who died of COVID-19 after open repair of an aortic dissection, complicated by hypoxic respiratory failure and oliguric renal failure. We used light and electron microscopy to examine renal tissue for evidence of SARS-CoV-2 within renal cells. Results Light microscopy of proximal tubules showed geographic isometric vacuolization, corresponding to a focus of tubules with abundant intracellular viral arrays. Individual viruses averaged 76 µm in diameter and had an envelope studded with crown-like, electron-dense spikes. Vacuoles contained double-membrane vesicles suggestive of partially assembled virus. Conclusions The presence of viral particles in the renal tubular epithelium that were morphologically identical to SARS-CoV-2, and with viral arrays and other features of virus assembly, provide evidence of a productive direct infection of the kidney by SARS-CoV-2. This finding offers confirmatory evidence that direct renal infection occurs in the setting of AKI in COVID-19. However, the frequency and clinical significance of direct infection in COVID-19 is unclear. Tubular isometric vacuolization observed with light microscopy, which correlates with double-membrane vesicles containing vacuoles observed with electronic microscopy, may be a useful histologic marker for active SARS-CoV-2 infection in kidney biopsy or autopsy specimens.
360 citations
TL;DR: New data on the molecular mechanisms of the vacuole formation and structure are reviewed to make a deeper insight into the role of cytoplasmic vacuolization in cell death and survival.
Abstract: // Andrey V. Shubin 1,2,3,* , Ilya V. Demidyuk 1,* , Alexey A. Komissarov 1 , Lola M. Rafieva 1 and Sergey V. Kostrov 1 1 Laboratory of Protein Engineering, Institute of Molecular Genetics, Moscow, Russia 2 Laboratory of Chemical Carcinogenesis, N.N. Blokhin Russian Cancer Research Center, Moscow, Russia 3 Laboratory of Biologically Active Nanostructures, N.F. Gamaleya Institute of Epidemiology and Microbiology, Moscow, Russia * These authors contributed equally to this work Correspondence to: Andrey V. Shubin, email: // Keywords : regulated cell death, vacuolization, microbial toxins, viruses Received : February 27, 2016 Accepted : June 06, 2016 Published : June 17, 2016 Abstract Cytoplasmic vacuolization (also called cytoplasmic vacuolation) is a well-known morphological phenomenon observed in mammalian cells after exposure to bacterial or viral pathogens as well as to various natural and artificial low-molecular-weight compounds. Vacuolization often accompanies cell death; however, its role in cell death processes remains unclear. This can be attributed to studying vacuolization at the level of morphology for many years. At the same time, new data on the molecular mechanisms of the vacuole formation and structure have become available. In addition, numerous examples of the association between vacuolization and previously unknown cell death types have been reported. Here, we review these data to make a deeper insight into the role of cytoplasmic vacuolization in cell death and survival.
323 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2025 | 12 |
| 2024 | 36 |
| 2023 | 52 |
| 2022 | 96 |
| 2021 | 30 |
| 2020 | 33 |