RICARDO COSTA PETRONI
Projetos de Pesquisa
Unidades Organizacionais
LIM/51 - Laboratório de Emergências Clínicas, Hospital das Clínicas, Faculdade de Medicina
2 resultados
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- PGC-1 beta regulates HER2-overexpressing breast cancer cells proliferation by metabolic and redox pathways(2016) VICTORINO, Vanessa Jacob; BARROSO, W. A.; ASSUNCAO, A. K. M.; CURY, V.; JEREMIAS, I. C.; PETRONI, R.; CHAUSSE, B.; ARIGA, S. K.; HERRERA, A. C. S. A.; PANIS, C.; LIMA, T. M.; SOUZA, H. P.Breast cancer is a prevalent neoplastic disease among women worldwide which treatments still present several side effects and resistance. Considering that cancer cells present derangements in their energetic homeostasis, and that peroxisome proliferator-activated receptor- gamma coactivator 1 (PGC-1) is crucial for cellular metabolism and redox signaling, the main objective of this study was to investigate whether there is a relationship between PGC-1 expression, the proliferation of breast cancer cells and the mechanisms involved. We initially assessed PGC-1 beta expression in complementary DNA (cDNA) from breast tumor of patients bearing luminal A, luminal B, and HER2-overexpressed and triple negative tumors. Our data showed that PGC-1 beta expression is increased in patients bearing HER2-overexpressing tumors as compared to others subtypes. Using quantitative PCR and immunoblotting, we showed that breast cancer cells with HER2-amplification (SKBR-3) have greater expression of PGC-1 beta as compared to a non-tumorous breast cell (MCF-10A) and higher proliferation rate. PGC-1 beta expression was knocked down with short interfering RNA in HER2-overexpressing cells, and cells decreased proliferation. In these PGC-1 beta-inhibited cells, we found increased citrate synthase activity and no marked changes in mitochondrial respiration. Glycolytic pathway was decreased, characterized by lower intracellular lactate levels. In addition, after PGC-1 beta knockdown, SKBR-3 cells showed increased reactive oxygen species production, no changes in antioxidant activity, and decreased expression of ERR alpha, a modulator of metabolism. In conclusion, we show an association of HER2overexpression and PGC-1 beta. PGC-1 beta knockdown impairs HER2-overexpressing cells proliferation acting on ERR alpha signaling, metabolism, and redox balance.
- Creatine supplementation attenuates pulmonary and systemic effects of lung ischemia and reperfusion injury(2016) ALMEIDA, Francine Maria; OLIVEIRA-JUNIOR, Manoel Carneiro; SOUZA, Renato Aparecido; PETRONI, Ricardo Costa; SOTO, Sonia Fatima; SORIANO, Francisco Garcia; CARVALHO, Paulo Tarso Camillo de; ALBERTINI, Regiane; DAMACENO-RODRIGUES, Nilsa Regina; LOPES, Fernanda Degobbi Tenorio Quirino Santos; CASTRO-FARIA-NETO, Hugo Caire; MARTINS, Milton Arruda; DOLHNIKOFF, Marisa; PAZETTI, Rogerio; VIEIRA, Rodolfo PaulaBACKGROUND: Creatine (Cr) is a dietary supplement that presents beneficial effects in experimental models of heart and brain ischemia and reperfusion (I/R) injury. It can improve adenosine 5'-triphosphate generation and reduce cell damage This study evaluated the effects of Cr supplementation in a model of lung PR. METHODS: Forty male Wistar rats were divided into 4 groups: sham operated, Cr+sham, I/R, and Cr+I/R. We investigated the effects of 5 days of Cr supplementation (0.5 g/kg/day by gavage) before left pulmonary artery ischemia (90 minutes) and reperfusion (120 minutes) on pulmonary and systemic response. RESULTS: Cr inhibited the I/R-induced increase in exhaled nitric oxide (p < 0.05), total cells (p < 0.01), and neutrophils (p < 0.001) in bronchoalveolar lavage fluid and in the systemic circulation (p < 0.001). The levels of interleulcin-1 beta (p < 0.05), tissue damping, and tissue elastance (p < 0.05) were also minimized Cr also inhibited pulmonary edema formation (total proteins in bronchoalveolar lavage fluid, p < 0.001; histologic edema index, p < 0.001) and neutrophils accumulation in lung tissue (p < 0.001). As possible mechanisms underlying Cr effects, we observed a reduced expression of caspase 3 (p < 0.05), reduced expression of Toll-like receptor (TLR) 4, and increased expression of TLR7 in lung tissue (p < 0.001). CONCLUSIONS: Cr supplementation presents pulmonary and systemic protective effects in acute lung injury induced by I/R in rats. These beneficial effects seem to be related to the anti-inflammatory and antioxidant properties of Cr and modulation of TLRs.