scholarly journals Extracellular Vesicle Proteomes Shed Light on the Evolutionary, Interactive, and Functional Divergence of Their Biogenesis Mechanisms

2021 ◽  
Vol 9 ◽  
Author(s):  
Hyobin Julianne Lim ◽  
Haejin Yoon ◽  
Hyeyeon Kim ◽  
Yun-Won Kang ◽  
Ji-Eun Kim ◽  
...  
Keyword(s):  
Functional Divergence ◽  
Multivesicular Body ◽  
Extracellular Vesicle ◽  
Specific Protein ◽  
Bioactive Molecules ◽  
Cellular Respiration ◽  
Protein Markers ◽  
Evolutionary Trajectory ◽  
Systematic Analysis ◽  
General Validity

Extracellular vesicles (EVs) are membranous structures containing bioactive molecules, secreted by most cells into the extracellular environment. EVs are classified by their biogenesis mechanisms into two major subtypes: ectosomes (enriched in large EVs; lEVs), budding directly from the plasma membrane, which is common in both prokaryotes and eukaryotes, and exosomes (enriched in small EVs; sEVs) generated through the multivesicular bodies via the endomembrane system, which is unique to eukaryotes. Even though recent proteomic analyses have identified key proteins associated with EV subtypes, there has been no systematic analysis, thus far, to support the general validity and utility of current EV subtype separation methods, still largely dependent on physical properties, such as vesicular size and sedimentation. Here, we classified human EV proteomic datasets into two main categories based on distinct centrifugation protocols commonly used for isolating sEV or lEV fractions. We found characteristic, evolutionarily conserved profiles of sEV and lEV proteins linked to their respective biogenetic origins. This may suggest that the evolutionary trajectory of vesicular proteins may result in a membership bias toward specific EV subtypes. Protein–protein interaction (PPI) network analysis showed that vesicular proteins formed distinct clusters with proteins in the same EV fraction, providing evidence for the existence of EV subtype-specific protein recruiters. Moreover, we identified functional modules enriched in each fraction, including multivesicular body sorting for sEV, and mitochondria cellular respiration for lEV proteins. Our analysis successfully captured novel features of EVs embedded in heterogeneous proteomics studies and suggests specific protein markers and signatures to be used as quality controllers in the isolation procedure for subtype-enriched EV fractions.

scholarly journals Sex-Specific Differences in Extracellular Vesicle Protein Cargo in Synovial Fluid of Patients with Osteoarthritis

Life ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 337
Author(s):  
Ravindra Kolhe ◽  
Virgenal Owens ◽  
Ashok Sharma ◽  
Tae Jin Lee ◽  
Wenbo Zhi ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Protein Content ◽  
Extracellular Vesicle ◽  
Specific Protein ◽  
Paracrine Signaling ◽  
Age Related ◽  
Specific Manner ◽  
Inflammatory Processes ◽  
Novel Biomarkers ◽  
Cellular Pathways

Women are at a significantly higher risk of developing osteoarthritis (OA) compared to males. The pathogenesis of osteoarthritis (OA) in women is poorly understood. Extracellular vesicles (EVs) have been shown to play an essential role in numerous signaling processes during the pathogenesis of age-related diseases via paracrine signaling. Molecular profiling of the synovial fluid-derived EVs cargo in women may help in the discovery of novel biomarkers and therapeutics for the treatment of OA in women. Previously, we reported that synovial fluid-derived EV miRNA cargo differs in a sex-specific manner. This study aims to characterize synovial fluid-derived EV protein cargo in OA patients. Our data showed sex-specific EVs protein content in OA. We found haptoglobin, orosomucoid, and ceruloplasmin significantly up-regulated, whereas apolipoprotein down-regulated in female OA EVs. In males, we discovered β-2-glycoprotein, and complement component 5 proteins significantly up-regulated and Spt-Ada-Gcn5 acetyltransferase (SAGA)-associated factor 29 down-regulated in male OA EVs. Database for Annotation, Visualization, and Integrated Discovery (DAVID) and QuickGO analysis revealed OA-specific protein involvement in several biological, molecular, and cellular pathways, specifically in inflammatory processes. In conclusion, synovial fluid EV protein content is altered in a sex-specific manner with OA, explaining the increased prevalence and severity of OA in women.

