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1.
J Immunol Methods ; 514: 113437, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36736950

RESUMEN

In Covid-19 and autoimmune patients, there are several similarities revealed in the immune responses (Liu et al., 2021; Woodruff et al., 2020). Earlier, we firstly detected a truncated (48 kDa) form of the unconventional Myosin 1C (48/Myo1C) in a fraction of proteins soluble in 10% 2,2,2-trichloroacetic acid (TCA). These proteins were obtained from blood serum of patients with autoimmune diseases, such as multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis (Kit et al., 2018). Here, we demonstrated that content of 48/Myo1C was also elevated in blood serum of the severe Covid-19 patients. Whereas in blood of 28 clinically healthy human individuals regularly tested for Covid-19 infection, the amount of this protein was undetectable or very low, in blood of 16 of 28 patients hospitalized with severe course of this disease, its amount was significantly increased. Dexamethasone, steroid hormone which is widely used for treatment of severe Covid-19 patients, induced time-dependent elevation of the 48/Myo1C in blood of such patients. The 48/Myo1C dose-dependently suppressed the viability of anti-CD3-activated lymphocytes of human peripheral blood. Recently, we used affinity chromatography on the magnetic poly(glycidyl-methacrylate) (mag-PGMA-NH2) microparticles functionalized with Myo1C and MALDI-TOF mass spectrometry with molecular modeling in silico in order to identify potential molecular partners of the 48/Myo1C. It was found that 48/Myo1C might bind to component 3 of the complement system and the anti-thrombin-III (Starykovych et al., 2021). Thus, the mechanisms of the pathogenic action of truncated form of Myo1C in severe COVID-19 patients may involve a suppression of the immune cells, as well as modulation of complement and coagulation cascades.


Asunto(s)
Enfermedades Autoinmunes , COVID-19 , Esclerosis Múltiple , Humanos , Miosina Tipo I/química , Miosina Tipo I/metabolismo , Suero/metabolismo , COVID-19/diagnóstico
2.
Front Plant Sci ; 13: 1009756, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36340352

RESUMEN

Soil lead (Pb) contamination is one of the environmental problems facing the modern world. Sources of Pb in soil include industrial activities such as mining and smelting processes, agricultural activities such as application of insecticide and municipal sewage sludges, and urban activities such as use of lead in gasoline, paints, and other materials. Phytoremediation is the direct use of living green plants and is an effective, cheap, non-invasive, and environmentally friendly technique used to transfer or stabilize all the toxic metals and environmental pollutants in polluted soil or groundwater. Current work in this area is invested in elucidating mechanisms that underpin toxic-metal tolerance and detoxification mechanisms. The present study aims to gain insight into the mechanisms of Pb tolerance in T. qataranse by comparative proteomics. MALDI-TOF/MS and in silico proteome analysis showed differential protein expression between treated (50 mg kg⎯1 Pb) and untreated (0 mg kg⎯1 Pb) T. qataranse. A total of eighty-six (86) differentially expressed proteins, most of which function in ion and protein binding, antioxidant activity, transport, and abiotic response stress, were identified. In addition, essential stress-regulating metabolic pathways, including glutathione metabolism, cellular response to stress, and regulation of HSF1-mediated heat shock response, were also enriched. Also, at 52- and 49-kDa MW band areas, up to six hypothetical proteins with unknown functions were identified. Of these, protein AXX17_AT2G26660 is highly rich in glycine amino acid residues (up to 76%), suggesting that it is a probable glycine-rich protein (GRP) member. Although GRPs are known to be involved in plant defense against abiotic stress, including salinity and drought, there is no report on their role on Pb tolerance and or detoxification in plants. Further enrichment analysis in the current study reveals that the hypothetical proteins do not interact with known proteins and are not part of any enriched pathway. However, additional research is needed to functionally validate the role of the identified proteins in Pb detoxification mechanism.

