MOLECULAR MECHANISMS AFFECTED IN PERCA FLUVIATILIS OOCYTES IN RELATION TO THEIR REPRODUCTIVE PERFORMANCES REVEALED BY A PROTEOMIC APPROACH

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.

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

Antioxidants ◽

10.3390/antiox10121947 ◽

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.

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

Frontiers in Physiology ◽

10.3389/fphys.2021.624515 ◽

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.

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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

International Journal of Molecular Sciences ◽

10.3390/ijms21051848 ◽

2020 ◽

Vol 21 (5) ◽

pp. 1848 ◽

Cited By ~ 1

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.

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

European Journal of Mass Spectrometry ◽

10.1177/1469066719860076 ◽

2019 ◽

Vol 26 (2) ◽

pp. 158-161 ◽

Cited By ~ 2

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.

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Comparative Analysis of Skeletal Muscle Metabolites of Fish with Various Rates of Aging

Fishes ◽

10.3390/fishes4020025 ◽

2019 ◽

Vol 4 (2) ◽

pp. 25 ◽

Cited By ~ 2

Author(s):

Dmitry Maslov ◽

Oxana Trifonova ◽

Anton Mikhailov ◽

Konstantin Zolotarev ◽

Kirill Nakhod ◽

...

Keyword(s):

Skeletal Muscle ◽

Fish Species ◽

Molecular Mechanisms ◽

Direct Injection ◽

Mammalian Species ◽

Pink Salmon ◽

Perca Fluviatilis ◽

Oncorhynchus Gorbuscha ◽

Oncorhynchus Keta ◽

Group Species

Fish species exhibit great diversity rating of aging (from negligible to rapid), which gives a unique possibility for the discovery of the molecular mechanisms that determine the differences in the rate of aging. A mass spectrometric metabolic profiling of skeletal muscle of fish with various aging rates was carried out by direct injection to a quadrupole time-of-flight mass spectrometer. The first group includes long-lived fish species (pike (Esox Lucius) and sterlet (Acipenser ruthenus); the second group—species with gradual senescence such as that observed in many mammalian species of similar size (zander (Sandra lucioperca) and perch (Perca fluviatilis)) and the third group—species with very short life cycle (chum salmon (Oncorhynchus keta) and pink salmon (Oncorhynchus gorbuscha)). Multivariate analysis of metabolic profiles allowed the detecting of about 80 group-specific features associated with amino acids, lipids, biogenic amines, intermediates of glycolysis, glycogenolysis, and citric acid cycle. Possible roles in the aging process are hypothesized for the biochemical pathways of the metabolites that were altered in the different groups.

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

Journal of Clinical Medicine ◽

10.3390/jcm9010213 ◽

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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Proteomics analysis reveals diabetic kidney as a ketogenic organ in type 2 diabetes

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00308.2010 ◽

2011 ◽

Vol 300 (2) ◽

pp. E287-E295 ◽

Cited By ~ 36

Author(s):

Dongjuan Zhang ◽

Hang Yang ◽

Xiaomu Kong ◽

Kang Wang ◽

Xuan Mao ◽

...

Keyword(s):

Ketone Body ◽

Molecular Mechanisms ◽

Transforming Growth Factor ◽

Ketone Bodies ◽

Proximal Tubule Cell ◽

Diabetic Kidney ◽

Mesenchymal Transition ◽

Proteomic Approach ◽

Body Production

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. To date, the molecular mechanisms of DN remain largely unclear. The present study aimed to identify and characterize novel proteins involved in the development of DN by a proteomic approach. Proteomic analysis revealed that 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase 2 (HMGCS2), the key enzyme in ketogenesis, was increased fourfold in the kidneys of type 2 diabetic db/db mice. Consistently, the activity of HMGCS2 in kidneys and 24-h urinary excretion of the ketone body β-hydroxybutyrate (β-HB) were significantly increased in db/db mice. Immunohistochemistry, immunofluorescence, and real-time PCR studies further demonstrated that HMGCS2 was highly expressed in renal glomeruli of db/db mice, with weak expression in the kidneys of control mice. Because filtered ketone bodies are mainly reabsorbed in the proximal tubules, we used RPTC cells, a rat proximal tubule cell line, to examine the effect of the increased level of ketone bodies. Treating cultured RPTC cells with 1 mM β-HB significantly induced transforming growth factor-β1 expression, with a marked increase in collagen I expression. β-HB treatment also resulted in a marked increase in vimentin protein expression and a significant reduction in E-cadherin protein levels, suggesting an enhanced epithelial-to-mesenchymal transition in RPTCs. Collectively, these findings demonstrate that diabetic kidneys exhibit excess ketogenic activity resulting from increased HMGCS2 expression. Enhanced ketone body production in the diabetic kidney may represent a novel mechanism involved in the pathogenesis of DN.