scholarly journals Importance of between and within Subject Variability in Extracellular Vesicle Abundance and Cargo when Performing Biomarker Analyses

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 485
Author(s):  
Lauren A. Newman ◽  
Alia Fahmy ◽  
Michael J. Sorich ◽  
Oliver G. Best ◽  
Andrew Rowland ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Drug Exposure ◽  
Extracellular Vesicle ◽  
The Novel ◽  
Protein Markers ◽  
Diurnal Variability ◽  
Normal Ranges ◽  
Sampling Protocols ◽  
Subject Variability ◽  
Within Subject Variability

Small extracellular vesicles (sEV) have emerged as a potential rich source of biomarkers in human blood and present the intriguing potential for a ‘liquid biopsy’ to track disease and the effectiveness of interventions. Recently, we have further demonstrated the potential for EV derived biomarkers to account for variability in drug exposure. This study sought to evaluate the variability in abundance and cargo of global and liver-specific circulating sEV, within (diurnal) and between individuals in a cohort of healthy subjects (n = 10). We present normal ranges for EV concentration and size and expression of generic EV protein markers and the liver-specific asialoglycoprotein receptor 1 (ASGR1) in samples collected in the morning and afternoon. EV abundance and cargo was generally not affected by fasting, except CD9 which exhibited a statistically significant increase (p = 0.018). Diurnal variability was observed in the expression of CD81 and ASGR1, which significantly decreased (p = 0.011) and increased (p = 0.009), respectively. These results have potential implications for study sampling protocols and normalisation of biomarker data when considering the expression of sEV derived cargo as a biomarker strategy. Specifically, the novel finding that liver-specific EVs exhibit diurnal variability in healthy subjects should have broad implications in the study of drug metabolism and development of minimally invasive biomarkers for liver disease.

Protein biomarkers in breast cancer-derived extracellular vesicles for use in liquid biopsies

2021 ◽  
Author(s):  
Dan Li ◽  
Wenjia Lai ◽  
Di Fan ◽  
Qiaojun Fang
Keyword(s):  
Breast Cancer ◽  
Early Diagnosis ◽  
Extracellular Vesicles ◽  
Liquid Biopsy ◽  
Breast Cancer Diagnosis ◽  
Extracellular Vesicle ◽  
Detection Methods ◽  
Protein Markers ◽  
Liquid Biopsies ◽  
Diagnosis And Prognosis

Breast cancer is the most common malignant disease in women worldwide. Early diagnosis and treatment can greatly improve the management of breast cancer. Liquid biopsies are becoming convenient detection methods for diagnosing and monitoring breast cancer due to their non-invasiveness and ability to provide real-time feedback. A range of liquid biopsy markers, including circulating tumor proteins, circulating tumor cells, and circulating tumor nucleic acids, have been implemented for breast cancer diagnosis and prognosis, with each having its own advantages and limitations. Circulating extracellular vesicles are messengers of intercellular communication that are packed with information from mother cells and are found in a wide variety of bodily fluids; thus, they are emerging as ideal candidates for liquid biopsy biomarkers. In this review, we summarize extracellular vesicle protein markers that can be potentially used for the early diagnosis and prognosis of breast cancer or determining its specific subtypes.

scholarly journals Anti-Stress, Glial- and Neuro-Differentiation Potential of Resveratrol: Characterization by Cellular, Biochemical and Imaging Assays

Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 671
Author(s):  
Sajal Afzal ◽  
Sukant Garg ◽  
Divya Adiga ◽  
Yoshiyuki Ishida ◽  
Keiji Terao ◽  
...  
Keyword(s):  
Oxidative Dna Damage ◽  
Specific Protein ◽  
New Drugs ◽  
Protein Markers ◽  
Human Neuroblastoma ◽  
Differentiation Potential ◽  
Daily Lives ◽  
Rat Glioma ◽  
Age Related

