scholarly journals Distinct role of Sirtuin 1 (SIRT1) and Sirtuin 2 (SIRT2) in inhibiting cargo-loading and release of extracellular vesicles

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Byung Rho Lee ◽  
Bethany J. Sanstrum ◽  
Yutao Liu ◽  
Sang-Ho Kwon
Keyword(s):  
Extracellular Vesicles ◽  
Sirtuin 1 ◽  
Multivesicular Bodies ◽  
Vesicle Traffic ◽  
Cargo Protein ◽  
Extracellular Release ◽  
Golgi Network ◽  
Protein Deacetylase ◽  
Distinct Role

AbstractExosomes, vehicles for intercellular communication, are formed intracellularly within multivesicular bodies (MVBs) and are released upon fusion with the plasma membrane. For their biogenesis, proper cargo loading to exosomes and vesicle traffic for extracellular release are required. Previously we showed that the L-type lectin, LMAN2, limits trans-Golgi Network (TGN)-to-endosomes traffic of GPRC5B, an exosome cargo protein, for exosome release. Here, we identified that the protein deacetylase sirtuin 2 (SIRT2) as a novel interactor of LMAN2. Loss of SIRT2 expression resulted in exosomal release of LMAN2, a Golgi resident protein, along with increased exosomal release of GPRC5B. Furthermore, knockout of SIRT2 increased total number of extracellular vesicles (EVs), indicating increased MVB-to-EV flux. While knockout of SIRT1 increased EV release with enlarged late endolysosome, knockout of SIRT2 did not exhibit endolysosome enlargement for increased EV release. Taken together, our study suggests that SIRT2 regulates cargo loading to MVBs and MVB-to-EV flux through a mechanism distinct from that of SIRT1.

The Distinct Role of Extracellular Vesicles Derived from Normal and Cancer Stem Cells

2017 ◽  
Vol 3 (3) ◽  
pp. 218-224 ◽  
Author(s):  
Cristina Grange ◽  
Marta Tapparo ◽  
Sharad Kholia ◽  
Benedetta Bussolati ◽  
Giovanni Camussi
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Extracellular Vesicles ◽  
Distinct Role

Crossroads of the endosomal machinery: Multivesicular bodies, small extracellular vesicles and autophagy

2020 ◽  
Vol 2 (1) ◽  
pp. 48-53
Author(s):  
Julia Christina Gross ◽  
Sabnam Parbin
Keyword(s):  
Plasma Membrane ◽  
Extracellular Vesicles ◽  
Physiological Stress ◽  
Multivesicular Bodies ◽  
Endosomal Trafficking ◽  
Primary Role ◽  
Endocytic Machinery ◽  
Endosomal System ◽  
Selection Of

The primary role of endosomal system is endocytic trafficking – to sort out internalized macromolecules and proteins to their destined cellular localizations. Incorporation of sorted cargos into multivesicular bodies (MVBs) confers specificities and determines their fates. This central point of the endosomal trafficking separates MVBs in two directions. The MVB populations fuse either with lysosomes to initiate autophagy or with plasma membrane to release small extracellular vesicles. Factors contributing to the selection of cargo and direction of trafficking incorporate the cells’ metabolic status and stress level. In this review, we discuss the molecular cues responsible for differential cargo sorting into MVBs and trafficking directions of MVBs in the endosomal network. Keywords: Exosomes; degradative MVB; secretory MVB; physiological stress; endocytic machinery; lysosome

Use of riboflavinum and magnesium citrate in obstetrics and gynecology

GYNECOLOGY ◽  
2018 ◽  
Vol 20 (6) ◽  
pp. 60-66
Author(s):  
O A Gromova ◽  
I Yu Torshin ◽  
N K Tetruashvili
Keyword(s):  
Thrombus Formation ◽  
Sirtuin 1 ◽  
Obstetrics And Gynecology ◽  
Inflammatory Factor ◽  
Vitamin B2 ◽  
Magnesium Citrate ◽  
Fetal Malformations ◽  
Folate Cycle ◽  
Pro Inflammatory Cytokines

