47 results on '"Bzowska, Monika"'
Search Results
2. Pro-inflammatory properties of aureocin A53
- Author
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Śmiałek-Bartyzel, Justyna, Bzowska, Monika, and Mak, Paweł
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- 2024
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- View/download PDF
3. Glutathione-modified hyaluronic acid nanoparticles for the targeted delivery of sulfasalazine to neuroblastoma
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Kasprzyk, Martyna, Hinz, Alicja, Bzowska, Monika, Lachowicz, Dorota, Wolski, Karol, and Karewicz, Anna
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- 2024
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4. BacSp222 bacteriocin as a novel ligand for TLR2/TLR6 heterodimer
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Śmiałek-Bartyzel, Justyna, Bzowska, Monika, Mężyk-Kopeć, Renata, Kwissa, Marcin, and Mak, Paweł
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- 2023
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5. In vitro/ex vivo evaluation of multifunctional collagen/chitosan/hyaluronic acid hydrogel-based alendronate delivery systems
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Klara, Joanna, Hinz, Alicja, Bzowska, Monika, Horak, Wojciech, and Lewandowska-Łańcucka, Joanna
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- 2024
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- View/download PDF
6. Stabilization of liposomes with silicone layer improves their elastomechanical properties while not compromising biological features
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Karabasz, Alicja, Szuwarzyński, Michał, Nowakowska, Maria, Bzowska, Monika, and Lewandowska-Łańcucka, Joanna
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- 2020
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7. Mouse IgG3 binding to macrophage-like cells is prevented by deglycosylation of the antibody or by Accutase treatment of the cells
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Karabasz, Alicja, Bzowska, Monika, Bereta, Joanna, Czarnek, Maria, Sochalska, Maja, and Klaus, Tomasz
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- 2021
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8. Blood-compatible, stable micelles of sodium alginate – Curcumin bioconjugate for anti-cancer applications
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Lachowicz, Dorota, Karabasz, Alicja, Bzowska, Monika, Szuwarzyński, Michał, Karewicz, Anna, and Nowakowska, Maria
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- 2019
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9. Encapsulation of camptothecin into pegylated polyelectrolyte nanocarriers
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Bzowska, Monika, Karabasz, Alicja, and Szczepanowicz, Krzysztof
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- 2018
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10. Pegylated polyelectrolyte nanoparticles containing paclitaxel as a promising candidate for drug carriers for passive targeting
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Szczepanowicz, Krzysztof, Bzowska, Monika, Kruk, Tomasz, Karabasz, Alicja, Bereta, Joanna, and Warszynski, Piotr
- Published
- 2016
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11. Bacteriocin BacSp222 and Its Succinylated Forms Exhibit Proinflammatory Activities Toward Innate Immune Cells
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ÅmiaÅek,Justyna, Bzowska,Monika, Hinz,Alicja, MÄżyk-KopeÄ,Renata, SoÅtys,Kamilla, and Mak,PaweÅ
- Subjects
Journal of Inflammation Research - Abstract
Justyna Śmiałek,1,* Monika Bzowska,2,* Alicja Hinz,2 Renata Mężyk-Kopeć,2 Kamilla Sołtys,2 Paweł Mak1 1Department of Analytical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland; 2Department of Cell Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland*These authors contributed equally to this workCorrespondence: Paweł Mak, Department of Analytical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7 St., Kraków, 30-387, Poland, Tel +48 12 664 6511, Fax +48 12 664 6902, Email pawel.mak@uj.edu.plPurpose: The zoonotic opportunistic pathogen Staphylococcus pseudintermedius 222 produces BacSp222 â an atypical peptide exhibiting the features of a bacteriocin, a virulence factor, and a molecule modulating the host inflammatory reaction. The peptide is secreted in an unmodified form and, additionally, two forms modified posttranslationally by succinylation. This study is a comprehensive report focusing on the proinflammatory properties of such molecules.Methods: The study was performed on mouse monocyte/macrophage-like and endothelial cell lines as well as human neutrophils. The following peptides were studied: BacSp222, its succinylated forms, the form deprived of formylated methionine, and a reference bacteriocin â nisin. The measurements of the nitric oxide (NO) level, induced NO synthase (iNOS) expression, the profile of secreted cytokines, NF-kappa-B activation, reactive oxygen species (ROS) biosynthesis, and the formation of extracellular traps were conducted to evaluate the proinflammatory activity of the studied peptides.Results: BacSp222 and its succinylated forms effectively induced NO production and iNOS expression when combined with IFN-gamma in macrophage-like cells. All natural BacSp222 forms used alone or with IFN-gamma stimulated the production of TNF-alpha, MCP-1, and IL-1-alpha, while the co-stimulation with IFN-gamma increased IL-10 and IL-27. Upregulated TNF-alpha secretion observed after BacSp222 exposition resulted from increased expression but not from membrane TNF-alpha proteolysis. In neutrophils, all forms of bacteriocin upregulated IL-8, but did not induce ROS production or NETs formation. In all experiments, the activities of deformylated bacteriocin were lower or unequivocal in comparison to other forms of the peptide.Conclusion: All naturally secreted forms of BacSp222 exhibit proinflammatory activity against monocyte-macrophage cells and neutrophils, confirming that the biological role of BacSp222 goes beyond bactericidal and cytotoxic effects. The atypical posttranslational modification (succinylation) does not diminish its immunomodulatory activity in contrast to the lower antibacterial potential or cytotoxicity of such modified form established in previous studies.Keywords: cytokines, neutrophils, NF-kappa-B activation, nisin, nitric oxide, posttranslational modifications, Staphylococcus pseudintermedius 222
- Published
- 2022
12. Cytotoxic activity of paclitaxel incorporated into polyelectrolyte nanocapsules
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Karabasz, Alicja, Bzowska, Monika, Łukasiewicz, Sylwia, Bereta, Joanna, and Szczepanowicz, Krzysztof
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- 2014
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13. Bacteriocin BacSp222 and Its Succinylated Forms Exhibit Proinflammatory Activities Toward Innate Immune Cells .
