Expressão gênica das interleucinas IL-4, IL-10, IL-12 e de interferon gama no baço de gatos infectados por Leishmania infantum chagasi

Pós-graduação em Ciência Animal - FMVA

Changes in gene expression in PBMCs profiles of PPAR alpha target genes in obese and non-obese individuals during fasting

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Radiação gama na conservação de caqui 'Giombo', destanizado e frigoarmazenado

O caqui apresenta uma safra curta, sendo necessário estender seu período de comercialização utilizando técnicas adequadas de armazenamento. O objetivo deste trabalho foi avaliar o uso da radiação gama na qualidade pós-colheita de caquis 'Giombo' destanizados. Frutos colhidos meio-maduros e com aproximadamente 50 % da coloração verde, foram destanizados, acondicionados em bandejas de poliestireno expandido (EPS), revestidas por filme plástico de polietileno de baixa densidade (PEBD) e submetidos à radiação gama (60Co). Os frutos foram armazenados durante 35 dias, sob refrigeração (0±0,5 ºC e 85 ± 0,5% UR). Os tratamentos realizados foram: T1 - 0,0 kGy; T2 - 0,3 kGy; T3 - 0,6 kGy; T4 - 0,9 kGy; T5 - 1,2 kGy. As análises realizadas a cada 7 dias foram: perda de massa, atividade respiratória, teores de sólidos solúveis (SS), ácido ascórbico, acidez titulável (AT) e relação SS/AT. Os frutos submetidos à dose de 0,6 kGy apresentaram o menor percentual de perda de massa e produção de CO2 ao longo do período experimental. Os teores de SS e AT permaneceram estáveis e sem diferenças devido às doses de irradiação aplicadas. Os tratamentos com 0,3 KGy e 0,6 KGy foram os mais eficazes na manutenção da firmeza nos caquis. Nos teores de ácido ascórbico, observou-se redução ao longo do período experimental, sendo os menores valores apresentados para a maior dose de irradiação (1,2 KGy).

Bounds on effective interactions from the reaction e+e--->gama gama at LEP

We establish bounds on the mass scale of effective interactions between fermions and photons using the OPAL data for the reaction e+e-→γγ at √s=91.22 GeV.

Gama-Lactones from Iryanthera species

The structure of juruenolide, a constituent of Iryanthera juruensis and I. ulei is revised to (2S, 3R, 4S)-3-hydroxy-4-methyl-2-(19′-piperonyl-1′-n-nonadecyl)-butanolide. The compound is epimeric at C-3 of the γ-lactone unit with grandinolide [(2S, 3S, 4S)-3-hydroxy-4-methyl-2- (19′-phenyl-1′-n-nonadecyl)-butanolide] from I. grandis. An extract of I. juruensis contained additionally juruenolide-B [(4S)-4-methyl-2-(19′-piperonyl-1′-n-nonadec-7′-enyl)-but-2-enolide]. Analogous products with heptadecyl and pentadecyl side chains co-occur with the respective nonadecyl derivatives. © 1983.

Produção de bebida mista de extrato hidrossolúvel de soja e suco de uva submetida a diferentes doses de radiação gama

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Avaliação enzimática na pós-colheita do maná cubiu tratados com radiação gama

The objective of this study was to evaluate the effects of gamma radiation on fruit quality and conservation of mana cubiu through its enzymatic characteristics, with 20 days of storage and 5 taken every 4 days. The fruits selected were subjected to different doses of gamma radiation Co60 (0.0; 0.2; 0.4; 0.6 and 0.8 kGy) packaged in trays of expanded polyethylene then covered with stretchable PVC film associated with refrigerated stored at 10 ± 3°C e 85 ± 5% de UR and evaluated in six periods (0, 4, 8, 12, 16 e 20 days). The variables evaluated were: enzymatic activity of pectin (PME), polygalacturonase (PG), polyphenoloxidase (PPO) and peroxidase (POD). For PG there was no interaction between dose and storage on the day 16 the highest value to 640.10 UE min-1 g-1 and 0.8 kGy dose showed the lowest with 376.37 10 UE min-1 g-1. PME now get in 16 days and 0.8 kGy dose the highest values of the experiment, to 290.74 UE min-1 g-1. In POF, the day 16 presented the value of 0.26 min-1 g-1 of dry mass-1. In 20 days the fruits of all treatments provided the highest values of POD during the experiment. The results showed that different doses of gamma radiation does not interfere with the activity of the enzymes determined in this experiment.