Environmental stress, exhaustive industrialization and the use of chemicals in our daily lives contribute to increasing incidence of cancer and other pathologies. Although the cancer treatment has revolutionized in last 2–3 decades, shortcomings such as (i) extremely high cost of treatment, (ii) poor availability of drugs, (iii) severe side effects and (iv) emergence of drug resistance have prioritized the need of developing alternate natural, economic and welfare (NEW) therapeutics reagents. Identification and characterization of such anti-stress NEW drugs that not only limit the growth of cancer cells but also reprogram them to perform their specific functions are highly desired. We recruited rat glioma- and human neuroblastoma-based assays to explore such activities of resveratrol, a naturally occurring stilbenoid. We demonstrate that nontoxic doses of resveratrol protect cells against a variety of stresses that are largely involved in age-related brain pathologies. These included oxidative, DNA damage, metal toxicity, heat, hypoxia, and protein aggregation stresses. Furthermore, it caused differentiation of cells to functional astrocytes and neurons as characterized by the upregulation of their specific protein markers. These findings endorse multiple bioactivities of resveratrol and encourage them to be tested for their benefits in animal models and humans.

scholarly journals PTSD Susceptibility and Challenges: Pathophysiological Consequences of Behavioral Symptoms

2020 ◽  
Vol 185 (Supplement_1) ◽  
pp. 279-285
Author(s):  
Mulugu V Brahmajothi ◽  
Mohamed B Abou-Donia
Keyword(s):  
Calcium Binding ◽  
Military Service ◽  
The United States ◽  
Specific Protein ◽  
Brain Parenchyma ◽  
Enzyme Linked Immunosorbent Assay ◽  
Protein Markers ◽  
Necrosis Factor Alpha ◽  
Magnetic Resonance Imaging Mri ◽  
Subclinical Symptoms

Abstract Introduction Posttraumatic stress disorder (PTSD) can develop during the aftermath of traumatic events. Although many are impacted by several stressors, nearly 3.6% suffer from PTSD in the United States with higher incidence reported in military service personnel. Any injury to the blood-brain barrier can ignite an array of biological signaling molecules in the immune-privileged brain parenchyma, which can disrupt the synaptic neural network, resulting in altered behavior. Materials and Methods In this preliminary study, we compared 20 PTSD veterans with age-matched healthy veterans to identify plasma levels of brain-specific protein markers using enzyme-linked immunosorbent assay/immunofluorometric sandwich assay for neurotrophic factors and neuropoietic cytokines, and catalytic activity of matrix metalloproteinase (MMP) by zymography. Results We observed an increased level of glial fibrillary acidic protein, tumor necrosis factor-alpha, interleukin 6, and MMP2 and MMP9 but decreased level of brain-derived neurotrophic factor, nerve growth factor-beta, and negligible difference in astroglial marker S100 calcium-binding protein B compared to controls. Conclusion Identification of neural biomarkers is essential to understand the subclinical symptoms for the diagnosis PTSD, which may not be visible by magnetic resonance imaging (MRI/fMRI) and may take years to clinically manifest.

scholarly journals Abnormal Lysosomal Positioning and Small Extracellular Vesicle Secretion in Arterial Stiffening and Calcification of Mice Lacking Mucolipin 1 Gene

2020 ◽  
Vol 21 (5) ◽  
pp. 1713 ◽  
Author(s):  
Owais M. Bhat ◽  
Xinxu Yuan ◽  
Sarah Camus ◽  
Fadi N. Salloum ◽  
Pin-Lan Li
Keyword(s):  
Multivesicular Body ◽  
Extracellular Vesicle ◽  
Annexin Ii ◽  
High Dose ◽  
Wild Type ◽  
Phenotypic Switch ◽  
Arterial Stiffening ◽  
Vesicle Secretion ◽  
Arterial Medial Calcification ◽  
Medial Calcification