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iTRAQ Quantitative Analysis of Multidrug Resistance Mechanisms in Human Gastric Cancer Cells

Journal of Biomedicine and Biotechnology ◽

10.1155/2010/571343 ◽

2010 ◽

Vol 2010 ◽

pp. 1-11 ◽

Cited By ~ 12

Author(s):

Huai-Dong Hu ◽

Feng Ye ◽

Da-Zhi Zhang ◽

Peng Hu ◽

Hong Ren ◽

...

Keyword(s):

Gastric Cancer ◽

Multidrug Resistance ◽

Cell Line ◽

Molecular Mechanisms ◽

Absolute Quantification ◽

Differentially Expressed ◽

Human Gastric Cancer ◽

Differentially Expressed Proteins ◽

Gastric Cancer Cells ◽

Proteomic Approach

Multidrug resistance (MDR) is a major obstacle towards a successful treatment of gastric cancer. However, the mechanisms of MDR are intricate and have not been fully understood. To elucidate the molecular mechanisms of MDR in gastric cancer, we employed the proteomic approach of isobaric tags for relative and absolute quantification (iTRAQ), followed by LC-MS/MS, using the vincristine-resistant SGC7901/VCR cell line and its parental SGC7901 cell line as a model. In total, 820 unique proteins were identified and 91 proteins showed to be differentially expressed in SGC7901/VCR compared with SGC7901. Several differentially expressed proteins were further validated by western blot analysis. Furthermore, the association of MVP, one of the highly expressed proteins in SGC7901/VCR, with MDR was verified. Our study is the first application of iTRAQ technology for MDR mechanisms analysis in gastric cancer, and many of the differentially expressed proteins identified have not been linked to MDR in gastric cancer before, which showed the value of this technology in identifying differentially expressed proteins in cancer.

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Protein Expression Profiles in an Endosymbiotic Cyanobacterium Revealed by a Proteomic Approach

Molecular Plant-Microbe Interactions ◽

10.1094/mpmi-19-1251 ◽

2006 ◽

Vol 19 (11) ◽

pp. 1251-1261 ◽

Cited By ~ 18

Author(s):

Martin Ekman ◽

Petter Tollbäck ◽

Johan Klint ◽

Birgitta Bergman

Keyword(s):

Mass Spectrometry ◽

Protein Expression ◽

Molecular Mechanisms ◽

Expression Profiles ◽

Calvin Cycle ◽

Pentose Phosphate ◽

Free Living ◽

Two Dimensional Gel Electrophoresis ◽

Proteomic Approach ◽

Nostoc Strain

Molecular mechanisms behind adaptations in the cyano-bacterium (Nostoc sp.) to a life in endosymbiosis with plants are still not clarified, nor are the interactions between the partners. To get further insights, the proteome of a Nostoc strain, freshly isolated from the symbiotic gland tissue of the angiosperm Gunnera manicata Linden, was analyzed and compared with the proteome of the same strain when free-living. Extracted proteins were separated by two-dimensional gel electrophoresis and were identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry combined with tandem mass spectrometry. Even when the higher percentage of differentiated cells (heterocysts) in symbiosis was compensated for, the majority of the proteins detected in the symbiotic cyanobacteria were present in the free-living counterpart, indicating that most cellular processes were common for both stages. However, differential expression profiling revealed a significant number of proteins to be down-regulated or missing in the symbiotic stage, while others were more abundant or only expressed in symbiosis. The differential protein expression was primarily connected to i) cell envelope-associated processes, including proteins involved in exopolysaccharide synthesis and surface and membrane associated proteins, ii) to changes in growth and metabolic activities (C and N), including upregulation of nitrogenase and proteins involved in the oxidative pentose phosphate pathway and downregu-lation of Calvin cycle enzymes, and iii) to the dark, micro-aerobic conditions offered inside the Gunnera gland cells, including changes in relative phycobiliprotein concentrations. This is the first comprehensive analysis of proteins in the symbiotic state.

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