3.
Protein Pept Lett ; 29(5): 473-484, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35306981

RESUMEN

AIM: This study aims to identify novel post-translational modifications in human serum albumin by mass spectrometry. BACKGROUND: Serum albumin is the most abundant protein in plasma, has many physiological functions, and is in contact with most of the cells and tissues of the human body. Post-translational modifications (PTMs) may affect functions, stability, and localization of albumin. METHODS: Human serum albumin (HSA) was used for tryptic digestion in-solution or in-gel. Mass spectrometry was applied to identify PTMs in HSA. 3-dimensional modeling was applied to explore the potential impact of PTMs on known functions of albumin. RESULTS: Here, we report the identification of 61 novel PTMs of human serum albumin. Phosphorylation, glycosylation, nitrosylation, deamidation, methylation, acetylation, palmitoylation, geranylation, and farnesylation are some examples of the identified PTMs. Mass spectrometry was used for the identification of PTMs in a purified HSA and HSA from the human plasma. Threedimensional modeling of albumin with selected PTMs showed the location of these PTMs in the regions involved in albumin interactions with drugs, metals, and fatty acids. The location of PTMs in these regions may modify the binding capacity of albumin. CONCLUSION: This report adds 61 novel PTMs to the catalog of human albumin.


Asunto(s)
Procesamiento Proteico-Postraduccional , Albúmina Sérica Humana , Acetilación , Humanos , Espectrometría de Masas/métodos , Fosforilación , Albúmina Sérica/metabolismo , Albúmina Sérica Humana/química
4.
Curr Protein Pept Sci ; 23(2): 114-120, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35176988

RESUMEN

Post-translational modifications (PTMs) may affect the functions of human serum albumin. Here we review reports of novel PTMs of human serum albumin. This study reviewed one hundred twenty-three recently reported novel O-phosphorylation, glycation, methylation, carbonylation, and acetylation of albumin. Furthermore, the potential impact of these PTMs on albumin functions is discussed. Knowledge of these PTMs of albumin is important for the use of albumin in medical applications, e.g., in transfusion, drug formulations, and remedies.


Asunto(s)
Procesamiento Proteico-Postraduccional , Albúmina Sérica Humana , Acetilación , Humanos , Metilación , Fosforilación
5.
EJIFCC ; 33(4): 295-308, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36605305

RESUMEN

Purpose: Serum albumin is in contact with practically all cells in the human body, including tumor cells in cancer patients. The purpose of this study was to explore whether cancer cells affect post-translational modifications (PTMs) of albumin. Material and methods: Mass spectrometry was used to identify the PTMs. Purified human serum albumin was incubated with human breast cancer cells MDA-MB-231, MDA-MB-468, MCF7, or kept in water or in cell culture media. PTMs which were affected upon exposure of the albumin to cancer cells were identified. Three-dimensional analysis was performed to locate PTMs in albumin. Results: We report here that an exposure to human breast cancer cells affected post-translational modifications (PTMs) of 14 peptides of human serum albumin (HSA). PTMs at 8 peptides were observed upon exposure of HSA to metastatic MDA-MB-231 and MDA-MB-468 breast cancer cells. PTMs at another 6 peptides were lost in MDA-MB-231 and MDA-MB-468 cells, while these 6 PTMs were observed in HSA exposed to conditionally tumorigenic MCF7 cells, or in HSA kept in water or a cell culture medium. Cancer cell altered phosphorylation, deamidation followed by methylation, acetylation, myristylation, palmitoylation, methylation, cysteine persulfide, and S-6-FMN cysteine modifications were detected in HSA. These PTMs locate predominantly in IB and IIA domains of HSA. Three-dimensional analysis showed that this region corresponds to the lipid-binding site and Sudlow's site 1. Conclusion: Data reported here show that 14 PTMs of human serum albumin can be modified upon its exposure to human breast cancer cells.

6.
Mol Biol Rep ; 49(1): 587-594, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34731368

RESUMEN

DNA-dependent protein kinase catalytic subunit (DNA-PKcs) has emerged as a regulator of carcinogenesis. Increased expression of DNA-PKcs correlates with metastatic cancers. Here we review recently reported crosstalk of DNA-PKcs with estrogen (ER), progesterone (PR) and epidermal growth factor (EGFR) receptors. The reports show an extensive network of functional and direct interactions. Targeted studies focused on specific molecular mechanisms, and a systems biology network analysis shows unbiasedly engagement of various cellular functions. Feedforward regulation between expression and activities of DNA-PKcs and ER, DNA-PKcs-dependent phosphorylation of PR and an impact on PR-dependent transcription, and DNA-PKcs-promoted EGFR-dependent aggressiveness and metastases are examples of the results of targeted studies. Systems biology approach extracted many more genes and proteins engaged by DNA-PKcs in interaction with ER, PR, and EGFR. Examples are such regulators and predictors of breast tumorigenesis as BRCA1, TP53, and 18 genes of the MammaPrint signature. Reviewed here data suggest that the diagnostic value of DNA-PKcs in the context of ER, PR and EGFR signaling is defined by a network signature rather than by single markers. This review summarizes mechanisms of DNA-PKcs interaction with ER, PR, and EGFR, highlights tumor suppressors and oncogenes engaged by DNA-PKcs, and emphasizes the importance of diagnostic network-based signatures.