Expressão gênica de interferon-gama, fator de necrose tumoral alfa e interleucinas 2 e 5 no baço de gatos naturalmente infectados por Leishmania spp: Karina Yukie Hirata. -

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Tauroursodeoxycholic Acid Affects PPAR gamma and TLR4 in Steatotic Liver Transplantation

Numerous steatotic livers are discarded for transplantation because of their poor tolerance to ischemia-reperfusion (I/R). We examined whether tauroursodeoxycholic acid (TUDCA), a known inhibitor of endoplasmic reticulum (ER) stress, protects steatotic and nonsteatotic liver grafts preserved during 6 h in University of Wisconsin (UW) solution and transplanted. The protective mechanisms of TUDCA were also examined. Neither unfolded protein response (UPR) induction nor ER stress was evidenced in steatotic and nonsteatotic liver grafts after 6 h in UW preservation solution. TUDCA only protected steatotic livers grafts and did so through a mechanism independent of ER stress. It reduced proliferator-activated receptor-gamma(PPAR gamma) and damage. When PPAR gamma was activated, TUDCA did not reduce damage. TUDCA, which inhibited PPAR gamma, and the PPAR gamma antagonist treatment up-regulated toll-like receptor 4 (TLR4), specifically the TIR domain-containing adaptor inducing IFN beta (TRIF) pathway. TLR4 agonist treatment reduced damage in steatotic liver grafts. When TLR4 action was inhibited, PPAR gamma antagonists did not protect steatotic liver grafts. In conclusion, TUDCA reduced PPAR gamma and this in turn up-regulated the TLR4 pathway, thus protecting steatotic liver grafts. TLR4 activating-based strategies could reduce the inherent risk of steatotic liver failure after transplantation.

Major involvement of mTOR in the PPAR gamma-induced stimulation of adipose tissue lipid uptake and fat accretion

Evidence points to a role of the mammalian target of rapamycin (mTOR) signaling pathway as a regulator of adiposity, yet its involvement as a mediator of the positive actions of peroxisome proliferator-activated receptor (PPAR)gamma agonism on lipemia, fat accretion, lipid uptake, and its major determinant lipoprotein lipase (LPL) remains to be elucidated. Herein we evaluated the plasma lipid profile, triacylglycerol (TAG) secretion rates, and adipose tissue LPL-dependent lipid uptake, LPL expression/activity, and expression profile of other lipid metabolism genes in rats treated with the PPAR gamma agonist rosiglitazone (15 mg/kg/day) in combination or not with the mTOR inhibitor rapamycin (2 mg/kg/day) for 15 days. Rosiglitazone stimulated adipose tissue mTOR complex 1 and AMPK and induced TAG-derived lipid uptake (136%), LPL mRNA/activity (2- to 6-fold), and fat accretion in subcutaneous (but not visceral) white adipose tissue (WAT; 50%) and in brown adipose tissue (BAT; 266%). Chronic mTOR inhibition attenuated the upregulation of lipid uptake, LPL expression/activity, and fat accretion induced by PPAR gamma activation in both subcutaneous WAT and BAT, which resulted in hyperlipidemia. In contrast, rapamycin did not affect most of the other WAT lipogenic genes upregulated by rosiglitazone. Together these findings demonstrate that mTOR is a major regulator of adipose tissue LPL-mediated lipid uptake and a critical mediator of the hypolipidemic and lipogenic actions of PPAR gamma activation.-Blanchard, P-G., W. T. Festuccia, V. P. Houde, P. St-Pierre, S. Brule, V. Turcotte, M. Cote, K. Bellmann, A. Marette, and Y. Deshaies. Major involvement of mTOR in the PPAR gamma-induced stimulation of adipose tissue lipid uptake and fat accretion. J. Lipid Res. 2012. 53: 1117-1125.

Advanced QSAR Studies on PPAR delta Ligands Related to Metabolic Diseases

PPAR delta is a nuclear receptor that, when activated, regulates the metabolism of carbohydrates and lipids and is related to metabolic syndrome and type 2 diabetes. To understand the main interactions between ligands and PPAR delta, we have constructed 2D and 3D QSAR models and compared them with HOMO, LUMO and electrostatic potential maps of the compounds studied, as well as docking results. All QSAR models showed good statistical parameters and prediction outcomes. The QSAR models were used to predict the biological activity of an external test set, and the predicted values are in good agreement with the experimental results. Furthermore, we employed all maps to evaluate the possible interactions between the ligands and PPAR delta. These predictive QSAR models, along with the HOMO, LUMO and MEP maps, can provide insights into the structural and chemical properties that are needed in the design of new PPAR delta ligands that have improved biological activity and can be employed to treat metabolic diseases.