Recent studies have shown that arterial medial calcification is mediated by abnormal release of exosomes/small extracellular vesicles from vascular smooth muscle cells (VSMCs) and that small extracellular vesicle (sEV) secretion from cells is associated with lysosome activity. The present study was designed to investigate whether lysosomal expression of mucolipin-1, a product of the mouse Mcoln1 gene, contributes to lysosomal positioning and sEV secretion, thereby leading to arterial medial calcification (AMC) and stiffening. In Mcoln1−/− mice, we found that a high dose of vitamin D (Vit D; 500,000 IU/kg/day) resulted in increased AMC compared to their wild-type littermates, which was accompanied by significant downregulation of SM22-α and upregulation of RUNX2 and osteopontin in the arterial media, indicating a phenotypic switch to osteogenic. It was also shown that significantly decreased co-localization of lysosome marker (Lamp-1) with lysosome coupling marker (Rab 7 and ALG-2) in the aortic wall of Mcoln1−/− mice as compared to their wild-type littermates. Besides, Mcoln1−/− mice showed significant increase in the expression of exosome/ sEV markers, CD63, and annexin-II (AnX2) in the arterial medial wall, accompanied by significantly reduced co-localization of lysosome marker (Lamp-1) with multivesicular body (MVB) marker (VPS16), suggesting a reduction of the lysosome-MVB interactions. In the plasma of Mcoln1−/− mice, the number of sEVs significantly increased as compared to the wild-type littermates. Functionally, pulse wave velocity (PWV), an arterial stiffening indicator, was found significantly increased in Mcoln1−/− mice, and Vit D treatment further enhanced such stiffening. All these data indicate that the Mcoln1 gene deletion in mice leads to abnormal lysosome positioning and increased sEV secretion, which may contribute to the arterial stiffness during the development of AMC.

scholarly journals Differential tissue-specific protein markers of vaginal carcinoma

2009 ◽  
Vol 100 (8) ◽  
pp. 1303-1314 ◽  
Author(s):  
K Hellman ◽  
A A Alaiya ◽  
S Becker ◽  
M Lomnytska ◽  
K Schedvins ◽  
...  
Keyword(s):  
Specific Protein ◽  
Protein Markers ◽  
Tissue Specific ◽  
Vaginal Carcinoma ◽  
Differential Tissue

scholarly journals Proteomic similarity of the Littorinid snails in the evolutionary context

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8546 ◽  
Author(s):  
Arina L. Maltseva ◽  
Marina A. Varfolomeeva ◽  
Arseniy A. Lobov ◽  
Polina Tikanova ◽  
Marina Panova ◽  
...  
Keyword(s):  
Phylogenetic Tree ◽  
Evolutionary History ◽  
Geographic Location ◽  
Body Part ◽  
Specific Protein ◽  
Protein Markers ◽  
Cophenetic Correlation ◽  
Additional Information ◽  
History Of ◽  
Using Data

Background The introduction of DNA-based molecular markers made a revolution in biological systematics. However, in cases of very recent divergence events, the neutral divergence may be too slow, and the analysis of adaptive part of the genome is more informative to reconstruct the recent evolutionary history of young species. The advantage of proteomics is its ability to reflect the biochemical machinery of life. It may help both to identify rapidly evolving genes and to interpret their functions. Methods Here we applied a comparative gel-based proteomic analysis to several species from the gastropod family Littorinidae. Proteomes were clustered to assess differences related to species, geographic location, sex and body part, using data on presence/absence of proteins in samples and data on protein occurrence frequency in samples of different species. Cluster support was assessed using multiscale bootstrap resampling and the stability of clustering—using cluster-wise index of cluster stability. Taxon-specific protein markers were derived using IndVal method. Proteomic trees were compared to consensus phylogenetic tree (based on neutral genetic markers) using estimates of the Robinson–Foulds distance, the Fowlkes–Mallows index and cophenetic correlation. Results Overall, the DNA-based phylogenetic tree and the proteomic similarity tree had consistent topologies. Further, we observed some interesting deviations of the proteomic littorinid tree from the neutral expectations. (1) There were signs of molecular parallelism in two Littoraria species that phylogenetically are quite distant, but live in similar habitats. (2) Proteome divergence was unexpectedly high between very closely related Littorina fabalis and L. obtusata, possibly reflecting their ecology-driven divergence. (3) Conservative house-keeping proteins were usually identified as markers for cryptic species groups (“saxatilis” and “obtusata” groups in the Littorina genus) and for genera (Littoraria and Echinolittorina species pairs), while metabolic enzymes and stress-related proteins (both potentially adaptively important) were often identified as markers supporting species branches. (4) In all five Littorina species British populations were separated from the European mainland populations, possibly reflecting their recent phylogeographic history. Altogether our study shows that proteomic data, when interpreted in the context of DNA-based phylogeny, can bring additional information on the evolutionary history of species.

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