MARISA PASSARELLI
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina
LIM/10 - Laboratório de Lípides, Hospital das Clínicas, Faculdade de Medicina
LIM/10 - Laboratório de Lípides, Hospital das Clínicas, Faculdade de Medicina
11 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 11
- Exercise Training Favorably Modulates Gene and Protein Expression That Regulate Arterial Cholesterol Content in CETP Transgenic Mice(2018) PINTO, Paula R.; SILVA, Karolline S. da; IBORRA, Rodrigo T.; OKUDA, Ligia S.; GOMES-KJERULF, Diego; FERREIRA, Guilherme S.; MACHADO-LIMA, Adriana; ROCCO, Debora D. F. M.; NAKANDAKARE, Edna R.; MACHADO, Ubiratan F.; CORREA-GIANNELLA, Maria L.; CATANOZI, Sergio; PASSARELLI, MarisaAerobic exercise training (AET) improves the reverse cholesterol transport (RCT) in cholesteryl ester transfer protein-transgenic (CETP-tg) mice. We aimed at investigating the role of AET in the expression of genes and proteins involved in lipid flux in the aorta and macrophages of CETP-tg mice. Three-month-old male mice were randomly divided into trained (T; treadmill 15 m/min; 30 min/day) and sedentary (S) groups. After 6 weeks, peritoneal macrophages and the aortic arch were obtained immediately (0 h) or 48 h after the last exercise session. mRNA was determined by RT-qPCR, protein levels by immunoblot and C-14-cholesterol efflux determined in macrophages. AET did not change body weight, plasma cholesterol, triglycerides, glucose and CETP activity. In macrophages, at time 0 h, a higher expression of genes that encode PPAR gamma, ABCA-1 and a lower expression of MCP-1 and IL-10, was observed in T as compared to S. After 48 h, lower expressions of MCP-1 and PPAR gamma genes were observed in T mice. Increase in ABCA-1, SR-BI and IL-6 and decrease of LOX-1, MCP-1, TNF and IL-10 gene expression was observed in the aorta of T compared to S mice (0 h) and LOX-1 and MCP-1 remained diminished after 48 h. The protein level of MCP-1 and SR-BI in the aortic arch was unchanged in T animals after 48 h as compared to S, but LOX-1 was reduced confirming data of gene expression. The apo A-I and the HDL2 mediated-cholesterol efflux (8 and 24 h) were not different between T and S animals. In the presence of CETP, AET positively influences gene expression in the arterial wall and macrophages of CETP-tg mice contributing to the RCT and prevention of atherosclerosis. These changes were perceptible immediately after the exercise session and were influenced by the presence of CETP although independent of changes in its activity. Reductions in gene and protein expression of LOX-1 were parallel and reflect the ability of exercise training in reducing the uptake of modified LDL by the arterial wall macrophages.
conferenceObject Increased serum expression of miR-518d-3p and miR-618 in individuals with type 1 diabetes with microvascular chronic complications(2018) SANTOS-BEZERRA, D. P.; SANTOS, A. S.; GUIMARAES, G. C.; ADMONI, S. N.; PEREZ, R. V.; PELAES, T. S.; MACHADO, C. G.; PASSARELLI, M.; MACHADO, U. F.; QUEIROZ, M. S.; SILVA, M. E. R.; CORREA-GIANNELLA, M. L. C.conferenceObject Diminished macrophage cholesterol efflux mediated by HDL and coronary artery disease in young male anabolic androgenic steroid users(2018) SOUZA, F. R.; SANTOS, M. R.; PORELLO, R. A.; FONSECA, G. W. P.; SAYEGH, A. L. C.; LIMA, T. P.; FERREIRA, F. D.; OLIVEIRA, T. F.; YONAMINE, M.; TAKAYAMA, L.; PEREIRA, R. M. R.; NEGRAO, C. E.; PASSARELLI, M.; ROCHITTE, C. E.; ALVES, M. J. N. N.conferenceObject ADVANCED GLYCATED APOAIV IS LESS EFFICIENT IN REDUCING INFLAMMATION IN MACROPHAGES AND UNABLE TO PREVENT THE REDUCTION IN ABCA1 AND ABCG1 MRNA INDUCED BY LPS(2018) OKUDA, L. Shimabukuro; IBORRA, R. Tallada; PINTO, P. Ramos; PATEL, M.; MACHADO, U. Fabres; RYE, K. A.; PASSARELLI, M.- IN TYPE 1 DIABETES MELLITUS IMPAIRED VASCULAR FUNCTION RELATES TO THE EXPRESSION OF MYD88 IN LYMPHOMONONUCLEAR CELLS BUT NOT TO DIETARY ADVANCED GLYCATION END-PRODUCTS(2018) TOYOSHIMA, M. T. K.; SANTOS-BEZERRA, D. P.; MACHADO-LIMA, A.; GOES, M. F. S.; CARAMELLI, B.; CORREA-GIANNELLA, M. L. C.; PASSARELLI, M.