PPAR gamma activation attenuates cold-induced upregulation of thyroid status and brown adipose tissue PGC-1 alpha and D2

Festuccia WT, Blanchard PG, Oliveira TB, Magdalon J, Paschoal VA, Richard D, Deshaies Y. PPAR gamma activation attenuates cold-induced upregulation of thyroid status and brown adipose tissue PGC-1 alpha and D2. Am J Physiol Regul Integr Comp Physiol 303: R1277-R1285, 2012. First published October 24, 2012; doi:10.1152/ajpregu.00299.2012.-Here, we investigated whether pharmacological PPAR gamma activation modulates key early events in brown adipose tissue (BAT) recruitment induced by acute cold exposure with the aim of unraveling the interrelationships between sympathetic and PPAR gamma signaling. Sprague-Dawley rats treated or not with the PPAR gamma ligand rosiglitazone (15 mg.kg(-1).day(-1), 7 days) were kept at 23 degrees C or exposed to cold (5 degrees C) for 24 h and evaluated for BAT gene expression, sympathetic activity, thyroid status, and adrenergic signaling. Rosiglitazone did not affect the reduction in body weight gain and the increase in feed efficiency, VO2, and BAT sympathetic activity induced by 24-h cold exposure. Rosiglitazone strongly attenuated the increase in serum total and free T4 and T3 levels and BAT iodothyronine deiodinase type 2 (D2) and PGC-1 alpha mRNA levels and potentiated the reduction in BAT thyroid hormone receptor (THR) beta mRNA levels induced by cold. Administration of T3 to rosiglitazone-treated rats exacerbated the cold-induced increase in energy expenditure but did not restore a proper activation of D2 and PGC-1 alpha, nor further increased uncoupling protein 1 expression. Regarding adrenergic signaling, rosiglitazone did not affect the changes in BAT cAMP content and PKA activity induced by cold. Rosiglitazone alone or in combination with cold increased CREB binding to DNA, but it markedly reduced the expression of one of its major coactivators, CREB binding protein. In conclusion, pharmacological PPAR gamma activation impairs short-term cold elicitation of BAT adrenergic and thyroid signaling, which may result in abnormal tissue recruitment and thermogenic activity.

Combined effect of AMPK/PPAR agonists and exercise training in mdx mice functional performance

The present investigation was undertaken to test whether exercise training (ET) associated with AMPK/PPAR agonists (EM) would improve skeletal muscle function in mdx mice. These drugs have the potential to improve oxidative metabolism. This is of particular interest because oxidative muscle fibers are less affected in the course of the disease than glycolitic counterparts. Therefore, a cohort of 34 male congenic C57Bl/10J mdx mice included in this study was randomly assigned into four groups: vehicle solution (V), EM [AICAR (AMPK agonist, 50 mg/Kg-1.day-1, ip) and GW 1516 (PPAR delta agonist, 2.5 mg/Kg-1.day-1, gavage)], ET (voluntary running on activity wheel) and EM+ET. Functional performance (grip meter and rotarod), aerobic capacity (running test), muscle histopathology, serum creatine kinase (CK), levels of ubiquitined proteins, oxidative metabolism protein expression (AMPK, PPAR, myoglobin and SCD) and intracellular calcium handling (DHPR, SERCA and NCX) protein expression were analyzed. Treatments started when the animals were two months old and were maintained for one month. A significant functional improvement (p<0.05) was observed in animals submitted to the combination of ET and EM. CK levels were decreased and the expression of proteins related to oxidative metabolism was increased in this group. There were no differences among the groups in the intracellular calcium handling protein expression. To our knowledge, this is the first study that tested the association of ET with EM in an experimental model of muscular dystrophy. Our results suggest that the association of ET and EM should be further tested as a potential therapeutic approach in muscular dystrophies.

Medium Chain Fatty Acids Are Selective Peroxisome Proliferator Activated Receptor (PPAR) gamma Activators and Pan-PPAR Partial Agonists

Thiazolidinediones (TZDs) act through peroxisome proliferator activated receptor (PPAR) gamma to increase insulin sensitivity in type 2 diabetes (T2DM), but deleterious effects of these ligands mean that selective modulators with improved clinical profiles are needed. We obtained a crystal structure of PPAR gamma ligand binding domain (LBD) and found that the ligand binding pocket (LBP) is occupied by bacterial medium chain fatty acids (MCFAs). We verified that MCFAs (C8-C10) bind the PPAR gamma LBD in vitro and showed that they are low-potency partial agonists that display assay-specific actions relative to TZDs; they act as very weak partial agonists in transfections with PPAR gamma LBD, stronger partial agonists with full length PPAR gamma and exhibit full blockade of PPAR gamma phosphorylation by cyclin-dependent kinase 5 (cdk5), linked to reversal of adipose tissue insulin resistance. MCFAs that bind PPAR gamma also antagonize TZD-dependent adipogenesis in vitro. X-ray structure B-factor analysis and molecular dynamics (MD) simulations suggest that MCFAs weakly stabilize C-terminal activation helix (H) 12 relative to TZDs and this effect is highly dependent on chain length. By contrast, MCFAs preferentially stabilize the H2-H3/beta-sheet region and the helix (H) 11-H12 loop relative to TZDs and we propose that MCFA assay-specific actions are linked to their unique binding mode and suggest that it may be possible to identify selective PPAR gamma modulators with useful clinical profiles among natural products.