scholarly journals Embryonic developmental arrest in the annual killifish Austrolebias charrua: A proteomic approach to diapause III

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0251820
Author(s):  
Cora Chalar ◽  
Graciela Clivio ◽  
Jimena Montagne ◽  
Alicia Costábile ◽  
Analía Lima ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Shotgun Proteomics ◽  
Cytoskeletal Proteins ◽  
Ephemeral Ponds ◽  
Annual Killifish ◽  
Developmental Arrest ◽  
Proteomic Approach ◽  
Species Survival ◽  
Dependent Change ◽  
Bottom Mud

Diapause is a reversible developmental arrest faced by many organisms in harsh environments. Annual killifish present this mechanism in three possible stages of development. Killifish are freshwater teleosts from Africa and America that live in ephemeral ponds, which dry up in the dry season. The juvenile and adult populations die, and the embryos remain buried in the bottom mud until the next rainy season. Thus, species survival is entirely embryo-dependent, and they are perhaps the most remarkable extremophile organisms among vertebrates. The aim of the present study was to gather information about embryonic diapauses with the use of a “shotgun” proteomics approach in diapause III and prehatching Austrolebias charrua embryos. Our results provide insight into the molecular mechanisms of diapause III. Data are available via ProteomeXchange with identifier PXD025196. We detected a diapause-dependent change in a large group of proteins involved in different functions, such as metabolic pathways and stress tolerance, as well as proteins related to DNA repair and epigenetic modifications. Furthermore, we observed a diapause-associated switch in cytoskeletal proteins. This first glance into global protein expression differences between prehatching and diapause III could provide clues regarding the induction/maintenance of this developmental arrest in A. charrua embryos. There appears to be no single mechanism underlying diapause and the present data expand our knowledge of the molecular basis of diapause regulation. This information will be useful for future comparative approaches among different diapauses in annual killifish and/or other organisms that experience developmental arrest.

scholarly journals Metabolomics analysis of annual killifish (Austrofundulus limnaeus) embryos during aerial dehydration stress

2020 ◽  
Vol 52 (9) ◽  
pp. 408-422
Author(s):  
Daniel E. Zajic ◽  
Jason E. Podrabsky
Keyword(s):  
Molecular Mechanisms ◽  
Dry Season ◽  
Dehydration Stress ◽  
Aerial Exposure ◽  
Ephemeral Ponds ◽  
Annual Killifish ◽  
Metabolite Profiles ◽  
Aquatic Vertebrates ◽  
Austrofundulus Limnaeus ◽  
Insight Into

The annual killifish, Austrofundulus limnaeus, survives in ephemeral ponds in the coastal deserts of Venezuela. Persistence through the dry season is dependent on drought-resistant eggs embedded in the pond sediments during the rainy season. The ability of these embryos to enter drastic metabolic dormancy (diapause) during normal development enables A. limnaeus to survive conditions lethal to most other aquatic vertebrates; critical to the survival of the species is the ability of embryos to survive months and perhaps years without access to liquid water. Little is known about the molecular mechanisms that aid in survival of the dry season. This study aims to gain insight into the mechanisms facilitating survival of dehydration stress due to aerial exposure by examining metabolite profiles of dormant and developing embryos. There is strong evidence for unique metabolic profiles based on developmental stage and length of aerial exposure. Actively developing embryos exhibit more robust changes; however, dormant embryos respond in an active manner and significantly alter their metabolic profile. A number of metabolites accumulate in aerial-exposed embryos that may play an important role in survival, including the identification of known antioxidants and neuroprotectants. In addition, a number of unique metabolites not yet discussed in the dehydration literature are identified, such as lanthionine and 2-hydroxyglutarate. Despite high oxygen availability, embryos accumulate the anaerobic end product lactate. This paper offers an overview of the metabolic changes occurring that may support embryonic survival during dehydration stress due to aerial incubation, which can be functionally tested using genetic and pharmacological approaches.

scholarly journals HGAL inhibits lymphoma dissemination by interacting with multiple Cytoskeletal proteins

2021 ◽  
Author(s):  
Xiaoyu Jiang ◽  
Xiaoqing Lu ◽  
Andrew J Gentles ◽  
Dekuang Zhao ◽  
Seth A. Wander ◽  
...  
Keyword(s):  
Cell Motility ◽  
B Cell ◽  
Germinal Center ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Adaptor Protein ◽  
Cytoskeletal Proteins ◽  
Proteomic Approach