- Author
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Śmiałek, Justyna, Bzowska, Monika, Hinz, Alicja, Mężyk-Kopeć, Renata, Sołtys, Kamilla, and Mak, Paweł
- Subjects
PEPTIDES ,POST-translational modification ,NITRIC oxide ,NITRIC-oxide synthases ,REACTIVE oxygen species ,TUMOR necrosis factors ,MICROCOCCACEAE - Abstract
Purpose: The zoonotic opportunistic pathogen Staphylococcus pseudintermedius 222 produces BacSp222 – an atypical peptide exhibiting the features of a bacteriocin, a virulence factor, and a molecule modulating the host inflammatory reaction. The peptide is secreted in an unmodified form and, additionally, two forms modified posttranslationally by succinylation. This study is a comprehensive report focusing on the proinflammatory properties of such molecules. Methods: The study was performed on mouse monocyte/macrophage-like and endothelial cell lines as well as human neutrophils. The following peptides were studied: BacSp222, its succinylated forms, the form deprived of formylated methionine, and a reference bacteriocin – nisin. The measurements of the nitric oxide (NO) level, induced NO synthase (iNOS) expression, the profile of secreted cytokines, NF-kappa-B activation, reactive oxygen species (ROS) biosynthesis, and the formation of extracellular traps were conducted to evaluate the proinflammatory activity of the studied peptides. Results: BacSp222 and its succinylated forms effectively induced NO production and iNOS expression when combined with IFN-gamma in macrophage-like cells. All natural BacSp222 forms used alone or with IFN-gamma stimulated the production of TNF-alpha, MCP-1, and IL-1-alpha, while the co-stimulation with IFN-gamma increased IL-10 and IL-27. Upregulated TNF-alpha secretion observed after BacSp222 exposition resulted from increased expression but not from membrane TNF-alpha proteolysis. In neutrophils, all forms of bacteriocin upregulated IL-8, but did not induce ROS production or NETs formation. In all experiments, the activities of deformylated bacteriocin were lower or unequivocal in comparison to other forms of the peptide. Conclusion: All naturally secreted forms of BacSp222 exhibit proinflammatory activity against monocyte-macrophage cells and neutrophils, confirming that the biological role of BacSp222 goes beyond bactericidal and cytotoxic effects. The atypical posttranslational modification (succinylation) does not diminish its immunomodulatory activity in contrast to the lower antibacterial potential or cytotoxicity of such modified form established in previous studies. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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14. Biomedical Applications of Multifunctional Polymeric Nanocarriers: A Review of Current Literature
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Karabasz,Alicja, Bzowska,Monika, and Szczepanowicz,Krzysztof
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International Journal of Nanomedicine - Abstract
Alicja Karabasz,1 Monika Bzowska,1 Krzysztof Szczepanowicz2 1Department of Cell Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland; 2Jerzy Haber Institute of Catalysis and Surface Chemistry, Polish Academy of Sciences, Kraków, PolandCorrespondence: Monika BzowskaDepartment of Cell Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 7 Gronostajowa Street, Kraków 30-387, PolandTel/Fax +48 12 664 63 88Email monika.bzowska@uj.edu.plKrzysztof SzczepanowiczJerzy Haber Institute of Catalysis and Surface Chemistry, Polish Academy of Sciences, 8 Niezapominajek Street, Kraków 30-239, PolandTel/Fax +48 12 639 51 21Email ncszczep@cyf-kr.edu.plAbstract: Polymeric nanomaterials have become a prominent area of research in the field of drug delivery. Their application in nanomedicine can improve bioavailability, pharmacokinetics, and, therefore, the effectiveness of various therapeutics or contrast agents. There are many studies for developing new polymeric nanocarriers; however, their clinical application is somewhat limited. In this review, we present new complex and multifunctional polymeric nanocarriers as promising and innovative diagnostic or therapeutic systems. Their multifunctionality, resulting from the unique chemical and biological properties of the polymers used, ensures better delivery, and a controlled, sequential release of many different therapeutics to the diseased tissue. We present a brief introduction of the classical formulation techniques and describe examples of multifunctional nanocarriers, whose biological assessment has been carried out at least in vitro. Most of them, however, also underwent evaluation in vivo on animal models. Selected polymeric nanocarriers were grouped depending on their medical application: anti-cancer drug nanocarriers, nanomaterials delivering compounds for cancer immunotherapy or regenerative medicine, components of vaccines nanomaterials used for topical application, and lifestyle diseases, ie, diabetes.Keywords: polymeric nanocarriers, biomedical application, anti-cancer, cancer immunotherapy, modern vaccines, regenerative medicine, lifestyle diseases – diabetes
- Published
- 2020
15. Fluorophore Localization Determines the Results of Biodistribution of Core-Shell Nanocarriers.
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Hinz, Alicja, Szczęch, Marta, Szczepanowicz, Krzysztof, and Bzowska, Monika
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- 2022
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16. Identification of ADAM10 as a major TNF sheddase in ADAM17-deficient fibroblasts
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Mężyk-Kopeć, Renata, Bzowska, Monika, Stalińska, Krystyna, Chełmicki, Tomasz, Podkalicki, Michał, Jucha, Jarosław, Kowalczyk, Katarzyna, Mak, Paweł, and Bereta, Joanna
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- 2009
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17. Addressing the Osteoporosis ProblemMultifunctional Injectable Hybrid Materials for Controlling Local Bone Tissue Remodeling.
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Gilarska, Adriana, Hinz, Alicja, Bzowska, Monika, Dyduch, Grzegorz, Kamiński, Kamil, Nowakowska, Maria, and Lewandowska-Łańcucka, Joanna
- Published
- 2021
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18. Comparison of various selection strategies used for isolation of human monoclonal scFv antibody specific to GPCRs heteromers
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Łukasiewicz, Sylwia, Stachowicz, Agata, Bzowska, Monika, and Dziedzicka-Wasylewska, Marta
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hetromer ,phage display ,biopanning ,scFv antibody ,GPCRs - Published
- 2019
19. Analysis of toxicity and anticancer activity of micelles of sodium alginate-curcumin
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Karabasz,Alicja, Lachowicz,Dorota, Karewicz,Anna, Mezyk-Kopec,Renata, StaliÅska,Krystyna, Werner,Ewa, Cierniak,Agnieszka, Dyduch,Grzegorz, Bereta,Joanna, and Bzowska,Monika
- Subjects
International Journal of Nanomedicine - Abstract
Alicja Karabasz1, Dorota Lachowicz2, Anna Karewicz3, Renata Mezyk-Kopec1, Krystyna StaliÅska1, Ewa Werner4,5, Agnieszka Cierniak6, Grzegorz Dyduch7, Joanna Bereta1, Monika Bzowska1 1Department of Cell Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland; 2Academic Centre for Materials and Nanotechnology, AGH University of Science and Technology, Kraków, Poland; 3Faculty of Chemistry, Jagiellonian University, Kraków, Poland; 4Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland; 5Department of Animal Reproduction and Anatomy, Faculty of Animal Science, University of Agriculture, Krakow, Poland; 6Department of General Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland; 7Department of Pathomorphology, Jagiellonian University Medical College, Kraków, PolandCorrespondence: Monika BzowskaJagiellonian University in Kraków, Faculty of Biochemistry, Biophysics and Biotechnology, Department of Cell Biochemistry, 7 Gronostajowa St., Kraków 30-387, PolandTel +48 12 664 6388Fax +48 12 664 6388Email monika.bzowska@uj.edu.plBackground: Curcumin is a natural polyphenol with anti-inflammatory, chemopreventive and anticancer activity. However, its high hydrophobicity and poor bioavailability limit its medical application. The development of nanocarriers for curcumin delivery is an attractive approach to overcome its low bioavailability and fast metabolism in the liver. We synthesized a blood compatible alginate-curcumin conjugate, AA-Cur, which formed colloidally stable micelles of approximately 200 nm and, as previously shown, exerted strong cytotoxicity against mouse cancer cell lines. Here we analyze in vivo toxicity and antitumor activity of AA-Cur in two different mouse tumor models.Method: Potential toxicity of intravenously injected AA-Cur was evaluated by: i) analyses of blood parameters (morphology and biochemistry), ii) histology, iii) DNA integrity (comet assay), and iv) cytokine profiling (flow cytometry). Antitumor activity of AA-Cur was evaluated by measuring the growth of subcutaneously inoculated colon MC38-CEA- or orthotopically injected breast 4T1 tumor cells in control mice vs mice treated with AA-Cur.Results: Injections of four doses of AA-Cur did not reveal any toxicity of the conjugate, thus indicating the safety of its use. AA-Cur elicited moderate anti-tumor activity toward colon MC38-CEA or breast 4T1 carcinomas.Conclusion: The tested conjugate of alginate and curcumin, AA-Cur, is non-toxic and safe, but exhibits limited anticancer activity.Keywords: curcumin, alginate conjugates, in vivo toxicity, antitumor activity
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- 2019
20. Effects of elastase and cathepsin G on the levels of membrane and soluble TNFα
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Mężyk-Kopeć, Renata, Bzowska, Malgorzata, Bzowska, Monika, Mickowska, Barbara, Mak, Pawel, Potempa, Jan, and Bereta, Joanna
- Published
- 2005
21. Tumour necrosis factor-α stimulates expression of TNF-α converting enzyme in endothelial cells
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Bzowska, Monika, Jura, Natalia, Lassak, Adam, Black, Roy A., and Bereta, Joanna