Asunto(s)
Proteína Quinasa Activada por ADN/metabolismo , Neoplasias/etiología , Neoplasias/metabolismo , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Animales , Biomarcadores , Susceptibilidad a Enfermedades , Regulación Neoplásica de la Expresión Génica , Genómica/métodos , Humanos , Neoplasias/patología , Neoplasias/terapia , Unión Proteica , Proteómica/métodos , Transducción de Señal
7.
Sci Rep ; 11(1): 5228, 2021 03 04.
Artículo en Inglés | MEDLINE | ID: mdl-33664395

RESUMEN

Clinical reports show that the management of cancer patients infected with SARS-CoV-2 requires modifications. Understanding of cancer-relevant mechanisms engaged by the virus is essential for the evidence-based management of cancer. The network of SARS-CoV-2 regulatory mechanisms was used to study potential engagement of oncogenes, tumor suppressors, other regulators of tumorigenesis and clinical markers used in the management of cancer patients. Our network analysis confirms links between COVID-19 and tumorigenesis that were predicted in epidemiological reports. The COVID-19 network shows the involvement of tumorigenesis regulators and clinical markers. Regulators of cell proliferation, death, migration, and the immune system were retrieved. Examples are pathways initiated by EGF, VEGF, TGFß and FGF. The SARS-CoV-2 network engages markers for diagnosis, prognosis and selection of treatment. Intersection with cancer diagnostic signatures supports a potential impact of the virus on tumorigenesis. Clinical observations show the diversity of symptoms correlating with biological processes and types of cells engaged by the virus, e.g. epithelial, endothelial, smooth muscle, glial and immune system cells. Our results describe an extensive engagement of cancer-relevant mechanisms and clinical markers by COVID-19. Engagement by the virus of clinical markers provides a rationale for clinical decisions based on these markers.


Asunto(s)
Biomarcadores de Tumor/metabolismo , COVID-19/metabolismo , Neoplasias/metabolismo , SARS-CoV-2/metabolismo , Carcinogénesis , Humanos , Neoplasias/complicaciones
8.
Reprod Biol ; 21(1): 100481, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33529998

RESUMEN

The dynamic embryo development during the early stages of gestation requires precise molecular changes, including proteomic ones. We aimed to find unique proteins for porcine conceptuses specifically during the peri-implantation period, i.e. on days 15-16 of pregnancy. The proteomic profile of these conceptuses was compared with conceptuses at an earlier stage of the development, i.e. collected during maternal recognition of pregnancy on days 12-13 of pregnancy. The 2DE, gel image analysis, and MALDI TOF mass spectrometry were used 500 protein spots were annotated as common to conceptuses harvested during both studied periods. Proteomic profile of the conceptuses collected during the peri-implantation period contains 24 unique proteins. Identified unique for the peri-implantation period proteins are involved in adhesion processes, cadherin, and actin-binding, and actin filament organization, extracellular matrix organization, and cytoskeleton organization. Systemic analysis of identified proteins confirmed their involvement in cell adhesion and cytoskeletal organization as being two major affected functions. The unique proteins might be recognized as factors conditioning the proper peri-implantation embryo development and gaining competences for implantation. In further studies, BRCA1 might be considered as a candidate for a potential marker of embryonic competences for implantation in pigs.