Low provision of cells with vitamin B2 and magnesium leads to a decrease in the activity of the sirtuin-1 deacetylase and an increase in the activity of the pro-inflammatory factor NF-kB, a decrease in the levels of glutathione, an increase in the levels of homocysteine, thrombus formation, the activity of mitochondria, the development of migraine, convulsions and miscarriage. The role of riboflavin in the regulation of the folate cycle in the genotype MTHFR 677TT for the prevention of folatresistant fetal malformations, the advantages of an aqueous solution of riboflavin and magnesium citrate is considered. The data on titanium dioxide, which increases the level of pro-inflammatory cytokines IL-1b, IL-4, IL-5, IL-6, G-CSF, CCL-2, CCL-3, CCL-4, are presented.

Role of Exosomes in the Exchange of Spermatozoa after Leaving the Seminiferous Tubule: A Review

2020 ◽  
Vol 21 (5) ◽  
pp. 330-338
Author(s):  
Luming Wu ◽  
Yuan Ding ◽  
Shiqiang Han ◽  
Yiqing Wang
Keyword(s):  
Drug Delivery ◽  
Plasma Membrane ◽  
Seminiferous Tubule ◽  
Metabolic Diseases ◽  
Inflammatory Diseases ◽  
Multivesicular Bodies ◽  
Extensive Search ◽  
Neurological Research ◽  
The One

Background: Exosomes are extracellular vesicles (EVs) released from cells upon fusion of an intermediate endocytic compartment with the plasma membrane. They refer to the intraluminal vesicles released from the fusion of multivesicular bodies with the plasma membrane. The contents and number of exosomes are related to diseases such as metabolic diseases, cancer and inflammatory diseases. Exosomes have been used in neurological research as a drug delivery tool and also as biomarkers for diseases. Recently, exosomes were observed in the seminal plasma of the one who is asthenozoospermia, which can affect sperm motility and capacitation. Objective: The main objective of this review is to deeply discuss the role of exosomes in spermatozoa after leaving the seminiferous tubule. Methods: We conducted an extensive search of the literature available on relationships between exosomes and exosomes in spermatozoa on the bibliographic database. Conclusion: : This review thoroughly discussed the role that exosomes play in the exchange of spermatozoa after leaving the seminiferous tubule and its potential as a drug delivery tool and biomarkers for diseases as well.

Effect of Annexins Translocated in Extracellular Vesicles on Tumorigenesis

2020 ◽  
Vol 20 ◽  
Author(s):  
Qionghui Wu ◽  
Haidong Wei ◽  
Wenbo Meng ◽  
Xiaodong Xie ◽  
Zhenchang Zhang ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Extracellular Vesicles ◽  
Immune Cell ◽  
Epithelial Mesenchymal Transition ◽  
Main Role ◽  
Tumor Cell Adhesion ◽  
Mesenchymal Transition ◽  
Calcium Dependent ◽  
Tumor Neovascularization

: Annexin, a calcium-dependent phospholipid binding protein, can affect tumor cell adhesion, proliferation, apoptosis, invasion and metastasis, as well as tumor neovascularization in different ways. Recent studies have shown that annexin exists not only as an intracellular protein in tumor cells, but also in different ways to be secret outside the cell as a “crosstalk” tool for tumor cells and tumor microenvironment, thus playing an important role in the development of tumors, such as participating in epithelial-mesenchymal transition, regulating immune cell behavior, promoting neovascularization and so on. The mechanism of annexin secretion in the form of extracellular vesicles and its specific role is still unclear. This paper summarizes the main role of annexin secreted into the extracellular space in the form of extracellular vesicles in tumorigenesis and drug resistance and analyzes its possible mechanism.

