RICARDO COSTA PETRONI
Projetos de Pesquisa
Unidades Organizacionais
LIM/51 - Laboratório de Emergências Clínicas, Hospital das Clínicas, Faculdade de Medicina
6 resultados
Resultados de Busca
Agora exibindo 1 - 6 de 6
- High-fat diet inhibits PGC-1 alpha suppressive effect on NF kappa B signaling in hepatocytes(2018) BARROSO, Wermerson Assuncao; VICTORINO, Vanessa Jacob; JEREMIAS, Isabela Casagrande; PETRONI, Ricardo Costa; ARIGA, Suely Kunimi Kubo; SALLES, Thiago A.; BARBEIRO, Denise Frediani; LIMA, Thais Martins de; SOUZA, Heraldo Possolo deThe peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) regulates the expression of genes implicated in fatty acid oxidation and oxidative phosphorylation. Its role in liver steatosis is well established, since mice with liver-specific deletion of PGC-1 alpha exhibit lipid accumulation and high-fat diet reduces hepatic PGC-1 alpha expression in mice. In this study, we investigated the role of PGC-1 alpha in the inflammatory changes observed in steatohepatitis induced by high-fat diet. C57black/6 mice were fed a high-fat diet containing 30% fat for 10 weeks. After euthanasia, liver morphology was examined by HE staining and inflammation was determined by IL-6, TNF-alpha, and IL-1 beta quantification. Liver gene expression of PGC-1 isoforms was evaluated by real-time PCR and p65 NF kappa B nuclear translocation by Western blotting. HepG2 cells were treated with linoleic acid overload for 72 h to create an in vitro model of steatohepatitis. RNA interference (RNAi) was used to evaluate the involvement of PGC-1 alpha on inflammatory mediators' production by hepatocytes. The high-fat diet led to a state of nonalcoholic steatohepatitis, associated with increased deposits of intra-abdominal fat, hyperglycemia and hyperlipidemia. Mice liver also exhibited increased proinflammatory cytokines' levels, decreased PGC-1 alpha expression, and marked increase in p65 NF kappa B nuclear translocation. Linoleic acid treated cells also presented increased expression of proinflammatory cytokines and decreased PGC-1 alpha expression. The knockdown of PGC-1 alpha content caused an increase in IL-6 expression and release via enhanced I kappa B alpha phosphorylation and subsequent increase of p65 NF kappa B nuclear translocation. High-fat diet induces liver inflammation by inhibiting PGC-1 alpha expression and its suppressive effect in NF kappa B pathway.
- 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.
- Hypertonic solution-induced preconditioning reduces inflammation and mortality rate(2019) PIMENTEL, Rosangela Nascimento; PETRONI, Ricardo Costa; BARBEIRO, Hermes Vieira; BARBEIRO, Denise Frediani; ANDRADE, Mariana Macedo; ARIGA, Suely Kumini; SORIANO, Francisco GarciaBackgroundDysregulated inflammatory response is common cause of organ damage in critical care patients. Preconditioning/tolerance is a strategy to prevent exacerbated inflammation. The aim of this study is to analyze hypertonic saline 7.5% as a potential inducer of preconditioning that protect from a lethal dose of LPS and modulates systemic inflammatory profile in mice.MethodsMale Balb/C mice received intravenous (i.v.) injections of Hypertonic solution (NaCl 7.5%) (0.8ml) for 3days, on day 8th was challenged with LPS 15mg/kg. Controls with Saline 0.9%, urea and sorbitol were performed. Microarray of mRNA expression was analyzed from HS versus saline from macrophages to identified the pathways activated by HS.ResultsHS preconditioning reduced mortality after LPS injection as well reduced the cytokines release in plasma of the animals challenged by LPS. In order to check how HS induces a preconditioning state we measured plasma cytokines after each HS infusion. Repeated HS injections induced a state of preconditioning that reprograms the inflammatory response, resulting in reduced inflammatory cytokine production. A microarray of mRNA demonstrated that Hypertonic solution increased the expression of several genes in special Mapkbp1 and Atf3.Conclusionhypertonic solution induces preconditioning/tolerance reducing mortality and inflammatory response after LPS challenge.