Asunto(s)
Embrión de Mamíferos/metabolismo , Desarrollo Embrionario/fisiología , Regulación del Desarrollo de la Expresión Génica/fisiología , Proteómica , Porcinos/embriología , Animales
9.
Biomed Chromatogr ; 35(4): e5029, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33201534

RESUMEN

We firstly identified 48 kDa molecular form of the unconventional myosin 1c (p48/Myo1C), and isolated it from blood serum of multiple sclerosis patients. The amount of p48/Myo1C in human blood serum correlated with some autoimmune, hemato-oncological and neurodegenerative diseases and thus may serve as a potential molecular biomarker. The biological functions of this protein in human blood remain unknown. Previously, we used the monodisperse magnetic poly (glycidyl methacrylate)(mag-PGMA-NH2 ) microspheres with immobilized 48/Myo1C and western-blot analysis, which allowed us to identify IgM and IgG immunoglobulins presenting an affinity to this protein. Here, we used mass spectrometry followed by the western blotting in order to identify other blood serum proteins with affinity to 48/Myo1C. The obtained data demonstrate that 48/Myo1C binds to component 3 of the complement and the antithrombin-III proteins. A combination of magnetic microparticle-based affinity chromatography with MALDI-TOF mass spectrometry and an in silico analysis provided an opportunity to identify the partners of interaction of 48/Myo1C with other proteins, in particular those participating in complement and coagulation cascades.


Asunto(s)
Proteínas Sanguíneas/análisis , Proteínas Sanguíneas/metabolismo , Cromatografía de Afinidad/métodos , Miosina Tipo I/metabolismo , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Proteínas Sanguíneas/química , Western Blotting , Humanos , Imanes , Microesferas , Modelos Moleculares , Esclerosis Múltiple/sangre , Miosina Tipo I/química , Pronóstico , Unión Proteica
10.
Biochem Biophys Res Commun ; 521(4): 1010-1016, 2020 01 22.
Artículo en Inglés | MEDLINE | ID: mdl-31727370

RESUMEN

Smad2 is a crucial component of intracellular signaling by transforming growth factor-ß (TGFß). Here we describe that Smad2 is glycosylated, which is a novel for Smad2 post-translational modification. We showed that the Smad2 glycosylation was inhibited upon treatment of cells with 17ß-estradiol, and was enhanced in cells in a dense culture as compared to cells in a sparse culture. The Smad2 glycosylation was not dependent on the C-terminal phosphorylation of Smad2, and was not affected by TGFß1 treatment of the cells. Smad2 was glycosylated at multiple sites, and one of the predicted sites is Serine110. Thus, Smad2 is glycosylated, and this post-translational modification was modulated by 17ß-estradiol but not by TGFß1.


Asunto(s)
Procesamiento Proteico-Postraduccional , Proteína Smad2/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Alanina/genética , Animales , Células CHO , Recuento de Células , Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Concanavalina A/farmacología , Cricetinae , Cricetulus , Estradiol/farmacología , Glicosilación , Humanos , Lectinas/farmacología , Células MCF-7 , Mutación/genética , Lectinas de Plantas/farmacología , Procesamiento Proteico-Postraduccional/efectos de los fármacos , Transporte de Proteínas/efectos de los fármacos , Serina/genética
11.
Cancer Genomics Proteomics ; 16(6): 505-518, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31659104

RESUMEN

BACKGROUND/AIM: Proteomics of invasiveness opens a window on the complexity of the metastasis-engaged mechanisms. The extend and types of this complexity require elucidation. MATERIALS AND METHODS: Proteomics, immunohistochemistry, immunoblotting, network analysis and systems cancer biology were used to analyse acquisition of invasiveness by human breast adenocarcinoma cells. RESULTS: We report here that invasiveness network highlighted the involvement of hallmarks such as cell proliferation, migration, cell death, genome stability, immune system regulation and metabolism. Identified involvement of cell-virus interaction and gene silencing are potentially novel cancer mechanisms. Identified 6,113 nodes with 11,055 edges affecting 1,085 biological processes show extensive re-arrangements in cell physiology. These high numbers are in line with a similar broadness of networks built with diagnostic signatures approved for clinical use. CONCLUSION: Our data emphasize a broad systemic regulation of invasiveness, and describe the network of this regulation.


Asunto(s)
Adenocarcinoma , Regulación Neoplásica de la Expresión Génica , Inestabilidad Genómica , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Femenino , Humanos , Células MCF-7 , Invasividad Neoplásica
12.
Biomed Chromatogr ; 33(11): e4647, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31299101

RESUMEN

The cytopoxic effect of RL2 lactaptin (the recombinant analog of proteolytic fragment of human kappa-casein) toward tumor cells in vitro and in vivo presents it as a novel promising antitumor drug. The binding of any drug with serum proteins can affect their activity, distribution, rate of excretion and toxicity in the human body. Here, we studied the ability of RL2 to bind to various blood serum proteins. Using magnetic microparticles bearing by RL2 as an affinity matrix, in combination with mass spectrometry and western blot analysis, we found a number of blood serum proteins possessing affinity for RL2. Among them IgA, IgM and IgG subclasses of immunoglobulins, apolipoprotein A1 and various cortactin isoforms were identified. This data suggests that in the bloodstream RL2 lactaptin takes part in complicate protein-protein interactions, which can affect its activity.