- Published
- 2004
22. The role of water in the confinement of ibuprofen in SBA-15.
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Gackowski, Mariusz, Ruggiero-Mikołajczyk, Małgorzata, Duraczyńska, Dorota, Hinz, Alicja, Bzowska, Monika, and Szczepanowicz, Krzysztof
- Abstract
The introduction of ibuprofen into mesopores of SBA-15 has been accomplished using the melting method. Samples exhibit from 9 to 33% of the hydrophobic drug. They are not toxic to mouse monocyte-macrophage cells and do not stimulate a pro-inflammatory response. The sample with 25% of the drug showed no crystalline ibuprofen and almost filled the mesopores, while the sample with 33% showed a total filling of the mesopores with some crystalline ibuprofen present. By means of 1D (
1 H,13 C HPDEC,13 C CP MAS) and 2D (1 H–1 H NOESY) MAS NMR spectroscopy, it has been shown that water coexists with ibuprofen in mesopores and has an impact on the mobility of ibuprofen molecules and their location within the sample (outside or inside mesopores). Studies in the dehydrated state show for the first time that the high mobility of ibuprofen in mesopores is directly connected to the presence of water. Dehydrated samples show slightly slower release rates in comparison to their hydrated counterparts. [ABSTRACT FROM AUTHOR]- Published
- 2021
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23. In vivo Studies on Pharmacokinetics, Toxicity and Immunogenicity of Polyelectrolyte Nanocapsules Functionalized with Two Different Polymers: Poly-L-Glutamic Acid or PEG.
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Karabasz, Alicja, Szczepanowicz, Krzysztof, Cierniak, Agnieszka, Mezyk-Kopec, Renata, Dyduch, Grzegorz, Szczęch, Marta, Bereta, Joanna, and Bzowska, Monika
- Published
- 2019
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24. Analysis of toxicity and anticancer activity of micelles of sodium alginate-curcumin.
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Karabasz, Alicja, Lachowicz, Dorota, Karewicz, Anna, Mezyk-Kopec, Renata, Stalińska, Krystyna, Werner, Ewa, Cierniak, Agnieszka, Dyduch, Grzegorz, Bereta, Joanna, and Bzowska, Monika
- Published
- 2019
- Full Text
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25. In vitro toxicity studies of biodegradable, polyelectrolyte nanocapsules.
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Karabasz, Alicja, Szczepanowicz, Krzysztof, Cierniak, Agnieszka, Bereta, Joanna, and Bzowska, Monika
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- 2018
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26. Tumour necrosis $factor‐\alpha$ stimulates expression of $TNF‐\alpha$ converting enzyme in endothelial cells
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Bzowska, Monika, Jura, Natalia, Lassak, Adam, Black, Roy A., and Bereta, Joanna
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ADAM17 ,TNF-R (p55) ,ectodomain shedding ,$TNF-\alpha$ ,cytokines - Published
- 2004
27. Structural and functional probing of PorZ, an essential bacterial surface component of the type-IX secretion system of human oral-microbiomic Porphyromonas gingivalis.
- Author
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Lasica, Anna M., Goulas, Theodoros, Mizgalska, Danuta, Zhou, Xiaoyan, de Diego, Iñaki, Ksiazek, Mirosław, Madej, Mariusz, Guo, Yonghua, Guevara, Tibisay, Nowak, Magdalena, Potempa, Barbara, Goel, Apoorv, Sztukowska, Maryta, Prabhakar, Apurva T., Bzowska, Monika, Widziolek, Magdalena, Thøgersen, Ida B., Enghild, Jan J., Simonian, Mary, Kulczyk, Arkadiusz W., Nguyen, Ky-Anh, Potempa, Jan, and Gomis-Rüth, F. Xavier
- Abstract
Porphyromonas gingivalis is a member of the human oral microbiome abundant in dysbiosis and implicated in the pathogenesis of periodontal (gum) disease. It employs a newly described type-IX secretion system (T9SS) for secretion of virulence factors. Cargo proteins destined for secretion through T9SS carry a recognition signal in the conserved C-terminal domain (CTD), which is removed by sortase PorU during translocation. Here, we identified a novel component of T9SS, PorZ, which is essential for surface exposure of PorU and posttranslational modification of T9SS cargo proteins. These include maturation of enzyme precursors, CTD removal and attachment of anionic lipopolysaccharide for anchorage in the outer membrane. The crystal structure of PorZ revealed two β-propeller domains and a C-terminal β-sandwich domain, which conforms to the canonical CTD architecture. We further documented that PorZ is itself transported to the cell surface via T9SS as a full-length protein with its CTD intact, independently of the presence or activity of PorU. Taken together, our results shed light on the architecture and possible function of a novel component of the T9SS. Knowledge of how T9SS operates will contribute to our understanding of protein secretion as part of host-microbiome interactions by dysbiotic members of the human oral cavity.
- Published
- 2016
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28. ADAM17 Silencing in Mouse Colon Carcinoma Cells: The Effect on Tumoricidal Cytokines and Angiogenesis.
