Disintegrins and disintegrins-like proteins are able to inhibit platelet aggregation and integrin-mediated cell adhesion. The aim of this study was to produce one disintegrin-like cloned from Bothrops leucurus venom gland and to characterize it regarding biological activity. The recombinant protein was purified by one step procedure involving anion-exchange chromatography (DEAE-cellulose) and presented a molecular mass of 10.4 kDa. The purified protein was able to inhibit platelet aggregation induced by collagen (IC₅₀ = 0.65 μM) and to inhibit growth of Ehrlich tumor implanted in mice by more than 50% after 7 days administration of 10 μg/day. No effects were observed upon adenosine 5'-diphosphate (ADP)-and arachidonic acid (AA)-induced platelet aggregation. The recombinant protein was recognized by an antibody specific for jararhagin one metalloproteinase isolated from Bothrops jararaca venom, and therefore it was named leucurogin. Anti-angiogenesis effect of leucurogin was evaluated by the sponge implant model. After 7 days administration leucurogin inhibited, in a dose dependent way, the vascularization process in the sponge. Leucurogin represents a new biotechnological tool to understand biological processes where disintegrins-like are involved and may help to characterize integrins that can be involved in development and progression of malignant cells.
To assess the importance of carbohydrate moieties to the antiangiogenic activity of plasminogen fragments, we cloned the fragment corresponding to amino acids Val 79 to Thr 346 (Kint3-4) that presents the three glycosylation sites. The activity of glycosylated and unglycosylated Kint3-4 was tested in murine sponge implant model. We observed a significant decrease in the neovascularization on the sponge after treatment with Kint3-4 by histological examination and determination of the hemoglobin levels. The effects were more intense with the glycosylated than the unglycosylated protein. Technecium-labeled red blood cells confirmed the inhibition of cell infiltration in the implanted sponge. Studies using melanoma B16F1 implanted in a mouse demonstrated that treatment with glycosylated Kint3-4 (0.15 nmol ⁄ 48 h) during 14 days suppresses tumor growth by 80%. The vascular endothelial growth factor mRNA levels on the tumor were reduced after treatment. Kint3-4 is a potent plasminogen fragment that has been found to inhibit tumor growth. (Cancer Sci 2010; 101: 453-459) T he vasculature is an important organ. Angiogenesis, the formation of new blood vessels from pre-existing capillaries, is a fundamental and complex process involved in reproduction, cellular development, and pathological events, such as inflammation, diabetic retinopathy, endometriosis, adiposity, and cancer.(1,2) During tumor growth and chronic inflammation, neovascularization is required for the provision of nutrients and oxygen and to mobilize host cells, such as leukocytes. (3,4) The new vascular network demands an extensive interplay between cells, soluble factors, and extracellular components, and is tightly regulated by the expression of angiogenic and angiostatic factors.(5,6) A wide range of molecules mediates angiogenesis by acting directly or indirectly on endothelial cells via accessory cells, such as polymorphonuclear leukocytes.(7-9) Among these molecules are fragments of the plasmatic glycoprotein plasminogen, which have different angiostatic activity. Plasminogen presents five segments that, because of their specific structure, were designated as kringles (K1-K5). The antiproliferative activity of plasminogen is shared by K1, K2, K3, and K4 being the most potent angiostatin (K1-4 corresponding to amino acids Cys 84 -Cys 435 ), followed by K2-3. (10,11) The sequence numbering of plasminogen starts with Glu 1 of the mature protein or Glu 20 for human plasminogen when including signal peptide. K2 and K3 individually or in combination exhibit weak activity when compared with K2-3, and a combination of K1-3 and K4 resulted in the same activity level of K1-4.(11) It was also observed that the most potent inhibitor of endothelial cell angiogenesis of is K1-3 (amino acids Cys 84 -Cys 333 of plasminogen). (12) These results show that proteolytic processing with the exposure of antiangiogenic sites, kringle conformation, interkringle interaction, and carbohydrate moieties can alter efficiency and function. Despite the anti-angiogenic activity...
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RESUMOA educação ambiental pode ser considerada por toda ação educativa que contribui para a formação de cidadãos conscientes da preservação do meio ambiente, aptos também a tomar decisões coletivas necessárias para o desenvolvimento de uma sociedade sustentável. Uma das formas de ter a ação de extensão é por meio de projetos com caráter educativo. O presente artigo considera que atividades lúdicas, em especial o teatro, possa contribuir para uma educação ambiental mais significativa, promovendo a prática e a reflexão crítica, com o intuito de desenvolver cidadãos capazes de conceber uma responsabilidade ambiental. Esta proposta une o ensino de ciências com a realização de experimentos químicos à expressão teatral na busca da valorização dos conceitos aprendidos. O teatro foi apresentado ao ensino fundamental II na rede pública e a validação da pesquisa foi realizada com aplicação de questionários pré e pós apresentação, abordando temas relacionados com a responsabilidade socioambiental. Os resultados coletados corroboram com outros autores, demonstrando que a prática do teatro é uma ferramenta educacional, favorecendo assimilação de conceitos e neste caso, auxiliando na conscientização ambiental. Palavras-chave: Educação ambiental. Teatro. Ensino de Ciências. ABSTRACTEnvironmental education can be understood with all educational action that contributes to the formation of citizens aware of the preservation of the environment and able to make collective decisions on environmental issues necessary for the development of a sustainable society. One of the ways of having the extension action is through projects with an educational character. The present article considers that ludic activities, especially theater, can contribute to a more meaningful environmental education, promoting practical and critical reflection, with the intention of developing citizens capable of conceiving an environmental responsibility. his proposal unites the teaching of sciences with the accomplishment of chemical experiments to the theatrical expression in the search of the valorization of the concepts learned. The theater was presented to elementary school II in the public network and the validation of the research was carried out with the application of pre and post presentation questionnaires, addressing themes related to social and environmental responsibility. The results collected corroborate with other authors, demonstrating that the practice of theater is an educational tool, favoring assimilation of concepts and in this case, it assists in environmental awareness.
As proteínas são macromoléculas formadas por polímeros de aminoácidos constituídas por carbono, hidrogênio e oxigênio e ligados entre si através de ligações peptídicas, podendo ser de origem animal ou vegetal. Sua estrutura determina diversos fatores, tornando-as responsáveis por funções vitais para os seres vivos, pois fornecem material tanto para a construção como para a manutenção dos nossos órgãos e tecidos. Sendo assim, é indispensável compreender seus aspectos estruturais e os mesmos atrelados, principalmente, a sua função. De acordo com o Currículo Do Estado De São Paulo Ciências da Natureza e Suas Tecnologias, o estudo das proteínas é abordado no segundo ano do ensino médio. Além do mais, também é estudo em níveis superiores de formação. Por serem estruturas complexas, ao abordar tal assunto, métodos didáticos podem colaborar no entendimento de forma prática e ilustrativa os fenômenos que as envolvem. Com base nesses dados, este trabalho traz propostas de representação de proteínas para o nível médio e superior com materiais acessíveis e de baixo custo envolvendo representação de sua estrutura e função com experimentos práticos. Buscando com que o aluno relacione a prática com o teórico e amplifique sua capacidade de compreensão do conteúdo de forma lúdica, tornando o processo de construção de conhecimento científico mais atraente, tendo em vista que a química é uma matéria de difícil aprendizagem devido a sua complexidade e a abstração de determinados conceitos.
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