SERGIO PAULO BYDLOWSKI
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina - Docente
LIM/19 - Laboratório de Histocompatibilidade e Imunidade Celular, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/19 - Laboratório de Histocompatibilidade e Imunidade Celular, Hospital das Clínicas, Faculdade de Medicina - Líder
7 resultados
Resultados de Busca
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conferenceObject Increased Expression of Platelet Membrane Glycoprotein IIb/IIIa (GPIIb/IIIa) is Associated With Pulmonary Vasoreactivity After Pediatric Cardiac Surgery.(2018) MAEDA, Nair Y.; CLAVE, Mariana M.; CARVALHO, Eloisa S.; GALAS, Filomena R.; BYDLOWSKI, Sergio P.; LOPES, Antonio A.conferenceObject Effect of oxysterols in adipose tissue-derived mesenchymal stem cell(2018) LEVY, Debora; SILVA, Suelen; MELO, Thatiana; RUIZ, Jorge; ISAAC, Cesar; FIDELIS, Maira; RODRIGUES, Alessandro; BYDLOWSKI, Sergio- Snake Venom Extracellular vesicles (SVEVs) reveal wide molecular and functional proteome diversity(2018) CARREGARI, Victor Corassolla; ROSA-FERNANDES, Livia; BALDASSO, Paulo; BYDLOWSKI, Sergio Paulo; MARANGONI, Sergio; LARSEN, Martin R.; PALMISANO, GiuseppeProteins constitute almost 95% of snake venom's dry weight and are produced and released by venom glands in a solubilized form during a snake bite. These proteins are responsible for inducing several pharmacological effects aiming to immobilize and initiate the pre-digestion of the prey. This study shows that proteins can be secreted and confined in snake venom extracellular vesicles (SVEVs) presenting a size distribution between 50 nm and 500 nm. SVEVs isolated from lyophilized venoms collected from four different species of snakes (Agkistrodon contortrix contortrix, Crotalus atrox, Crotalus viridis and Crotalus cerberus oreganus) were analyzed by mass spectrometry-based proteomic, which allowed the identification of proteins belonging to eight main functional protein classes such as SVMPs, serine proteinases, PLA(2), LAAO, 5'nucleotidase, C-type lectin, CRISP and Disintegrin. Biochemical assays indicated that SVEVs are functionally active, showing high metalloproteinase and fibrinogenolytic activity besides being cytotoxic against HUVEC cells. Overall, this study comprehensively depicts the protein composition of SVEVs for the first time. In addition, the molecular function of some of the described proteins suggests a central role for SVEVs in the cytotoxicity of the snake venom and sheds new light in the envenomation process.
- Snake Venom Extracellular vesicles (SVEVs) reveal wide molecular and functional proteome diversity (vol 8, 15908,2018)(2018) CARREGARI, Victor Corassolla; ROSA-FERNANDES, Livia; BALDASSO, Paulo; BYDLOWSKI, Sergio Paulo; MARANGONI, Sergio; LARSEN, Martin R.; PALMISANO, Giuseppe
- Cell internalization of 7-ketocholesterol-containing nanoemulsion through LDL receptor reduces melanoma growth in vitro and in vivo: A preliminary report(2018) FAVERO, G. M.; PAZ, J. L.; OTAKE, A. H.; MARIA, D. A.; CALDINI, E. G.; MEDEIROS, R. S. S. de; DEUS, D. F.; CHAMMAS, R.; MARANHãO, R. C.; BYDLOWSKI, S. P.Oxysterols are cholesterol oxygenated derivatives which possess several biological actions. Among oxysterols, 7-ketocholesterol (7KC) is known to induce cell death. Here, we hypothesized that 7KC cytotoxicity could be applied in cancer therapeutics. 7KC was incorporated into a lipid core nanoemulsion. As a cellular model the murine melanoma cell line B16F10 was used. The nanoparticle (7KCLDE) uptake into tumor cells was displaced by increasing amounts of low-density-lipoproteins (LDL) suggesting a LDL-receptor-mediated cell internalization. 7KCLDE was mainly cytostatic, which led to an accumulation of polyploid cells. Nevertheless, a single dose of 7KCLDE killed roughly 10% of melanoma cells. In addition, it was observed dissipation of the transmembrane potential, evidenced with flow cytometry; presence of autophagic vacuoles, visualized and quantified with flow cytometry and acridine orange; and presence of myelin figures, observed with ultrastructural microscopy. 7KCLDE impaired cytokenesis was accompanied by changes in cellular morphology into a fibroblastoid shape which is supported by cytoskeletal rearrangements, as shown by the increased actin polymerization. 7KCLDE was injected into B16 melanoma tumor-bearing mice. 7KCLDE accumulated in the liver and tumor. In melanoma tumor 7KCLDE promoted a > 50% size reduction, enlarged the necrotic area, and reduced intratumoral vasculature. 7KCLDE increased the survival rates of animals, without hematologic or liver toxicity. Although more pre-clinical studies should be performed, our preliminary results suggested that 7KCLDE is a promising novel preparation for cancer chemotherapy. © Favero et al.