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Das, Sudipta, Czarnek, Maria, Bzowska, Monika, Mężyk-Kopeć, Renata, Stalińska, Krystyna, Wyroba, Barbara, Sroka, Jolanta, Jucha, Jarosław, Deneka, Dawid, Stokłosa, Paulina, Ogonek, Justyna, Swartz, Melody A., Madeja, Zbigniew, and Bereta, Joanna
- Subjects
GENE silencing ,NEOVASCULARIZATION ,CELL proliferation ,PEPTIDES ,CYTOKINES ,ONCOLOGY - Abstract
ADAM17 (a disintegrin and metalloprotease 17) is a major sheddase for numerous growth factors, cytokines, receptors, and cell adhesion molecules and is often overexpressed in malignant cells. It is generally accepted that ADAM17 promotes tumor development via activating growth factors from the EGF family, thus facilitating autocrine stimulation of tumor cell proliferation and migration. Here we show, using MC38CEA murine colon carcinoma model, that ADAM17 also regulates tumor angiogenesis and cytokine profile. When ADAM17 was silenced in MC38CEA cells, in vivo tumor growth and in vitro cell motility were significantly diminished, but no effect was seen on in vitro cell proliferation. ADAM17-silencing was accompanied by decreased in vitro expression of vascular endothelial growth factor-A and matrix metalloprotease-9, which was consistent with the limited angiogenesis and slower growth seen in ADAM17-silenced tumors. Among the growth factors susceptible to shedding by ADAM17, neuregulin-1 was the only candidate to mediate the effects of ADAM17 on MC38CEA motility and tumor angiogenesis. Concentrations of TNF and IFNγ, cytokines that synergistically induced proapoptotic effects on MC38CEA cells, were significantly elevated in the lysates of ADAM17-silenced tumors compared to mock transfected controls, suggesting a possible role for ADAM17 in host immune suppression. These results introduce new, complex roles of ADAM17 in tumor progression, including its impact on the anti-tumor immune response. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
29. Mimitin -- a novel cytokine-regulated mitochondrial protein.
- Author
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Wegrzyn, Paulina, Yarwood, Stephen J., Fiegler, Nathalie, Bzowska, Monika, Koj, Aleksander, Mizgalska, Danuta, Malicki, Stanislaw, Pajak, Magdalena, Kasza, Aneta, Kachamakova-Trojanowska, Neli, Bereta, Joanna, Jura, Jacek, and Jura, Jolanta
- Subjects
CYTOKINES ,CELLS ,MITOCHONDRIA ,GENE expression ,PROTEINS - Abstract
Background: The product of a novel cytokine-responsive gene discovered by differential display analysis in our earlier studies on HepG2 cells was identified as mimitin -- a small mitochondrial protein. Since proinflammatory cytokines are known to affect components of the respiratory chain in mitochondria, and mimitin was reported as a possible chaperone for assembly of mitochondrial complex I, we looked for the effects of modulation of mimitin expression and for mimitin-binding partners. Results: By blocking mimitin expression in HepG2 cells by siRNA we found that mimitin has no direct influence on caspase 3/7 activities implicated in apoptosis. However, when apoptosis was induced by TNF and cycloheximide, and mimitin expression blocked, the activities of these caspases were significantly increased. This was accompanied by a slight decrease in proliferation of HepG2 cells. Our observations suggest that mimitin may be involved in the control of apoptosis indirectly, through another protein, or proteins. Using the yeast two-hybrid system and coimmunoprecipitation we found MAP1S among proteins interacting with mimitin. MAP1S is a recently identified member of the microtubule-associated protein family and has been shown to interact with NADH dehydrogenase I and cytochrome oxidase I. Moreover, it was implicated in the process of mitochondrial aggregation and nuclear genome destruction. The expression of mimitin is stimulated more than 1.6-fold by IL-1 and by IL-6, with the maximum level of mimitin observed after 18-24 h exposure to these cytokines. We also found that the cytokine-induced signal leading to stimulation of mimitin synthesis utilizes the MAP kinase pathway. Conclusion: Mimitin is a mitochondrial protein upregulated by proinflammatory cytokines at the transcriptional and protein levels, with MAP kinases involved in IL-1-dependent induction. Mimitin interacts with a microtubular protein (MAP1S), and some changes of mimitin gene expression modulate activity of apoptotic caspases 3/7, suggesting that this protein may indirectly participate in apoptosis. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
- View/download PDF
30. Control of Specific/Nonspecific Protein Adsorption: Functionalization of Polyelectrolyte Multilayer Films as a Potential Coating for Biosensors.
- Author
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Kruk, Tomasz, Bzowska, Monika, Hinz, Alicja, Szuwarzyński, Michał, and Szczepanowicz, Krzysztof
- Subjects
- *
MULTILAYERED thin films , *QUARTZ crystal microbalances , *ADSORPTION (Chemistry) , *STREPTAVIDIN , *DRUG delivery systems , *CARCINOEMBRYONIC antigen , *BIOSENSORS - Abstract
Control of nonspecific/specific protein adsorption is the main goal in the design of novel biomaterials, implants, drug delivery systems, and sensors. The specific functionalization of biomaterials can be achieved by proper surface modification. One of the important strategies is covering the materials with functional coatings. Therefore, our work aimed to functionalize multilayer coating to control nonspecific/specific protein adsorption. The polyelectrolyte coating was formed using a layer-by-layer technique (LbL) with biocompatible polyelectrolytes poly-L-lysine hydrobromide (PLL) and poly-L-glutamic acid (PGA). Nonspecific protein adsorption was minimized/eliminated by pegylation of multilayer films, which was achieved by adsorption of pegylated polycations (PLL-g-PEG). The influence of poly (ethylene glycol) chain length on eliminating nonspecific protein adsorption was confirmed. Moreover, to achieve specific protein adsorption, the multilayer film was also functionalized by immobilization of antibodies via a streptavidin bridge. The functional coatings were tested, and the adsorption of the following proteins confirmed the ability to control nonspecific/specific adsorption: human serum albumin (HSA), fibrinogen (FIB), fetal bovine serum (FBS), carcinoembryonic antigen human (CEA) monitored by quartz crystal microbalance with dissipation (QCM-D). AFM imaging of unmodified and modified multilayer surfaces was also performed. Functional multilayer films are believed to have the potential as a novel platform for biotechnological applications, such as biosensors and nanocarriers for drug delivery systems. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
31. Polyaminoacid Based Core@shell Nanocarriers of 5-Fluorouracil: Synthesis, Properties and Theranostics Application.
- Author
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Szczęch, Marta, Hinz, Alicja, Łopuszyńska, Natalia, Bzowska, Monika, Węglarz, Władysław P., and Szczepanowicz, Krzysztof
- Subjects
MAGNETIC resonance imaging ,NANOCARRIERS ,TARGETED drug delivery ,COMPANION diagnostics ,FLUOROURACIL - Abstract
Cancer is one of the most important health problems of our population, and one of the common anticancer treatments is chemotherapy. The disadvantages of chemotherapy are related to the drug's toxic effects, which act on cancer cells and the healthy part of the body. The solution of the problem is drug encapsulation and drug targeting. The present study aimed to develop a novel method of preparing multifunctional 5-Fluorouracil (5-FU) nanocarriers and their in vitro characterization. 5-FU polyaminoacid-based core@shell nanocarriers were formed by encapsulation drug-loaded nanocores with polyaminoacids multilayer shell via layer-by-layer method. The size of prepared nanocarriers ranged between 80–200 nm. Biocompatibility of our nanocarriers as well as activity of the encapsulated drug were confirmed by MTT tests. Moreover, the ability to the real-time observation of developed nanocarriers and drug accumulation inside the target was confirmed by fluorine magnetic resonance imaging (