Asunto(s)
Antineoplásicos/metabolismo , Proteínas Sanguíneas/aislamiento & purificación , Proteínas Sanguíneas/metabolismo , Caseínas/metabolismo , Imanes/química , Proteínas Sanguíneas/análisis , Cromatografía de Afinidad/métodos , Humanos , Microesferas , Ácidos Polimetacrílicos/química , Proteínas Recombinantes/metabolismo , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos
13.
Int J Mol Med ; 42(3): 1615-1624, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29956719

RESUMEN

Epidermal growth factor (EGF) and estrogen are potent regulators of breast tumorigenesis. Their short­term actions on human breast epithelial cells have been investigated extensively. However, the consequence of a long­term exposure to EGF and estrogen remains to be fully elucidated. The present study examined the effects of long­term exposure to EGF and 17ß­estradiol on the proliferation, transformation, expression of markers of stemness, and tumorigenesis of MCF7 human breast adenocarcinoma cells. Exposure to EGF and/or 17ß­estradiol irreversibly enhanced the proliferation rate of MCF7 cells, even following withdrawal. However, in a mouse xenograft experiment, no significant difference in tumor volume was observed between tumors derived from cells exposed to EGF, 17ß­estradiol or EGF + 17ß­estradiol. Immunohistochemistry performed on tumors derived from 17ß­estradiol­exposed cells revealed reduced cell proliferation and vessel scores, according to the results obtained using Ki67 and von Willebrand factor staining, respectively. The EGF­ and/or 17ß­estradiol­treated cells exhibited an increased ratio of cluster of differentiation (CD)44+/CD24­ cells and enhanced ability to form mammospheres. Furthermore, the long­term exposure of MCF7 cells to EGF and 17ß­estradiol altered their responsiveness to short­term stimulatory or inhibitory treatments with EGF, 17ß­estradiol, transforming growth factor­ß1 (TGFß1), Iressa and SB431542. Therefore, the findings indicated that sustained exposure of MCF7 cells to EGF and/or 17ß­estradiol resulted in enhanced cell proliferation and mammosphere formation, an increased ratio of CD44+/CD24­ cells, and altered responses to short­term treatments with EGF, 17ß­estradiol, TGFß1, and drugs inhibiting these signaling pathways. However, this sustained exposure was not sufficient to affect tumor take or volume in a xenograft mouse model.


Asunto(s)
Transformación Celular Neoplásica/patología , Factor de Crecimiento Epidérmico/farmacología , Estradiol/farmacología , Ensayos Antitumor por Modelo de Xenoinjerto , Animales , Benzamidas/farmacología , Carcinogénesis/efectos de los fármacos , Carcinogénesis/patología , Proliferación Celular/efectos de los fármacos , Transformación Celular Neoplásica/efectos de los fármacos , Transformación Celular Neoplásica/metabolismo , Dioxoles/farmacología , Femenino , Gefitinib , Humanos , Células MCF-7 , Ratones SCID , Modelos Biológicos , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Fenotipo , Quinazolinas/farmacología , Esferoides Celulares/efectos de los fármacos , Esferoides Celulares/metabolismo , Esferoides Celulares/patología , Tamoxifeno/farmacología
14.
Pathobiology ; 85(4): 211-219, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29617697

RESUMEN

OBJECTIVE: The aim of this study was to identify differences in proteome profiles of diffuse large B-cell lymphoma (DLBCL) of nongerminal center (non-GC) versus GC type in the search for new markers and drug targets. METHODS: Six DLBCL, with 3 repeats for each, were used for the initial study by proteomics: 3 non-GC and 3 GC DLBCL cases. For immunohistochemistry, tissue microarrays were made from 31 DLBCL samples: 16 non-GC de novo lymphomas and 15 GC cases (11 transformed from follicular lymphomas and 4 de novo GC lymphomas). Proteome profiling was performed by two-dimensional gel electrophoresis and MALDI-TOF mass spectrometry. RESULTS: Ninety-one proteins were found differentially expressed in non-GC compared to GC type. The Cytoscape tool was used for systemic analysis of proteomics data, revealing 19 subnetworks representing functions affected in non-GC versus GC types of DLBCL. CONCLUSION: A validation study of 3 selected proteins (BiP/Grp78, Hsp90, and cyclin B2) showed the enhanced expression in non-GC DLBCL, supporting the proteomics data.