- Palmitate-induced Slc2a4/GLUT4 downregulation in L6 muscle cells: evidence of inflammatory and endoplasmic reticulum stress involvement(2018) EBERSBACH-SILVA, Patricia; POLETTO, Ana Claudia; DAVID-SILVA, Aline; SERAPHIM, Patricia Monteiro; ANHE, Gabriel Forato; PASSARELLI, Marisa; FURUYA, Daniela Tomie; MACHADO, Ubiratan FabresBackground: Obesity is strongly associated to insulin resistance, inflammation, and elevated plasma free fatty acids, but the mechanisms behind this association are not fully comprehended. Evidences suggest that endoplasmic reticulum (ER) stress may play a role in this complex pathophysiology. The aim of the present study was to investigate the involvement of inflammation and ER stress in the modulation of glucose transporter GLUT4, encoded by Slc2a4 gene, in L6 skeletal muscle cells. Methods: L6 cells were acutely (2 h) and chronically (6 and 12 h) exposed to palmitate, and the expression of several proteins involved in insulin resistance, ER stress and inflammation were analyzed. Results: Chronic and acute palmitate exposure significantly reduced GLUT4 protein (similar to 39%, P < 0.01) and its mRNA (18%, P < 0.01) expression. Only acute palmitate treatment increased GRP78 (28%, P < 0.05), PERK (98%, P < 0.01), eIF-2A (35%, P < 0.01), IRE1a (60%, P < 0.05) and TRAF2 (23%, P < 0.05) protein content, and PERK phosphorylation (106%, P < 0.001), but did not elicit eIF-2A, IKK phosphorylation or increased XBP1 nuclear content. Additionally, acute and chronic palmitate increased NFKB p65 nuclear content (similar to 30%, P < 0.05) and NFKB binding activity to Slc2a4 gene promoter (similar to 45%, P < 0.05). Conclusion: Different pathways are activated in acute and chronic palmitate induced-repression of Slc2a4/GLUT4 expression. This regulation involves activation of initial component of ER stress, such as the formation of a IRE1a-TRAF2-IKK complex, and converges to NFKB-induced repression of Slc2a4/GLUT4. These results link ER stress, inflammation and insulin resistance in L6 cells.
conferenceObject IMPROVEMENT OF GLYCEMIC CONTROL RESTORES ABCA-1 IN MACROPHAGES INCUBATED WITH ALBUMIN ISOLATED FROM DIABETIC SUBJECTS(2018) IBORRA, R. Tallada; MACHADO-LIMA, A.; OKUDA, L. S.; MINANNI, C.; MELLO, M.; NAKANDAKARE, E. R.; MACHADO, U. F.; CORREA-GIANELLA, M. L. C.; PASSARELLI, M.- Dietary advanced glycated end-products and medicines influence the expression of SIRT1 and DDOST in peripheral mononuclear cells from long-term type 1 diabetes patients(2018) SANTOS-BEZERRA, Daniele P.; MACHADO-LIMA, Adriana; MONTEIRO, Maria Beatriz; ADMONI, Sharon N.; PEREZ, Ricardo V.; MACHADO, Cleide G.; SHIMIZU, Maria Heloiza; CAVALEIRO, Ana M.; THIEME, Karina; QUEIROZ, Marcia S.; MACHADO, Ubiratan F.; GIANNELLA-NETO, Daniel; PASSARELLI, Marisa; CORREA-GIANNELLA, Maria LuciaQuantitative polymerase chain reaction was employed to quantify expression of two genes coding for advanced glycation end-product receptors [RAGE (AGER) and AGER1 (DDOST)] and of the gene coding the deacetylase SIRT1 (SIRT1) in peripheral blood mononuclear cells from type 1 diabetes patients without [Group A, n = 35; 28.5 (24-39) years old; median (interquartile interval)] or with at least one microvascular complication [Group B, n = 117; 34.5 (30-42) years old]; 31 healthy controls were also included. In a subgroup of 48 patients, daily advanced glycation end-products intake before blood collection was assessed. Lower expression of DDOST was found in patients than in controls after adjustment for sex, age, use of statins, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Higher expressions of AGER, DDOST and SIRT1 were observed in Group A. Stratifying by complications, AGER and DDOST expressions were higher in those without retinopathy and without diabetic kidney disease, respectively, compared to patients with these complications. Patients using statins or angiotensin receptor blockers presented higher expression of DDOST. Expression of SIRT1 was higher in patients consuming >= 12,872 KU daily of advanced glycation end-products. Although AGER, DDOST and SIRT1 are differently expressed in peripheral blood mononuclear cells from type 1 diabetes patients with and without microvascular complications, they are also influenced by dietary advanced glycation end-products and by statins and angiotensin receptor blockers.