19 F-MRI). [ABSTRACT FROM AUTHOR]- Published
- 2021
- Full Text
- View/download PDF
32. Structure, Biosynthesis, and Biological Activity of Succinylated Forms of Bacteriocin BacSp222.
- Author
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Śmiałek, Justyna, Nowakowski, Michał, Bzowska, Monika, Bocheńska, Oliwia, Wlizło, Agnieszka, Kozik, Andrzej, Dubin, Grzegorz, and Mak, Paweł
- Subjects
CIRCULAR dichroism ,EUKARYOTIC cells ,BIOSYNTHESIS ,KREBS cycle ,NUCLEAR magnetic resonance - Abstract
BacSp222 is a multifunctional peptide produced by Staphylococcus pseudintermedius 222. This 50-amino acid long peptide belongs to subclass IId of bacteriocins and forms a four-helix bundle molecule. In addition to bactericidal functions, BacSp222 possesses also features of a virulence factor, manifested in immunomodulatory and cytotoxic activities toward eukaryotic cells. In the present study, we demonstrate that BacSp222 is produced in several post-translationally modified forms, succinylated at the ε-amino group of lysine residues. Such modifications have not been previously described for any bacteriocins. NMR and circular dichroism spectroscopy studies have shown that the modifications do not alter the spatial structure of the peptide. At the same time, succinylation significantly diminishes its bactericidal and cytotoxic potential. We demonstrate that the modification of the bacteriocin is an effect of non-enzymatic reaction with a highly reactive intracellular metabolite, i.e., succinyl-coenzyme A. The production of succinylated forms of the bacteriocin depends on environmental factors and on the access of bacteria to nutrients. Our study indicates that the production of succinylated forms of bacteriocin occurs in response to the changing environment, protects producer cells against the autotoxicity of the excreted peptide, and limits the pathogenicity of the strain. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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33. Canine Respiratory Coronavirus, Bovine Coronavirus, and Human Coronavirus OC43: Receptors and Attachment Factors.
- Author
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Szczepanski, Artur, Owczarek, Katarzyna, Bzowska, Monika, Gula, Katarzyna, Drebot, Inga, Ochman, Marek, Maksym, Beata, Rajfur, Zenon, Mitchell, Judy A, and Pyrc, Krzysztof
- Subjects
CORONAVIRUSES ,SIALIC acids ,MOLECULES ,CELLS ,LEUCOCYTES - Abstract
Despite high similarity of canine respiratory coronavirus (CRCoV), bovine coronavirus, (BCoV) and human coronavirus OC43 (HCoV-OC43), these viruses differ in species specificity. For years it was believed that they share receptor specificity, utilizing sialic acids for cell surface attachment, internalization, and entry. Interestingly, careful literature analysis shows that viruses indeed bind to the cell surface via sialic acids, but there is no solid data that these moieties mediate virus entry. In our study, using a number of techniques, we showed that all three viruses are indeed able to bind to sialic acids to a different extent, but these molecules render the cells permissive only for the clinical strain of HCoV-OC43, while for others they serve only as attachment receptors. CRCoV and BCoV appear to employ human leukocyte antigen class I (HLA-1) as the entry receptor. Furthermore, we identified heparan sulfate as an alternative attachment factor, but this may be related to the cell culture adaptation, as in ex vivo conditions, it does not seem to play a significant role. Summarizing, we delineated early events during CRCoV, BCoV, and HCoV-OC43 entry and systematically studied the attachment and entry receptor utilized by these viruses. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
34. Improved Performance in Mammalian Cell Perfusion Cultures by Growth Inhibition.
- Author
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Wolf, Moritz K. F, Closet, Aurélie, Bzowska, Monika, Bielser, Jean‐Marc, Souquet, Jonathan, Broly, Hervé, and Morbidelli, Massimo
- Published
- 2019
- Full Text
- View/download PDF
35. Agglutinating mouse IgG3 compares favourably with IgMs in typing of the blood group B antigen: Functionality and stability studies.
- Author
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Klaus, Tomasz, Bzowska, Monika, Kulesza, Małgorzata, Kabat, Agnieszka Martyna, Jemioła-Rzemińska, Małgorzata, Czaplicki, Dominik, Makuch, Krzysztof, Jucha, Jarosław, Karabasz, Alicja, and Bereta, Joanna
- Published
- 2016
- Full Text
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36. A peptide factor secreted by Staphylococcus pseudintermedius exhibits properties of both bacteriocins and virulence factors.
- Author
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Wladyka, Benedykt, Piejko, Marcin, Bzowska, Monika, Pieta, Piotr, Krzysik, Monika, Mazurek, Łukasz, Guevara-Lora, Ibeth, Bukowski, Michał, Sabat, Artur J., Friedrich, Alexander W., Bonar, Emilia, Międzobrodzki, Jacek, Dubin, Adam, and Mak, Paweł
- Subjects
STAPHYLOCOCCUS ,STAPHYLOCOCCUS aureus ,BACTERIA ,GRAM-positive bacteria ,METHICILLIN-resistant staphylococcus aureus ,PATIENTS - Abstract
Staphylococcus pseudintermedius is a common commensal bacterium colonizing the skin and mucosal surfaces of household animals. However, it has recently emerged as a dangerous opportunistic pathogen, comparable to S. aureus for humans. The epidemiological situation is further complicated by the increasing number of methicillin-resistant S. pseudintermedius infections and evidence of gene transmission driving antibiotic resistance between staphylococci colonizing human and zoonotic hosts. In the present study, we describe a unique peptide, BacSp222, that possesses features characteristic of both bacteriocins and virulence factors. BacSp222 is secreted in high quantities by S. pseudintermedius strain 222 isolated from dog skin lesions. This linear, fifty-amino-acid highly cationic peptide is plasmid-encoded and does not exhibit significant sequence similarities to any other known peptides or proteins. BacSp222 kills gram-positive bacteria (at doses ranging from 0.1 to several micromol/l) but also demonstrates significant cytotoxic activities towards eukaryotic cells at slightly higher concentrations. Moreover, at nanomolar concentrations, the peptide also possesses modulatory properties, efficiently enhancing interferon gamma-induced nitric oxide release in murine macrophage-like cell lines. BacSp222 appears to be one of the first examples of multifunctional peptides that breaks the convention of splitting bacteriocins and virulence factors into two unrelated groups. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
37. Overcoming inefficient secretion of recombinant VEGF-C in baculovirus expression vector system by simple purification of the protein from cell lysate.
