Browsing by Author "Silva, Danielle Gomes Passos"

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    Discovery and characterization of Alamandine : a novel component of the Renin-Angiotensin system.
    (2013) Lautner, Roberto Queiroga; Villela, Daniel Campos; Silva, Rodrigo Araújo Fraga da; Silva, Neiva Caldeira; Braga, Thiago Verano; Fraga, Fabiana Costa; Jankowski, Joachim; Jankowski, Vera; Sousa, Frederico Barros de; Alzamora, Andréia Carvalho; Soares, Everton Rocha; Barbosa, Claudiane Maria; Kjeldsen, Frank; Oliveira, Aline Cristina; Braga, Janaina Félix; Savergnini, Silvia Silveira Quintão; Etelvino, Gisele Maia; Peluso, Antonio Augusto Bastos; Silva, Danielle Gomes Passos; Ferreira, Anderson José; Alves, Fabiana; Martins, Almir de Sousa; Raizada, Mohan K.; Paula, Renata Dutra de; Santos, Daisy Motta; Klempin, Friederike; Pimenta, Adriano Monteiro de Castro; Alenina, Natalia; Sinisterra Millán, Ruben Dario; Bader, Michael; Santos, Maria José Campagnole dos; Santos, Robson Augusto Souza dos
    The renin–angiotensin system (RAS) is a key regulator of the cardiovascular system, electrolyte, and water balance. Here, we report identification and characterization of alamandine, a new heptapeptide generated by catalytic action of angiotensin-converting enzyme-2 angiotensin A or directly from angiotensin-(1–7). To characterize a novel component of the RAS, alamandine. Using mass spectrometry we observed that alamandine circulates in human blood and can be formed from angiotensin-(1–7) in the heart. Alamandine produces several physiological actions that resemble those produced by angiotensin-(1–7), including vasodilation, antifibrosis, antihypertensive, and central effects. Interestingly, our data reveal that its actions are independent of the known vasodilator receptors of the RAS, Mas, and angiotensin II type 2 receptor. Rather, we demonstrate that alamandine acts through the Mas-related G-protein–coupled receptor, member D. Binding of alamandine to Mas-related G-protein–coupled receptor, member D is blocked by D-Pro7-angiotensin-(1–7), the Mas-related G-protein–coupled receptor, member D ligand β-alanine and PD123319, but not by the Mas antagonist A-779. In addition, oral administration of an inclusion compound of alamandine/β-hydroxypropyl cyclodextrin produced a long-term antihypertensive effect in spontaneously hypertensive rats and antifibrotic effects in isoproterenol-treated rats. Alamandine had no noticeable proliferative or antiproliferative effect in human tumoral cell lines. The identification of these 2 novel components of the RAS, alamandine and its receptor, provides new insights for the understanding of the physiological and pathophysiological role of the RAS and may help to develop new therapeutic strategies for treating human cardiovascular diseases and other related disorders.
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    Effect of ionizing radiation exposure on Trypanosoma cruzi ubiquitin-proteasome system.
    (2017) Cerqueira, Paula Gonçalves; Silva, Danielle Gomes Passos; Rocha, João Pedro Vieira da; Mendes, Isabela Cecilia; Oliveira, Karla Andrade de; Oliveira, Camila Franco Batista de; Vilela, Liza Figueiredo Felicori; Nagem, Ronaldo Alves Pinto; Cardoso, Josiane; Nardelli, Sheila Cristina; Krieger, Marco Aurélio; Franco, Glória Regina; Macedo, Andréa Mara; Pena, Sérgio Danilo Junho; Schenkman, Sérgio; Gomes, Dawidson Assis; Cota, Renata Guerra de Sá; Machado, Carlos Renato
    tIn recent years, proteasome involvement in the damage response induced by ionizing radiation (IR)became evident. However, whether proteasome plays a direct or indirect role in IR-induced damageresponse still unclear. Trypanosoma cruzi is a human parasite capable of remarkable high tolerance toIR, suggesting a highly efficient damage response system. Here, we investigate the role of T. cruzi pro-teasome in the damage response induced by IR. We exposed epimastigotes to high doses of gamma rayand we analyzed the expression and subcellular localization of several components of the ubiquitin-proteasome system. We show that proteasome inhibition increases IR-induced cell growth arrest andproteasome-mediated proteolysis is altered after parasite exposure. We observed nuclear accumulationof 19S and 20S proteasome subunits in response to IR treatments. Intriguingly, the dynamic of 19S par-ticle nuclear accumulation was more similar to the dynamic observed for Rad51 nuclear translocationthan the observed for 20S. In the other hand, 20S increase and nuclear translocation could be relatedwith an increase of its regulator PA26 and high levels of proteasome-mediated proteolysis in vitro. Theintersection between the opposed peaks of 19S and 20S protein levels was marked by nuclear accumu-lation of both 20S and 19S together with Ubiquitin, suggesting a role of ubiquitin-proteasome system inthe nuclear protein turnover at the time. Our results revealed the importance of proteasome-mediatedproteolysis in T. cruzi IR-induced damage response suggesting that proteasome is also involved in T. cruziIR tolerance. Moreover, our data support the possible direct/signaling role of 19S in DNA damage repair.Based on these results, we speculate that spatial and temporal differences between the 19S particle and20S proteasome controls proteasome multiple roles in IR damage response.