- Oxysterols selectively promote short-term apoptosis in tumor cell lines(2018) LEVY, Debora; MELO, Thatiana Correa de; OHIRA, Bianca Yumi; FIDELIS, Maira Luisa; RUIZ, Jorge L. M.; RODRIGUES, Alessandro; BYDLOWSKI, Sergio P.Oxysterols are 27-carbon oxidation products of cholesterol metabolism. Oxysterols possess several biological actions, including the promotion of cell death. Here, we examined the ability of several oxysterols to induce short-term death in cancerous (human breast cancer and mouse skin melanoma cells) and non-cancerous (human endothelial cells and lung fibroblasts) cell lines. We determined cell viability, Ki67 expression, cell cycle regulation, and apoptosis after 24-h incubations with oxysterols. We found that different oxysterols had different effects on the studied parameters. Moreover, the effects depended on cell type and oxysterol concentration. Three cytotoxic oxysterols (7-ketocholesterol, cholestane-3 beta-5 alpha-6 beta-triol, and 5 alpha-cholestane-3 beta,6 beta-diol) inhibited the S phase and stimulated the G0/G1 or G2/M phases. These oxysterols promoted apoptosis, determined with Annexin V and propidium iodide assays. These results showed that different oxysterols have cytotoxic effects depending on the cell line. The findings suggest a potential pharmacological utility of cytotoxic oxysterols.
- Integrated molecular, biochemical, and physiological assessment unravels key extraction method mediated influences on rat neonatal cardiomyocytes(2018) JENSEN, Leonardo; NERI, Elida; BASSANEZE, Vinicius; OLIVEIRA, Nathalia C. De Almeida; DARIOLLI, Rafael; TURACA, Lauro T.; LEVY, Debora; VERONEZ, Douglas; FERRAZ, Mariana S. A.; ALENCAR, Adriano M.; BYDLOWSKI, Sergio P.; CESTARI, Idagene A.; KRIEGER, Jose EduardoNeonatal cardiomyocytes are instrumental for disease modeling, but the effects of different cell extraction methods on basic cell biological processes remain poorly understood. We assessed the influence of two popular methods to extract rat neonatal cardiomyocytes, Pre-plating (PP), and Percoll (PC) on cell structure, metabolism, and function. Cardiomyocytes obtained from PP showed higher gene expression for troponins, titin, and potassium and sodium channels compared to PC. Also, PP cells displayed higher levels of troponin I protein. Cells obtained from PC displayed higher lactate dehydrogenase activity and lactate production than PP cells, indicating higher anaerobic metabolism after 8 days of culture. In contrast, reactive oxygen species levels were higher in PP cells as indicated by ethidium and hydroxyethidium production. Consistent with these data, protein nitration was higher in PP cells, as well as nitrite accumulation in cell medium. Moreover, PP cells showed higher global intracellular calcium under basal and 1mM isoprenaline conditions. In a calcium-transient assessment under electrical stimulation (0.5Hz), PP cells displayed higher calcium amplitude than cardiomyocytes obtained from PC and using a traction force microscope technique we observed that PP cardiomyocytes showed the highest relaxation. Collectively, we demonstrated that extraction methods influence parameters related to cell structure, metabolism, and function. Overall, PP derived cells are more active and mature than PC cells, displaying higher contractile function and generating more reactive oxygen species. On the other hand, PC derived cells display higher anaerobic metabolism, despite comparable high yields from both protocols.