Asunto(s)
Biomarcadores de Tumor/análisis , Linfoma de Células B Grandes Difuso , Adulto , Anciano , Anciano de 80 o más Años , Preescolar , Chaperón BiP del Retículo Endoplásmico , Femenino , Perfilación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Proteómica
15.
Reprod Fertil Dev ; 29(11): 2255-2268, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28416050

RESUMEN

Reproductive processes in domestic pigs have been studied extensively. Pigs are one of the main sources of meat for human consumption and are an established model for investigations into mammalian, including human, reproductive physiology. Studies of the uterus during early pregnancy will lead to a better understanding of mechanisms governing pregnancy. Proteomics provides the possibility to explore endometrial functions in an unbiased way. The aim of the study was to compare endometrium harvested from Days 12-13 and 15-16 of pregnancy with the corresponding days of the oestrous cycle. We identified endometrial proteins that are unique to the early stages of pregnancy (Days 12-13 and 15-16). Twenty-one proteins were identified that were uniquely expressed on the selected days of pregnancy or the oestrous cycle. Out of 21 identified proteins, 14 referred to the pregnancy periods. Systemic analysis of the identified proteins revealed cell adhesion and cytoskeletal organisation as two of the major functions, both of which are important for the establishment and maintenance of pregnancy. Thrombospondin 1 expression was validated using western blotting analysis and the results suggest its involvement in the adhesiveness of the embryo during the peri-implantation period in pigs.


Asunto(s)
Implantación del Embrión/fisiología , Endometrio/metabolismo , Preñez/metabolismo , Animales , Femenino , Embarazo , Proteómica , Porcinos
16.
Protein Pept Lett ; 23(9): 808-11, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27338077

RESUMEN

Monitoring of multiple sclerosis (MS) requires additional molecular markers. Recently, we used original TCA-precipitation/extraction approach in combination with MALDI TOF/TOF mass-spectrometry and identified earlier unknown 48 kDa form of the unconventional myosin IC isoform b (Myo1C) in blood serum of the MS patients. Further examination of TCA-extracted fraction of blood serum of these patients by means of thin-layer chromatography and HPLC gel-filtration allowed detecting 300-500 Da peptides. MALDI TOF/TOF massspectrometry of these peptides showed that they contain Ser-Pro-Cys amino acid sequence. We discussed potential mechanisms of a release of these peptides that were earlier unknown in blood serum of the MS patients.


Asunto(s)
Cisteína/metabolismo , Esclerosis Múltiple/metabolismo , Péptidos/sangre , Prolina/metabolismo , Serina/metabolismo , Adulto , Secuencia de Aminoácidos , Biomarcadores/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Péptidos/química , Péptidos/aislamiento & purificación , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Espectrometría de Masas en Tándem , Adulto Joven
17.
Biochem Biophys Rep ; 5: 175-179, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28955821

RESUMEN

We searched for protein markers present in blood serum of multiple sclerosis (MS), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) patients in comparison to healthy human individuals. We used precipitation/extraction methods and MALDI TOF/TOF mass spectrometry, and identified a protein with Mr ~46 kDa as a fragment of human unconventional myosin IC isoform b (Myo1C). Western blotting with specific anti-human Myo1C antibodies confirmed the identity. Screening of blood serum samples from different autoimmune patients for the presence of Myo1c revealed its high level in MS and RA patients, relatively low level in SLE patients, and undetected in healthy donors. These data are suggesting that the level of p46 Myo1C in blood serum is a potential marker for testing of autoimmune diseases.