- Author
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Klaus, Tomasz, Kulesza, Małgorzata, Bzowska, Monika, Wyroba, Barbara, Kilarski, Witold W., and Bereta, Joanna
- Subjects
- *
VASCULAR endothelial growth factors , *PROTEIN expression , *BACULOVIRUSES , *RECOMBINANT proteins , *SECRETION - Abstract
The first reports about successfully expressed recombinant proteins with the use of a baculovirus vector were published over 30 years ago. Despite the long time of refining this expression system, early problems with the production of baculovirus-derived secretory proteins are still not satisfactorily solved. The high expression level driven by baculoviral promoters often does not result in the desired yield of secreted recombinant proteins, which frequently accumulate inside insect cells and are only partially processed. During our attempts to produce vascular endothelial growth factor C (VEGF-C) with the use of a baculovirus vector we also faced an inefficient secretion of the recombinant protein to culture medium. We were not able to improve the outcome and obtain an acceptable concentration of VEGF-C in the medium by changing the culture conditions or utilizing different signal peptides. However, as a significant amount of native VEGF-C was detected inside the baculovirus-infected cells, we developed a simple method to purify recombinant, glycosylated VEGF-C from a lysate of the cells. The presented results indicate that the lack of a secretory protein in the insect cell culture medium after baculovirus infection does not necessarily signify failure in the production of the protein. As demonstrated by us and contrary to generally accepted views, the lysate of baculovirus-infected cells may constitute a valuable source of the biologically active, secretory protein. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
38. A new expression vector facilitating production and functional analysis of scFv antibody fragments selected from Tomlinson I + J phagemid libraries.
- Author
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Ossysek, Karolina, Uchański, Tomasz, Kulesza, Małgorzata, Bzowska, Monika, Klaus, Tomasz, Woś, Klaudia, Madej, Mariusz, and Bereta, Joanna
- Subjects
- *
GENETIC vectors , *GENE libraries , *GENETIC code , *RECOMBINANT antibodies , *GENETIC testing , *BACTERIAL genes - Abstract
Tomlinson I + J are synthetic phagemid human scFv libraries widely employed to obtain specific antibody fragments via a phage display method. The pIT2/HB2151 expression system proposed by the designers of the libraries has certain drawbacks which result in the lack of expression or low expression levels of numerous soluble scFvs. At the stage of scFv screening, this may lead to losing some excellent antibodies, which can be avoided but requires laborious and expensive work. Here we present a new, pET-30-based vector, which is compatible with Tomlinson libraries, retains all virtues of pIT2 used as a plasmid and eliminates all its flaws. We demonstrate that pET-scFv-T is frequently superior to pIT2 in terms of efficient scFv expression. Moreover, an amber suppressor bacterial strain, RosettaBlue(DE3)pLysS, transformed with the new vector, pET-scFv-T, coding for a number of scFvs, produces substantial amounts of functional, easy to purify recombinant antibody fragments, regardless of whether their coding sequences contain amber codons. Thus, pET-scFv-T/RosettaBlue(DE3)pLysS expression system seems to be a perfect tool for screening for the finest soluble scFvs selected from Tomlinson I + J, as well as from many other phagemid libraries. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
39. Gadolinium labeled polyelectrolyte nanocarriers for theranostic application.
- Author
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Szczęch, Marta, Karabasz, Alicja, Łopuszyńska, Natalia, Bzowska, Monika, Węglarz, Władysław P., Warszyński, Piotr, and Szczepanowicz, Krzysztof
- Subjects
- *
NANOCARRIERS , *POLYELECTROLYTES , *GADOLINIUM , *NANOCAPSULES , *MAGNETIC resonance imaging , *ANTINEOPLASTIC agents , *PACLITAXEL , *CELL survival - Abstract
• The method of Gadolinium labeled polymeric nanocarriers was developed. • The empty nanocapsules did not affect the viability of the tested cells. • Encapsulated paclitaxel retained its strong cytotoxic/cytostatic activity. • Proposed nanocarriers can serve as an effective contrast agent that can be observed/monitored by MRI. Here, we designed a novel Gadolinium (Gd) labeled drug-loaded polyelectrolyte nanocarriers for theranostics. The nanocarriers were formed via layer-by-layer technique with biodegradable polyelectrolytes: PLL (Poly-L-lysine), PLL-Gd (Gadolinium-labeled Poly-L-lysine) and PGA (Poly-L-glutamic acid). Anticancer drug (Paclitaxel) was encapsulated in the formed nanocarriers. The average size of synthesized nanocarriers was around 150 nm. The empty gadolinium labeled nanocarriers did not show any deleterious effects on tested cells (CT26-CEA, B16F10, 4T1 and PBMC), whereas encapsulated paclitaxel retained its cytotoxic/cytostatic activity. Using T 2 and T 1 NMR relaxation measurements with 9.4 T preclinical MRI scanner, we demonstrated that gadolinium labeled nanocarriers can be detected due to a locally altered contrast in the MR image. Thus, they may become a promising platform for future theranostic applications. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
40. Addressing the Osteoporosis Problem-Multifunctional Injectable Hybrid Materials for Controlling Local Bone Tissue Remodeling.
- Author
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Gilarska A, Hinz A, Bzowska M, Dyduch G, Kamiński K, Nowakowska M, and Lewandowska-Łańcucka J
- Subjects
- Amines administration & dosage, Amines chemistry, Amines pharmacology, Animals, Biocompatible Materials administration & dosage, Biocompatible Materials chemistry, Bone Regeneration drug effects, Cell Line, Chitosan administration & dosage, Chitosan chemistry, Chitosan pharmacology, Collagen administration & dosage, Collagen chemistry, Collagen pharmacology, Drug Liberation, Humans, Hyaluronic Acid administration & dosage, Hyaluronic Acid chemistry, Hyaluronic Acid pharmacology, Injections, Subcutaneous, Materials Testing, Mice, Mice, Inbred C57BL, Osteoporosis pathology, Particle Size, Silicon Dioxide administration & dosage, Silicon Dioxide chemistry, Silicon Dioxide pharmacology, Biocompatible Materials pharmacology, Osteoporosis drug therapy, Tissue Engineering, Tissue Scaffolds chemistry
- Abstract
Novel multifunctional biomimetic injectable hybrid systems were synthesized. The physicochemical as well as biological in vitro and in vivo tests demonstrated that they are promising candidates for bone tissue regeneration. The hybrids are composed of a biopolymeric collagen/chitosan/hyaluronic acid matrix and amine group-functionalized silica particles decorated with apatite to which the alendronate molecules were coordinated. The components of these systems were integrated and stabilized by cross-linking with genipin, a compound of natural origin. They can be precisely injected into the diseased tissue in the form of a viscous sol or a partially cross-linked hydrogel, where they can serve as scaffolds for locally controlled bone tissue regeneration/remodeling by supporting the osteoblast formation/proliferation and maintaining the optimal osteoclast level. These materials lack systemic toxicity. They can be particularly useful for the repair of small osteoporotic bone defects.
- Published
- 2021
- Full Text
- View/download PDF
41. PorZ, an Essential Component of the Type IX Secretion System of Porphyromonas gingivalis , Delivers Anionic Lipopolysaccharide to the PorU Sortase for Transpeptidase Processing of T9SS Cargo Proteins.
