Extracellular vesicles from amyloid-β exposed cell cultures induce severe dysfunction in cortical neurons
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Abstract Alzheimer’s disease (AD) is characterized by a substantial loss of neurons and synapses throughout the brain. The exact mechanism behind the neurodegeneration is still unclear, but recent data suggests that spreading of amyloid-β (Aβ) pathology via extracellular vesicles (EVs) may contribute to disease progression. We have previously shown that an incomplete degradation of Aβ 42 protofibrils by astrocytes results in the release of EVs containing neurotoxic Aβ. Here, we describe the cellular mechanisms behind EV-associated neurotoxicity in detail. EVs were isolated from untreated and Aβ 42 protofibril exposed neuroglial co-cultures, consisting mainly of astrocytes. The EVs were added to cortical neurons for 2 or 4 days and the neurodegenerative processes were followed with immunocytochemistry, time-lapse imaging and transmission electron microscopy (TEM). Addition of EVs from Aβ 42 protofibril exposed co-cultures resulted in synaptic loss, severe mitochondrial impairment and apoptosis. TEM analysis demonstrated that the EVs induced axonal swelling and vacuolization of the neuronal cell bodies. Interestingly, EV exposed neurons also displayed pathological lamellar bodies of cholesterol deposits in lysosomal compartments. Taken together, our data show that the secretion of EVs from Aβ exposed cells induces neuronal dysfunction in several ways, indicating a central role for EVs in the progression of Aβ-induced pathology.Keywords:
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Amyloid (mycology)
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Communication between cells is particularly important during tumour progression. Communication can take place through direct cell–cell interactions, but also through extracellular secretion of mediators acting at a distance. These mediators can be either soluble molecules or more complex structures called membrane vesicles, enclosing soluble factors within a lipid bilayer. A variety of extracellular membrane vesicles have been described, for instance microvesicles, ectosomes and a subtype called exosomes. The role of exosomes in tumour progression has been studied extensively in the last 10 years. In the present mini-review, we discuss our recent results, first showing the heterogeneity of the vesicles called exosomes and the probable existence of subpopulations of these exosomes, and secondly demonstrating that in vivo secretion of exosomes by some tumours can promote tumour progression, but that such a function cannot be generalized to all tumours and all exosomes.
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Extracellular vesicles (EV) are shed by tumor cells but little is known about their individual molecular phenotypes and heterogeneity. While exosomes have received considerable attention, much less is known about larger microvesicles. Here we profile single microvesicles (MV) and exosomes from glioblastoma (GB) cells and MV from the plasma of patients.
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// 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.
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Objectives: To observe the effects of Moringa Oleifera leaves extract on BPA induced changes (Diameter of hepatocytes and vacuolization) in liver of rats.
Study Design: Experimental study, conducted at Post Graduate Medical Institute.
Methodology: This study was performed on 32 adult rats for seven weeks. They were divided into 4 equal groups A, B, C and D. Group A was control received corn oil only. Group B, received BPA only 50mg/kg/bw. Group C and D received BPA 50mg/kg along with MoLE 250mg and 500mg. Liver was removed and was fixed in 10% formalin. To observe the effect of BPA and MoLE, slides were prepared for histological examination. For Hepatocytes, diameter and vacuolization was observed. The statistical analysis of results was done by using SPSS 21.
Result: In group B, vacuolization (87.5% of animals) and statistical significant increase in mean diameter (19.7±1.3) of hepatocytes was seen. Presence of vacuoles has presumably lead to an increase in diameter . However in Groups C 50% of animals showed vacuolization and mean mean hepatocyte diameter was 17.0±1.1. In Group D 25% of animals showed vacuolization and mean mean hepatocyte diameter decreased to14.6±1 after administration of MoLE.
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Previous studies have reported that striking variations in hepatocellular vacuolization occurs in rabbits and the magnitude of vacuolization correlated independently with weight and sex. The current study evaluated the effects of feed restriction and gonadectomy on this hepatocellular vacuolization. For 28 days, rabbits were fed either ad libitum (ad lib group), 100% of the National Research Council's recommended feed intake required for growth (100% group), or 50% of the NRC recommended feed intake required for growth (50% group). Feed consumption, weight gain, final body weight, absolute liver weight, and relative liver weight were not significantly different between the ad lib and 100% groups. Values for these parameters for both groups were significantly greater than for the 50% group. Rabbits in the 50% group had significantly less hepatocellular vacuolization than rabbits in the 100% group. Hepatocellular vacuolization in the 100% group did not differ from rabbits fed ad libitum. Hepatocellular vacuolization in the ad lib group was greater than in the 50% group but this difference was not significant. Ovariectomy and orchiectomy did not significantly alter hepatocellular vacuolization in either female or male rabbits, respectively, that were fed ad libitum for 28 days. However, intact females had significantly greater hepatocellular vacuolization than either intact or orchiectomized males. Conversely, hepatocellular vacuolization in ovariectomized females was not significantly different from that in intact and orchiectomized males. There were no significant differences in feed consumption, weight gain, final body weight, and absolute and relative liver weights among these intact and gonadectomized groups. Results of these studies indicate feed consumption can affect the degree of hepatocellular vacuolization in rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)
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Exosomes are nanosized lipid vesicles released from cells. They are capable of transferring proteins, mRNA, and miRNA between cells and, therefore, represent a potential means of intercellular communication. Exosomes can be proangiogenic and may have cardioprotective properties. In contrast, their larger cousins, microvesicles, seem to have generally detrimental effects that are prothrombotic and proinflammatory. Exosomes are released from multivesicular bodies via an exocytic pathway and have the potential for cell-specific targeting. This normal process is hijacked during various pathological conditions, such as cancer, viral infection, and amyloidopathies. We assess the evidence for a role of exosomes and microvesicles in normal cardiovascular physiology, as well as during cardiovascular disease. In addition to offering a potential source of cardiovascular biomarkers, exosomes may offer a nonimmunogenic means of manipulating the heart.
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The objective is to establish a simple,convenient,accurate,specific method to detect the NDV and detect the location of NDV in the COS-7 by comparing the indirect HRP-immunocytochemistry and indirect fluorescence immunocytochemistry.Both two experiment methods can detect the location of NDV and it was in the cell plasm of the COS-7.The indirect HRP-immunocytochemistry request the dilution of the first antibody is less than 1∶100,but the indirect fluorescence immunocytochemistry request the dilution of the first antibody is less than 1∶100.The indirect HRP-immunocytochemistry request the dilution of the second antibody is less than 1∶300,but the indirect fluorescence immunocytochemistry request the dilution of the second antibody is less than 1∶50.Further more,when detect the results that the indirect HRP-immunocytochemistry is more convenient than the indirect fluorescence immunocytochemistry.The indirect HRP-immunocytochemistry is simple,convenient,accurate and specific method to detect the NDV.
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This editorial article introduces the new scientific journal Exosomes and Microvesicles (EXMV), the official journal of the American Society for Exosomes and Microvesicles (ASEMV), and describes its editorial line and mission in relation to the role of the Society, the state of the art of the study of exosomes and microvesicles, and the overall approach of the publication.
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