18.
Cancer Metastasis Rev ; 34(4): 611-8, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26328523

RESUMEN

BRMS1 was discovered over a decade ago as a potential tumor suppressor gene. In this review, we summarize the recent findings about the structure of BRMS1, mechanisms of its action and a role of BRMS1 in the cancer progression. As a suppressor of metastasis, BRMS1 has demonstrated a variety of ways to act on the cell functions, such as cell migration, invasiveness, angiogenesis, cell survival, cytoskeleton rearrangements, cell adhesion, and immune recognition. This variety of effects is a likely reason behind the robustness of anti-metastatic influence of BRMS1. Intracellular signaling mechanisms employed by BRMS1 include regulation of transcription, EGF/HER2 signaling, and expression of NF-kB, fascin, osteopontin, and IL-6. Recently reported clinical studies confirm that BRMS1 can indeed be used as a prognostic marker. Approaches to employ BRMS1 in a development of anti-cancer treatment have also been made. The studies reviewed here with respect to BRMS1 structure, cellular effects, intracellular signaling, and clinical value consolidate the importance of BRMS1 in the development of metastasis.


Asunto(s)
Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Metástasis de la Neoplasia/patología , Proteínas de Neoplasias/genética , Proteínas Represoras/genética , Biomarcadores de Tumor/genética , Adhesión Celular/genética , Movimiento Celular/genética , Supervivencia Celular/genética , Progresión de la Enfermedad , Femenino , Genes Supresores de Tumor , Humanos , Invasividad Neoplásica/genética , Metástasis de la Neoplasia/genética , Neovascularización Patológica/genética
19.
J Invest Dermatol ; 135(2): 400-410, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25207817

RESUMEN

In this study, we used proteomics and biological network analysis to evaluate the potential biological processes and components present in the identified proteins of biopsies from cutaneous leishmaniasis (CL) patients infected by Leishmania braziliensis in comparison with normal skin. We identified 59 proteins differently expressed in samples from infected and normal skin. Biological network analysis employing identified proteins showed the presence of networks that may be involved in the cell death mediated by cytotoxic T lymphocytes. After immunohistochemical analyses, the expression of caspase-9, caspase-3, and granzyme B was validated in the tissue and positively correlated with the lesion size in CL patients. In conclusion, this work identified differentially expressed proteins in the inflammatory site of CL, revealed enhanced expression of caspase-9, and highlighted mechanisms associated with the progression of tissue damage observed in lesions.


Asunto(s)
Leishmaniasis Cutánea/metabolismo , Proteoma , Caspasa 3/análisis , Caspasa 9/análisis , Granzimas/análisis , Humanos , Inmunohistoquímica , Leishmaniasis Cutánea/patología , Piel/patología
20.
Biochem Biophys Res Commun ; 454(1): 202-9, 2014 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-25450381

RESUMEN

Neuroblastoma develops through processes which include cellular dedifferentiation. Ability of tumors to form spheroids is one of the manifestations of dedifferentiation and carcinogenic transformation. To study mechanisms of dedifferentiation of neuroblastoma cells, we generated spheroids and performed a proteomics study to compare the spheroids with parental SK-N-BE2 cells. We observed that dedifferentiation induced extensive changes in the proteome profiles of the cells, which affected more than 30% of detected cellular proteins. Using mass spectrometry, we identified 239 proteins affected by dedifferentiation into spheroids as compared to the parental cells. These proteins represented such regulatory processes as transcription, cell cycle regulation, apoptosis, cell adhesion, metabolism, intracellular transport, stress response, and angiogenesis. A number of potent regulators of stemness, differentiation and cancer were detected as subnetworks formed by the identified proteins. Our validation tissue microarray study of 30 neuroblastoma cases confirmed that two of the identified proteins, DISC1 and DNA-PKcs, had their expression increased in advanced malignancies. Thus, our report unveiled extensive changes of the cellular proteome upon dedifferentiation of neuroblastoma cells, indicated top subnetworks and clusters of molecular mechanisms involved in dedifferentiation, and provided candidate biomarkers for clinical studies.


Asunto(s)
Desdiferenciación Celular/fisiología , Proteínas de Neoplasias/metabolismo , Neuroblastoma/metabolismo , Neuroblastoma/patología , Proteoma/metabolismo , Biomarcadores de Tumor/metabolismo , Línea Celular Tumoral , Proteína Quinasa Activada por ADN/metabolismo , Humanos , Espectrometría de Masas , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Proteínas del Tejido Nervioso/metabolismo , Células-Madre Neurales/metabolismo , Células-Madre Neurales/patología , Proteínas Nucleares/metabolismo , Mapas de Interacción de Proteínas , Proteómica , Esferoides Celulares/metabolismo , Esferoides Celulares/patología , Análisis de Matrices Tisulares
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