- Advanced glycation end products-induced insulin resistance involves repression of skeletal muscle GLUT4 expression(2018) PINTO-JUNIOR, Danilo C.; SILVA, Karolline S.; MICHALANI, Maria L.; YONAMINE, Caio Y.; ESTEVES, Joao V.; FABRE, Nelly T.; THIEME, Karina; CATANOZI, Sergio; OKAMOTO, Maristela M.; SERAPHIM, Patricia M.; CORREA-GIANNELLA, Maria L.; PASSARELLI, Marisa; MACHADO, Ubiratan F.Little is known about advanced glycation end products (AGEs) participation in glucose homeostasis, a process in which skeletal muscle glucose transporter GLUT4 (Scl2 alpha 4 gene) plays a key role. This study investigated (1) the in vivo and in vitro effects of AGEs on Slc2 alpha 4/GLUT4 expression in skeletal muscle of healthy rats, and (2) the potential involvement of endoplasmic reticulum and inflammatory stress in the observed regulations. For in vivo analysis, rats were treated with advanced glycated rat albumin (AGE-albumin) for 12 weeks; for in vitro analysis, soleus muscles from normal rats were incubated with bovine AGE-albumin for 2.5 to 7.5 hours. In vivo, AGE-albumin induced whole-body insulin resistance; decreased (similar to 30%) Slc2 alpha 4 mRNA and GLUT4 protein content; and increased (similar to 30%) the nuclear content of nuclear factor NF-kappa-B p50 subunit (NFKB1), and cellular content of 78 kDa glucose-regulated protein (GRP78). In vitro, incubation with AGE-albumin decreased (similar to 50%) the Slc2 alpha 4/GLUT4 content; and increased cellular content of GRP78/94, phosphorylated-IKK-alpha/beta, nuclear content of NFKB1 and RELA, and the nuclear protein binding into Slc2 alpha 4 promoter NFKB-binding site. The data reveal that AGEs impair glucose homeostasis in non-diabetic states of increased AGEs concentration; an effect that involves activation of endoplasmic reticulum-and inflammatory-stress and repression of Slc2 alpha 4/GLUT4 expression.
- AGE-albumin enhances ABCA1 degradation by ubiquitin-proteasome and lysosomal pathways in macrophages(2018) IBORRA, Rodrigo Tallada; MACHADO-LIMA, Adriana; OKUDA, Ligia Shimabukuro; PINTO, Paula Ramos; NAKANDAKARE, Edna Regina; MACHADO, Ubiratan Fabres; CORREA-GIANNELLA, Maria Lucia; PICKFORD, Russell; WOODS, Tom; BRIMBLE, Margaret A.; RYE, Kerry-Anne; LU, Rui; YOKOYAMA, Shinji; PASSARELLI, MarisaBackground and aims: Advanced glycation end products (AGEs) induce cellular oxidative/endoplasmic reticulum stress and inflammation. We investigated its underlying mechanisms for atherogenesis focusing on regulation of ABCA1 protein decay in macrophages. Methods: The ABCA1 decay rate was evaluated in macrophages after treatment with LXR agonist and by incubation with control (C) or AGE-albumin concomitant or not with cycloheximide, MG-132, ammonium chloride and calpain inhibitors were utilized to inhibit, respectively, proteasome, lysosome and ABCA1 proteolysis at cell surface. ABCA1 was determined by immunoblot and the protein decay rate calculated along time by the slope of the linear regression. Ubiquitination level was determined in ABCA1 immunoprecipitated from whole cell lysate or bulk cell membrane. AGE effect was also analyzed in THP-1 cells transfected with siRNA-RAGE. Carboxymethyllysine (CML) and pyrraline (PYR) were determined by LC/MS. One-way ANOVA and Student t test were utilized to compare results. Results: CML and PYR-albumin were higher in AGE-albumin as compared to C. AGE-albumin reduced ABCA1 in J774 and THP-1 macrophages (20-30%) and induced a higher ABCA1 ubiquitination and a faster protein decay rate that was dependent on the presence of AGE during the kinetics of measurement in the presence of cycloheximide. Proteasomal inhibition restored and lysosomal inhibition partially recovered ABCA1 in cells treated with AGE-albumin. Calpain inhibition was not able to rescue ABCA1. RAGE knockdown prevented the reduction in ABCA1 elicited by AGE. Conclusions: AGE-albumin.diminishes ABCA1 by accelerating its degradation through the proteasomal and lysosomal systems. This may increase lipid accumulation in macrophages by diminishing cholesterol efflux via RAGE signaling contributing to atherosclerosis in diabetes mellitus.