scholarly journals The role of Extracellular Vesicles during CNS development

2021 ◽  
pp. 102124
Author(s):  
Nasim Bahram Sangani ◽  
Gomes. Ana Rita ◽  
Leopold M.G. Curfs ◽  
Chris P. Reutelingsperger
Keyword(s):  
Extracellular Vesicles ◽  
Cns Development

scholarly journals The Role of Extracellular Vesicles as Shuttles of RNA and Their Clinical Significance as Biomarkers in Hepatocellular Carcinoma

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 902
Author(s):  
Eva Costanzi ◽  
Carolina Simioni ◽  
Gabriele Varano ◽  
Cinzia Brenna ◽  
Ilaria Conti ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Extracellular Vesicles ◽  
Tumor Metastasis ◽  
Biological Processes ◽  
Rna Molecules ◽  
Expression Of Genes ◽  
Non Coding Rna ◽  
Donor Cells ◽  
Relevant Role

Extracellular vesicles (EVs) have attracted interest as mediators of intercellular communication following the discovery that EVs contain RNA molecules, including non-coding RNA (ncRNA). Growing evidence for the enrichment of peculiar RNA species in specific EV subtypes has been demonstrated. ncRNAs, transferred from donor cells to recipient cells, confer to EVs the feature to regulate the expression of genes involved in differentiation, proliferation, apoptosis, and other biological processes. These multiple actions require accuracy in the isolation of RNA content from EVs and the methodologies used play a relevant role. In liver, EVs play a crucial role in regulating cell–cell communications and several pathophysiological events in the heterogeneous liver class of cells via horizontal transfer of their cargo. This review aims to discuss the rising role of EVs and their ncRNAs content in regulating specific aspects of hepatocellular carcinoma development, including tumorigenesis, angiogenesis, and tumor metastasis. We analyze the progress in EV-ncRNAs’ potential clinical applications as important diagnostic and prognostic biomarkers for liver conditions.

scholarly journals F4/80+ Kupffer Cell-Derived Oncostatin M Sustains the Progression Phase of Liver Regeneration through Inhibition of TGF-β2 Pathway

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2231
Author(s):  
Qingjun Lu ◽  
Hao Shen ◽  
Han Yu ◽  
Jing Fu ◽  
Hui Dong ◽  
...  
Keyword(s):  
Liver Regeneration ◽  
Serum Levels ◽  
Inhibitory Effect ◽  
Regenerative Process ◽  
Oncostatin M ◽  
Hepatocyte Proliferation ◽  
Initiation Phase ◽  
Distinct Role

The role of Kupffer cells (KCs) in liver regeneration is complicated and controversial. To investigate the distinct role of F4/80+ KCs at the different stages of the regeneration process, two-thirds partial hepatectomy (PHx) was performed in mice to induce physiological liver regeneration. In pre- or post-PHx, the clearance of KCs by intraperitoneal injection of the anti-F4/80 antibody (α-F4/80) was performed to study the distinct role of F4/80+ KCs during the regenerative process. In RNA sequencing of isolated F4/80+ KCs, the initiation phase was compared with the progression phase. Immunohistochemistry and immunofluorescence staining of Ki67, HNF-4α, CD-31, and F4/80 and Western blot of the TGF-β2 pathway were performed. Depletion of F4/80+ KCs in pre-PHx delayed the peak of hepatocyte proliferation from 48 h to 120 h, whereas depletion in post-PHx unexpectedly led to persistent inhibition of hepatocyte proliferation, indicating the distinct role of F4/80+ KCs in the initiation and progression phases of liver regeneration. F4/80+ KC depletion in post-PHx could significantly increase TGF-β2 serum levels, while TGF-βRI partially rescued the impaired proliferation of hepatocytes. Additionally, F4/80+ KC depletion in post-PHx significantly lowered the expression of oncostatin M (OSM), a key downstream mediator of interleukin-6, which is required for hepatocyte proliferation during liver regeneration. In vivo, recombinant OSM (r-OSM) treatment alleviated the inhibitory effect of α-F4/80 on the regenerative progression. Collectively, F4/80+ KCs release OSM to inhibit TGF-β2 activation, sustaining hepatocyte proliferation by releasing a proliferative brake.

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