Human Germinal Center Associated Lymphoma (HGAL) is an adaptor protein specifically expressed in germinal center lymphocytes. High expression of HGAL is a predictor of prolonged survival of Diffuse Large B-Cell (DLBCL) and classical Hodgkin lymphomas. Furthermore, HGAL expression is associated with early stage DLBCL, thus potentially limiting lymphoma dissemination. In our previous studies, we demonstrated that HGAL regulates B-cell receptor signaling and cell motility in vitro and deciphered some molecular mechanisms underlying these effects. Herein, by using novel animal models for in vivo DLBCL dispersion, we demonstrate that HGAL decreases lymphoma dissemination and prolongs survival. Further, by using an unbiased proteomic approach we demonstrate that HGAL may interact with multiple cytoskeletal proteins whereby implicating a multiplicity of effects in regulating lymphoma motility and spread. Specifically, we show that HGAL interacts with tubulin and this interaction may also contribute to HGAL effects on cell motility. These findings recapitulate previous observations in humans, establish the role of HGAL in lymphoma in vivo dissemination, and explain improved survival of patients with HGAL expressing lymphomas.

scholarly journals Bioactive Ent-Kaurane Diterpenes Oridonin and Irudonin Prevent Cancer Cells Migration by Interacting with the Actin Cytoskeleton Controller Ezrin

2020 ◽  
Vol 21 (19) ◽  
pp. 7186
Author(s):  
Valentina Pagliara ◽  
Giuliana Donadio ◽  
Nunziatina De Tommasi ◽  
Giuseppina Amodio ◽  
Paolo Remondelli ◽  
...  
Keyword(s):  
Cell Migration ◽  
Actin Cytoskeleton ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Experimental Models ◽  
Cytoskeletal Proteins ◽  
Migration And Invasion ◽  
Cell Migration And Invasion ◽  
Cytoskeleton Organization ◽  
Proteomic Approach

The ent-kaurane diterpene oridonin was reported to inhibit cell migration and invasion in several experimental models. However, the process by which this molecule exerts its anti-metastatic action has not been yet elucidated. In this article, we have investigated the anti-metastatic activity of Oridonin and of one homolog, Irudonin, with the aim to shed light on the molecular mechanisms underlying the biological activity of these ent-kaurane diterpenes. Cell-based experiments revealed that both compounds are able to affect differentiation and cytoskeleton organization in mouse differentiating myoblasts, but also to impair migration, invasion and colony formation ability of two different metastatic cell lines. Using a compound-centric proteomic approach, we identified some potential targets of the two bioactive compounds among cytoskeletal proteins. Among them, Ezrin, a protein involved in the actin cytoskeleton organization, was further investigated. Our results confirmed the pivotal role of Ezrin in regulating cell migration and invasion, and indicate this protein as a potential target for new anti-cancer therapeutic approaches. The interesting activity profile, the good selectivity towards cancer cells, and the lower toxicity with respect to Oridonin, all suggest that Irudonin is a very promising anti-metastatic agent.

Cancer Proteomics: New Horizons and Insights into Therapeutic Applications

2020 ◽  
Vol 17 ◽  
Author(s):  
Perumal Subramaniana ◽  
Jaime Jacqueline Jayapalan ◽  
Puteri Shafinaz Abdul-Rahmanb
Keyword(s):  
Molecular Mechanisms ◽  
Rapid Development ◽  
New Horizons ◽  
Cancer Management ◽  
Proteomic Approach ◽  
Cancer Proteomics ◽  
Therapeutic Outcomes ◽  
A Genome ◽  
Highly Sensitive ◽  
Dimensional Electrophoresis

A proteome is an efficient rendition of a genome, unswervingly controlling various cancer processes. Molecular mechanisms of several cancer processes have been unraveled by proteomic approach. Thus far, numerous tumors of diverse status have been investigated by two-dimensional electrophoresis. Numerous biomarkers have been recognized and precise categorization of apparent lesions has led to the timely detection of various cancers in persons at peril. Currently used pioneering approaches and technologies in proteomics have led to highly sensitive assays of cancer biomarkers and improved the early diagnosis of various cancers. The discovery of novel and definite biomarker signatures further widened our perceptive of the disease and novel potent drugs for efficient and aimed therapeutic outcomes in persistent cancers have emerged. However, a major limitation, even today, of proteomics is resolving and quantifying the proteins of low abundance. Despite the rapid development of proteomic technologies and their applications in cancer management, annulling the shortcomings of present proteomic technologies and development of better methods are still desirable. The main objectives of this review are to discuss the developing aspects, merits and demerits of pharmacoproteomics, redox proteomics, novel approaches and therapies being used for various types of cancer based on proteome studies.

scholarly journals Oxygen-Dependent Changes in the N-Glycome of Murine Pulmonary Endothelial Cells

Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1947
Author(s):  
Akos Tiboldi ◽  
Johannes Führer ◽  
Wolfgang Schaubmayr ◽  
Eva Hunyadi-Gulyas ◽  
Marie Louise Zach ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Lectin Binding ◽  
Supplemental Oxygen ◽  
Redox Status ◽  
Blood Oxygenation ◽  
Glycan Structure ◽  
Pulmonary Endothelium ◽  
Proteomic Approach ◽  
Oxygen Conditions

Supplemental oxygen is frequently used together with mechanical ventilation to achieve sufficient blood oxygenation. Despite the undoubted benefits, it is vigorously debated whether too much oxygen can also have unpredicted side-effects. Uncertainty is also due to the fact that the molecular mechanisms are still insufficiently understood. The lung endothelium is covered with an exceptionally broad glycocalyx, carrying N- and O-glycans, proteoglycans, glycolipids and glycosaminoglycans. Glycan structures are not genetically determined but depend on the metabolic state and the expression level and activity of biosynthetic and glycan remodeling enzymes, which can be influenced by oxygen and the redox status of the cell. Altered glycan structures can affect cell interactions and signaling. In this study, we investigated the effect of different oxygen conditions on aspects of the glycobiology of the pulmonary endothelium with an emphasis on N-glycans and terminal sialylation using an in vitro cell culture system. We combined a proteomic approach with N-glycan structure analysis by LC-MS, qRT-PCR, sialic acid analysis and lectin binding to show that constant and intermittent hyperoxia induced time dependent changes in global and surface glycosylation. An siRNA approach identified St6gal1 as being primarily responsible for the early transient increase of α2-6 sialylated structures in response to hyperoxia.

scholarly journals Identification of Aortic Proteins Involved in Arterial Stiffness in Spontaneously Hypertensive Rats Treated With Perindopril:A Proteomic Approach

2021 ◽  
Vol 12 ◽  
Author(s):  
Danyelle S. Miotto ◽  
Aline Dionizio ◽  
André M. Jacomini ◽  
Anderson S. Zago ◽  
Marília Afonso Rabelo Buzalaf ◽  
...  
Keyword(s):  
Arterial Stiffness ◽  
Spontaneously Hypertensive Rats ◽  
Wistar Rats ◽  
Molecular Mechanisms ◽  
Rho Kinase ◽  
Vascular Wall ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Cytoskeleton Organization ◽  
Proteomic Approach

Arterial stiffness, frequently associated with hypertension, is associated with disorganization of the vascular wall and has been recognized as an independent predictor of all-cause mortality. The identification of the molecular mechanisms involved in aortic stiffness would be an emerging target for hypertension therapeutic intervention. This study evaluated the effects of perindopril on pulse wave velocity (PWV) and on the differentially expressed proteins in aorta of spontaneously hypertensive rats (SHR), using a proteomic approach. SHR and Wistar rats were treated with perindopril (SHRP) or water (SHRc and Wistar rats) for 8 weeks. At the end, SHRC presented higher systolic blood pressure (SBP, +70%) and PWV (+31%) compared with Wistar rats. SHRP had higher values of nitrite concentration and lower PWV compared with SHRC. From 21 upregulated proteins in the aortic wall from SHRC, most of them were involved with the actin cytoskeleton organization, like Tropomyosin and Cofilin-1. After perindopril treatment, there was an upregulation of the GDP dissociation inhibitors (GDIs), which normally inhibits the RhoA/Rho-kinase/cofilin-1 pathway and may contribute to decreased arterial stiffening. In conclusion, the results of the present study revealed that treatment with perindopril reduced SBP and PWV in SHR. In addition, the proteomic analysis in aorta suggested, for the first time, that the RhoA/Rho-kinase/Cofilin-1 pathway may be inhibited by perindopril-induced upregulation of GDIs or increases in NO bioavailability in SHR. Therefore, we may propose that activation of GDIs or inhibition of RhoA/Rho-kinase pathway could be a possible strategy to treat arterial stiffness.

scholarly journals LY75 Ablation Mediates Mesenchymal-Epithelial Transition (MET) in Epithelial Ovarian Cancer (EOC) Cells Associated with DNA Methylation Alterations and Suppression of the Wnt/β-Catenin Pathway

2020 ◽  
Vol 21 (5) ◽  
pp. 1848 ◽  
Author(s):  
Sadia Mehdi ◽  
Magdalena Bachvarova ◽  
Marie-Pier Scott-Boyer ◽  
Arnaud Droit ◽  
Dimcho Bachvarov
Keyword(s):  
Ovarian Cancer ◽  
Dna Methylation ◽  
Epithelial Ovarian Cancer ◽  
Molecular Mechanisms ◽  
Specific Inhibitor ◽  
Alternative Methods ◽  
Cell Phenotype ◽  
Mesenchymal Transition ◽  
Proteomic Approach ◽  
Mesenchymal Epithelial Transition

