KAROLLINE SANTANA DA SILVA

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LIM/10 - Laboratório de Lípides, Hospital das Clínicas, Faculdade de Medicina

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  • article 7 Citação(ões) na Scopus
    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, Marisa
    Aerobic 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.
  • article 57 Citação(ões) na Scopus
    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.