- Short-term Obesity Worsens Heart Inflammation and Disrupts Mitochondrial Biogenesis and Function in an Experimental Model of Endotoxemia(2022) PETRONI, Ricardo Costa; OLIVEIRA, Suelen Jeronymo Souza de; FUNGARO, Thais Pineda; ARIGA, Suely K. K.; BARBEIRO, Hermes Vieira; SORIANO, Francisco Garcia; LIMA, Thais Martins deCardiomyopathy is a well-known complication of sepsis that may deteriorate when accompanied by obesity. To test this hypothesis we fed C57black/6 male mice for 6 week with a high fat diet (60% energy) and submitted them to endotoxemic shock using E. coli LPS (10 mg/kg). Inflammatory markers (cytokines and adhesion molecules) were determined in plasma and heart tissue, as well as heart mitochondrial biogenesis and function. Obesity markedly shortened the survival rate of mouse after LPS injection and induced a persistent systemic inflammation since TNF alpha, IL-1 beta, IL-6 and resistin plasma levels were higher 24 h after LPS injection. Heart tissue inflammation was significantly higher in obese mice, as detected by elevated mRNA expression of pro-inflammatory cytokines (IL-1 beta, IL-6 and TNF alpha). Obese animals presented reduced maximum respiratory rate after LPS injection, however fatty acid oxidation increased in both groups. LPS decreased mitochondrial DNA content and mitochondria biogenesis factors, such as PGC1 alpha and PGC1 beta, in both groups, while NRF1 expression was significantly stimulated in obese mice hearts. Mitochondrial fusion/fission balance was only altered by obesity, with no influence of endotoxemia. Obesity accelerated endotoxemia death rate due to higher systemic inflammation and decreased heart mitochondrial respiratory capacity.
conferenceObject Hypertonic saline acts on septic lung remodeling through nitric oxide-induced FAK activation pathway(2013) PETRONI, Ricardo; BISELLI, Paolo; BARBEIRO, Hermes; KUBO, Suely; SORIANO, Francisco- Hypertonic Saline (NaCl 7.5 %) Reduces LPS-Induced Acute Lung Injury in Rats(2015) PETRONI, Ricardo Costa; BISELLI, Paolo Jose Cesare; LIMA, Thais Martins de; THEOBALDO, Mariana Cardillo; CALDINI, Elia Tamaso; PIMENTEL, Rosangela Nascimento; BARBEIRO, Hermes Vieira; KUBO, Suely Ariga; VELASCO, Irineu Tadeu; SORIANO, Francisco GarciaAcute respiratory distress syndrome (ARDS) is the most severe lung inflammatory manifestation and has no effective therapy nowadays. Sepsis is one of the main illnesses among ARDS causes. The use of fluid resuscitation is an important treatment for sepsis, but positive fluid balance may induce pulmonary injury. As an alternative, fluid resuscitation with hypertonic saline ((HS) NaCl 7.5 %) has been described as a promising therapeutical agent in sepsis-induced ARDS by the diminished amount of fluid necessary. Thus, we evaluated the effect of hypertonic saline in the treatment of LPS-induced ARDS. We found that hypertonic saline (NaCl 7.5 %) treatment in rat model of LPS-induced ARDS avoided pulmonary function worsening and inhibited type I collagen deposition. In addition, hypertonic saline prevented pulmonary injury by decreasing metalloproteinase 9 (MMP-9) activity in tissue. Focal adhesion kinase (FAK) activation was reduced in HS group as well as neutrophil infiltration, NOS2 expression and NO content. Our study shows that fluid resuscitation with hypertonic saline decreases the progression of LPS-induced ARDS due to inhibition of pulmonary remodeling that is observed when regular saline is used.