Growing evidence demonstrates that epithelial–mesenchymal transition (EMT) plays an important role in epithelial ovarian cancer (EOC) progression and spreading; however, its molecular mechanisms remain poorly defined. We have previously shown that the antigen receptor LY75 can modulate EOC cell phenotype and metastatic potential, as LY75 depletion directed mesenchymal–epithelial transition (MET) in EOC cell lines with mesenchymal phenotype. We used the LY75-mediated modulation of EMT as a model to investigate for DNA methylation changes during EMT in EOC cells, by applying the reduced representation bisulfite sequencing (RRBS) methodology. Numerous genes have displayed EMT-related DNA methylation patterns alterations in their promoter/exon regions. Ten selected genes, whose DNA methylation alterations were further confirmed by alternative methods, were further identified, some of which could represent new EOC biomarkers/therapeutic targets. Moreover, our methylation data were strongly indicative for the predominant implication of the Wnt/β-catenin pathway in the EMT-induced DNA methylation variations in EOC cells. Consecutive experiments, including alterations in the Wnt/β-catenin pathway activity in EOC cells with a specific inhibitor and the identification of LY75-interacting partners by a proteomic approach, were strongly indicative for the direct implication of the LY75 receptor in modulating the Wnt/β-catenin signaling in EOC cells.

The high-resolution mass spectrometry study of the protein composition of amyloid-like urine aggregates associated with preeclampsia

2019 ◽  
Vol 26 (2) ◽  
pp. 158-161 ◽  
Author(s):  
Victoria A Sergeeva ◽  
Natalia V Zakharova ◽  
Anna E Bugrova ◽  
Natalia L Starodubtseva ◽  
Maria I Indeykina ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
High Resolution ◽  
Pregnant Women ◽  
Congo Red ◽  
Molecular Mechanisms ◽  
High Resolution Mass Spectrometry ◽  
Protein Composition ◽  
High Resolution Mass ◽  
Proteomic Approach ◽  
Resolution Mass

The study of protein misfolding and post-translational processing abnormalities is a promising diagnostic approach for socially significant pathologies associated with the accumulation of abnormal forms of proteins. Recently, it was shown that amyloid-like aggregates can be observed in the urine of pregnant women with preeclampsia, which is the most severe hypertensive complication that can lead to fateful outcomes. The protein composition of urine aggregates may clarify the molecular mechanisms underlying the pathology and has not yet been studied in detail. Using a proteomic approach based on high-resolution mass spectrometry, we studied the protein composition of amyloid-like structures that aggregate in the presence of Congo red azo-dye in the urine of pregnant women with preeclampsia. Fragments of β-sheets of α-1-antitrypsin, complement 3, haptoglobin, ceruloplasmin, and trypstatin were identified as most likely targets for Congo red binding.

scholarly journals Beneficial Effects of Bariatric Surgery-Induced by Weight Loss on the Proteome of Abdominal Subcutaneous Adipose Tissue

2020 ◽  
Vol 9 (1) ◽  
pp. 213
Author(s):  
Bárbara María Varela-Rodríguez ◽  
Paula Juiz-Valiña ◽  
Luis Varela ◽  
Elena Outeiriño-Blanco ◽  
Susana Belén Bravo ◽  
...  
Keyword(s):  
Bariatric Surgery ◽  
Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Positive Impact ◽  
De Novo Lipogenesis ◽  
Beneficial Effects ◽  
Proteomic Approach ◽  
Subcutaneous Adipose

Bariatric surgery (BS) is the most effective treatment for obesity and has a positive impact on cardiometabolic risk and in the remission of type 2 diabetes. Following BS, the majority of fat mass is lost from the subcutaneous adipose tissue depot (SAT). However, the changes in this depot and functions and as well as its relative contribution to the beneficial effects of this surgery are still controversial. With the aim of studying altered proteins and molecular pathways in abdominal SAT (aSAT) after body weight normalization induced by BS, we carried out a proteomic approach sequential window acquisition of all theoretical mass spectra (SWATH-MS) analysis. These results were complemented by Western blot, electron microscopy and RT-qPCR. With all of the working tools mentioned, we confirmed that after BS, up-regulated proteins were associated with metabolism, the citric acid cycle and respiratory electron transport, triglyceride catabolism and metabolism, formation of ATP, pyruvate metabolism, glycolysis/gluconeogenesis and thermogenesis among others. In contrast, proteins with decreased values are part of the biological pathways related to the immune system. We also confirmed that obesity caused a significant decrease in mitochondrial density and coverage, which was corrected by BS. Together, these findings reveal specific molecular mechanisms, genes and proteins that improve adipose tissue function after BS characterized by lower inflammation, increased glucose uptake, higher insulin sensitivity, higher de novo lipogenesis, increased mitochondrial function and decreased adipocyte size.

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