- Author
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Madej M, Nowakowska Z, Ksiazek M, Lasica AM, Mizgalska D, Nowak M, Jacula A, Bzowska M, Scavenius C, Enghild JJ, Aduse-Opoku J, Curtis MA, Gomis-Rüth FX, and Potempa J
- Subjects
- Bacterial Secretion Systems genetics, Peptidyl Transferases genetics, Porphyromonas gingivalis enzymology, Porphyromonas gingivalis metabolism, Protein Binding, Protein Processing, Post-Translational, Protein Transport, Aminoacyltransferases metabolism, Bacterial Proteins genetics, Bacterial Proteins metabolism, Bacterial Secretion Systems metabolism, Cysteine Endopeptidases metabolism, Lipopolysaccharides metabolism, Peptidyl Transferases metabolism, Porphyromonas gingivalis genetics
- Abstract
Cargo proteins of the type IX secretion system (T9SS) in human pathogens from the Bacteroidetes phylum invariably possess a conserved C-terminal domain (CTD) that functions as a signal for outer membrane (OM) translocation. In Porphyromonas gingivalis , the CTD of cargos is cleaved off after translocation, and anionic lipopolysaccharide (A-LPS) is attached. This transpeptidase reaction anchors secreted proteins to the OM. PorZ, a cell surface-associated protein, is an essential component of the T9SS whose function was previously unknown. We recently solved the crystal structure of PorZ and found that it consists of two β-propeller moieties, followed by a CTD. In this study, we performed structure-based modeling, suggesting that PorZ is a carbohydrate-binding protein. Indeed, we found that recombinant PorZ specifically binds A-LPS in vitro Binding was blocked by monoclonal antibodies that specifically react with a phosphorylated branched mannan in the anionic polysaccharide (A-PS) component of A-LPS, but not with the core oligosaccharide or the lipid A endotoxin. Examination of A-LPS derived from a cohort of mutants producing various truncations of A-PS confirmed that the phosphorylated branched mannan is indeed the PorZ ligand. Moreover, purified recombinant PorZ interacted with the PorU sortase in an A-LPS-dependent manner. This interaction on the cell surface is crucial for the function of the "attachment complex" composed of PorU, PorZ, and the integral OM β-barrel proteins PorV and PorQ, which is involved in posttranslational modification and retention of T9SS cargos on the bacterial surface. IMPORTANCE Bacteria have evolved multiple systems to transport effector proteins to their surface or into the surrounding milieu. These proteins have a wide range of functions, including attachment, motility, nutrient acquisition, and toxicity in the host. Porphyromonas gingivalis , the human pathogen responsible for severe gum diseases (periodontitis), uses a recently characterized type IX secretion system (T9SS) to translocate and anchor secreted virulence effectors to the cell surface. Anchorage is facilitated by sortase, an enzyme that covalently attaches T9SS cargo proteins to a unique anionic lipopolysaccharide (A-LPS) moiety of P. gingivalis Here, we show that the T9SS component PorZ interacts with sortase and specifically binds A-LPS. Binding is mediated by a phosphorylated branched mannan repeat in A-LPS polysaccharide. A-LPS-bound PorZ interacts with sortase with significantly higher affinity, facilitating modification of cargo proteins by the cell surface attachment complex of the T9SS., (Copyright © 2021 Madej et al.)
- Published
- 2021
- Full Text
- View/download PDF
42. Mouse Antibody of IgM Class is Prone to Non-Enzymatic Cleavage between CH1 and CH2 Domains.
- Author
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Klaus T, Stalińska K, Czaplicki D, Mak P, Skupien-Rabian B, Kedracka-Krok S, Wiatrowska K, Bzowska M, Machula M, and Bereta J
- Subjects
- Amino Acid Sequence, Animals, HEK293 Cells, Hep G2 Cells, Humans, Hydrogen-Ion Concentration, Immunoglobulin Heavy Chains chemistry, Immunoglobulin Heavy Chains metabolism, Immunoglobulin M chemistry, Immunoglobulin M genetics, Mice, Mutagenesis, Site-Directed, Protein Domains, Immunoglobulin M metabolism
- Abstract
IgM is a multivalent antibody which evolved as a first line defense of adaptive immunity. It consists of heavy and light chains assembled into a complex oligomer. In mouse serum there are two forms of IgM, a full-length and a truncated one. The latter contains μ' chain, which lacks a variable region. Although μ' chain was discovered many years ago, its origin has not yet been elucidated. Our results indicate that μ' chain is generated from a full-length heavy chain by non-enzymatic cleavage of the protein backbone. The cleavage occurred specifically after Asn209 and is prevented by mutating this residue into any other amino acid. The process requires the presence of other proteins, preferentially with an acidic isoelectric point, and is facilitated by neutral or alkaline pH. This unique characteristic of the investigated phenomenon distinguishes it from other, already described, Asn-dependent protein reactions. A single IgM molecule is able to bind up to 12 epitopes via its antigen binding fragments (Fabs). The cleavage at Asn209 generates truncated IgM molecules and free Fabs, resulting in a reduced IgM valence and probably affecting IgM functionality in vivo.
- Published
- 2018
- Full Text
- View/download PDF
43. Antibody-based antiangiogenic and antilymphangiogenic therapies to prevent tumor growth and progression.
- Author
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Bzowska M, Mężyk-Kopeć R, Próchnicki T, Kulesza M, Klaus T, and Bereta J
- Subjects
- Disease Progression, Gene Expression Regulation, Humans, Lymphatic Metastasis, Neoplasms blood supply, Neoplasms genetics, Neoplasms pathology, Protein Isoforms antagonists & inhibitors, Protein Isoforms genetics, Receptors, Vascular Endothelial Growth Factor genetics, Signal Transduction, Vascular Endothelial Growth Factor A genetics, Antibodies, Monoclonal therapeutic use, Lymphangiogenesis drug effects, Neoplasms drug therapy, Neovascularization, Pathologic prevention & control, Receptors, Vascular Endothelial Growth Factor antagonists & inhibitors, Vascular Endothelial Growth Factor A antagonists & inhibitors
- Abstract
Blood and lymphatic vessel formation is an indispensable factor for cancer progression and metastasis. Therefore, various strategies designed to block angiogenesis and lymphangiogenesis are being investigated in the hope to arrest and reverse tumor development. Monoclonal antibodies, owing to their unequalled diversity and specificity, might be applied to selectively inhibit the pathways that cancer cells utilize to build up a network of blood vessels and lymphatics. Among the possible targets of antibody-based therapies are proangiogenic and prolymphangiogenic growth factors from the VEGF family and the receptors to which they bind (VEGFRs). Here, we present molecular mechanisms of angiogenesis and lymphangiogenesis exploited by tumors to progress and metastasise, with examples of antibody-based therapeutic agents directed at interfering with these processes. The expanding knowledge of vascular biology helps to explain some of the problems encountered in such therapies, that arise due to the redundancy in signaling networks controlling the formation of blood and lymphatic vessels, and lead to tumor drug resistance. Nonetheless, combined treatments and treatments focused on newly discovered proangiogenic and prolymphangiogenic factors give hope that more prominent therapeutic effects might be achieved in the future.
- Published
- 2013
44. Exogenous nitric oxide inhibits shedding of ADAM17 substrates.
- Author
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Bzowska M, Stalińska K, Mezyk-Kopeć R, Wawro K, Duda K, Das S, and Bereta J
- Subjects
- ADAM Proteins chemistry, ADAM Proteins deficiency, ADAM17 Protein, Animals, Antigens, Surface, Cell Line, Cell Line, Transformed, Endothelial Cells chemistry, Endothelial Cells drug effects, Endothelial Cells metabolism, Enzyme Precursors, Flow Cytometry, Kinetics, Macrophages chemistry, Macrophages drug effects, Macrophages metabolism, Metalloproteases metabolism, Mice, Nitric Oxide Donors metabolism, Protein Biosynthesis drug effects, RNA, Messenger drug effects, RNA, Messenger metabolism, Receptors, Tumor Necrosis Factor, Type I chemistry, Receptors, Tumor Necrosis Factor, Type I metabolism, Tumor Necrosis Factor-alpha chemistry, Tumor Necrosis Factor-alpha deficiency, Tumor Necrosis Factor-alpha metabolism, ADAM Proteins metabolism, Nitric Oxide metabolism, Nitric Oxide Donors pharmacology
- Abstract
Both ADAM17, the secretase responsible for the shedding of ectodomains of numerous membrane proteins including TNF and its receptors, as well as nitric oxide synthesized by inducible nitric oxide synthase play regulatory roles in inflammation and tumor progression. We analyzed the effect of endogenous and exogenous nitric oxide on the expression and activity of ADAM17 in murine endothelial cells and a monocyte/macrophage cell line. We found that endogenous nitric oxide influenced neither ADAM17 mRNA level nor the shedding of two ADAM17 substrates, TNF and TNFR1. Exogenous NO significantly diminished the release of TNF and TNFR1 without affecting the ADAM17 transcript level. Our data seem contrary to a previous report that showed the activation of ADAM17 by nitric oxide (Zhang et al., 2000, J Biol Chem 275: 15839-15844). We discuss potential mechanisms of NO-mediated inhibition of ectodomain shedding and possible reasons of discrepancy between our results and the previous report.
- Published
- 2009
45. Inactivation of membrane tumor necrosis factor alpha by gingipains from Porphyromonas gingivalis.
- Author
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Mezyk-Kopec R, Bzowska M, Potempa J, Bzowska M, Jura N, Sroka A, Black RA, and Bereta J
- Subjects
- Adhesins, Bacterial, Animals, Cell Line, Fibroblasts metabolism, Gingipain Cysteine Endopeptidases, HL-60 Cells metabolism, Humans, Mice, Porphyromonas gingivalis immunology, Cell Membrane metabolism, Cysteine Endopeptidases metabolism, Hemagglutinins metabolism, Porphyromonas gingivalis enzymology, Tumor Necrosis Factor-alpha antagonists & inhibitors
- Abstract
Gingipains are cysteine proteinases produced by Porphyromonas gingivalis, a major causative bacterium of adult periodontitis. They consist of arginine-specific (HRgpA and RgpB) and lysine-specific (Kgp) proteinases. Gingipains strongly affect the host defense system by degrading some cytokines, components of the complement system, and several immune cell receptors. In an in vitro model, gingipains were shown to degrade soluble tumor necrosis factor alpha (TNF-alpha). However, since membrane TNF-alpha shows strong biological activity, especially in local inflammatory lesions, it was worth investigating whether gingipains might also destroy membrane TNF-alpha and limit its biological activities. To avoid a possible influence of gingipains on ADAM17, the secretase of TNF-alpha, the majority of experiments were performed using ADAM17-/- fibroblasts stably transfected with cDNA of human pro-TNF-alpha (ADAM17-/- TNF+). Arginine-specific gingipains (Rgp's) strongly diminished the level of TNF-alpha on the cell surface as measured by flow cytometry, and this process was not accompanied by an increased concentration of soluble TNF-alpha in the culture medium. Degradation of membrane TNF-alpha by Rgp's correlated with a strong decrease in TNF-alpha-mediated biological activities of ADAM17-/- TNF+ cells. First, the activation state of transcription factor NF-kappaB was suppressed; second, the cells were no longer able to induce apoptosis in HL-60 cells. Kgp was also able to cleave membrane TNF-alpha, but its effect was much weaker than that of Rgp's. Gingipains also limited the binding of native TNF-alpha to the target cells. Thus, gingipains are able not only to cleave soluble TNF-alpha but also to destroy the membrane form of the cytokine, which may additionally dysregulate the cytokine network.
- Published
- 2005
- Full Text
- View/download PDF
46. Tumour necrosis factor-alpha stimulates expression of TNF-alpha converting enzyme in endothelial cells.
- Author
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Bzowska M, Jura N, Lassak A, Black RA, and Bereta J
- Subjects
- ADAM Proteins, ADAM17 Protein, Animals, Brain cytology, Brain enzymology, Cell Line, Transformed, Endothelium cytology, Endothelium drug effects, Endothelium enzymology, Enzyme-Linked Immunosorbent Assay, Mice, RNA, Messenger genetics, Recombinant Proteins pharmacology, Reverse Transcriptase Polymerase Chain Reaction, Transcription, Genetic, Brain drug effects, Gene Expression Regulation, Enzymologic drug effects, Metalloendopeptidases genetics, Tumor Necrosis Factor-alpha pharmacology
- Abstract
Tumor necrosis factor-alpha converting enzyme (ADAM17) is a major metalloproteinase involved in the shedding of several membrane-bound cytokines and cytokine receptors. Interplay of cytokines and their soluble receptors might be an important regulatory element in the network of interactions responsible for maintaining homeostasis in the immune system. ADAM17 thus has the potential to participate in a broad range of immune reactions. We studied the mechanisms of ADAM17 activation in endothelial cells and found that pro-inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta, interferon-gamma) and growth factors (epidermal growth factor, vascular endothelial growth factor) are able to upregulate transcription of ADAM17 and expression of ADAM17 protein. This process might constitute an important mechanism of regulation of ADAM17 activity. Stimulation of transcription, rather than increased ADAM17 mRNA stability, was responsible for increased levels of ADAM17 mRNA. Importantly, the increase in ADAM17 was accompanied by increased shedding of TNF-Receptor I (p55) in tumor necrosis factor-alpha-stimulated endothelial cells. Therefore, ADAM17-dependent depletion of membrane-bound tumor necrosis factor receptors from endothelial cells might constitute a mechanism of self-protection in states of prolonged immunostimulation.
- Published
- 2004
- Full Text
- View/download PDF
47. Structure and functions of tumor necrosis factor-alpha converting enzyme.
- Author
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Mezyk R, Bzowska M, and Bereta J
- Subjects
- ADAM Proteins, ADAM17 Protein, Animals, Enzyme Activation physiology, Metalloendopeptidases genetics, Metalloproteases genetics, Mice, Mice, Knockout, Protein Structure, Secondary genetics, Protein Structure, Secondary physiology, Substrate Specificity physiology, Metalloendopeptidases metabolism, Metalloproteases metabolism
- Abstract
Tumor necrosis factor-alpha converting enzyme (TACE) is the first described and best characterized secretase. In this review the structure and the possible roles for TACE are summarized. The substrate specificity and the regulation of TACE activity as well as redundancy and possible cooperations of distinct secretases are also discussed.
- Published
- 2003
- Full Text
- View/download PDF
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