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
46 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 46
- 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.
- Postmortem Brains from Subjects with Diabetes Mellitus Display Reduced GLUT4 Expression and Soma Area in Hippocampal Neurons: Potential Involvement of Inflammation(2023) YONAMINE, Caio Yogi; PASSARELLI, Marisa; SUEMOTO, Claudia Kimie; PASQUALUCCI, Carlos Augusto; JACOB-FILHO, Wilson; ALVES, Venancio Avancini Ferreira; MARIE, Suely Kazue Nagahashi; CORREA-GIANNELLA, Maria Lucia; BRITTO, Luiz Roberto; MACHADO, Ubiratan FabresDiabetes mellitus (DM) is an important risk factor for dementia, which is a common neurodegenerative disorder. DM is known to activate inflammation, oxidative stress, and advanced glycation end products (AGEs) generation, all capable of inducing neuronal dysfunctions, thus participating in the neurodegeneration progress. In that process, disturbed neuronal glucose supply plays a key role, which in hippocampal neurons is controlled by the insulin-sensitive glucose transporter type 4 (GLUT4). We investigated the expression of GLUT4, nuclear factor NF-kappa B subunit p65 [NFKB (p65)], carboxymethyllysine and synapsin1 (immunohistochemistry), and soma area in human postmortem hippocampal samples from control, obese, and obese+DM subjects (41 subjects). Moreover, in human SH-SY5Y neurons, tumor necrosis factor (TNF) and glycated albumin (GA) effects were investigated in GLUT4, synapsin-1 (SYN1), tyrosine hydroxylase (TH), synaptophysin (SYP) proteins, and respective genes; NFKB binding activity in the SLC2A4 promoter; effects of increased histone acetylation grade by histone deacetylase 3 (HDAC3) inhibition. Hippocampal neurons (CA4 area) of obese+DM subjects displayed reduced GLUT4 expression and neuronal soma area, associated with increased expression of NFKB (p65). Challenges with TNF and GA decreased the SLC2A4/GLUT4 expression in SH-SY5Y neurons. TNF decreased SYN1, TH, and SYP mRNAs and respective proteins, and increased NFKB binding activity in the SLC2A4 promoter. Inhibition of HDAC3 increased the SLC2A4 expression and the total neuronal content of CRE-binding proteins (CREB/ICER), and also counterbalanced the repressor effect of TNF upon these parameters. This study revealed reduced postmortem human hippocampal GLUT4 content and neuronal soma area accompanied by increased proinflammatory activity in the brains of DM subjects. In isolated human neurons, inflammatory activation by TNF reduced not only the SLC2A4/GLUT4 expression but also the expression of some genes related to neuronal function (SYN1, TH, SYP). These effects may be related to epigenetic regulations (H3Kac and H4Kac status) since they can be counterbalanced by inhibiting HDAC3. These results uncover the improvement in GLUT4 expression and/or the inhibition of HDAC3 as promising therapeutic targets to fight DM-related neurodegeneration.
conferenceObject CHRONIC ADMINISTRATION OF ALBUMIN MODIFIED BY ADVANCED GLYCATION (AGE) INDUCES EXPRESSION OF PRO-FIBROTIC, PRO-APOPTOTIC AND RENIN-ANGIOTENSIN SYSTEM GENES ON RENAL TISSUE(2016) THIEME, Karina; FABRE, Nelly Takashima; SILVA, Karolline Santana da; CATANOZI, Sergio; MONTEIRO, Maria Beatriz; MACHADO, Ubiratan Fabres; PASSARELLI, Marisa; CORREA-GIANNELLA, Maria Lucia CardilloconferenceObject LIPOPROTEINS AND LIPID METABOLISM: HDL. AEROBIC EXERCISE TRAINING DOES NOT SYSTEMATICALLY AFFECT MACROPHAGE GENE EXPRESSION INVOLVED IN REVERSE CHOLESTEROL TRANSPORT AND CHOLESTEROL EFFLUX IN CETP TRANSGENIC MICE(2016) PINTO, P. R.; SILVA, K. S.; GOMES, D. J.; MACHADO-LIMA, A.; IBORRA, R. T.; FERREIRA, G. S.; QUINTAO, E. C. R.; NAKANDAKARE, E. R.; MACHADO, U. F.; CORREA-GIANNELLA, M. L. C.; CATANOZI, S.; PASSARELLI, M.conferenceObject Associations of genetic variants in thioredoxin (TXN) and mitochondrial thioredoxin reductase (TXNRD2) genes with kidney disease in type 1 diabetes(2013) PATENTE, T. A.; MONTEIRO, M. B.; QUEIROZ, M.; NERY, M.; AZEVEDO, M. J.; CANANI, L. H.; PAVIN, E. J.; PARISI, M. C.; MACHADO, U. F.; PASSARELLI, M.; GIANNELLA-NETO, D.; CORREA-GIANNELLA, M. L. C.- Urinary Sediment Transcriptomic and Longitudinal Data to Investigate Renal Function Decline in Type 1 Diabetes(2020) MONTEIRO, Maria Beatriz; PELAES, Tatiana S.; SANTOS-BEZERRA, Daniele P.; THIEME, Karina; LERARIO, Antonio M.; OBA-SHINJO, Sueli M.; MACHADO, Ubiratan F.; PASSARELLI, Marisa; MARIE, Suely K. N.; CORREA-GIANNELLA, Maria LuciaIntroduction: Using a discovery/validation approach we investigated associations between a panel of genes selected from a transcriptomic study and the estimated glomerular filtration rate (eGFR) decline across time in a cohort of type 1 diabetes (T1D) patients. Experimental: Urinary sediment transcriptomic was performed to select highly modulated genes in T1D patients with rapid eGFR decline (decliners) vs. patients with stable eGFR (non-decliners). The selected genes were validated in samples from a T1D cohort (n = 54, mean diabetes duration of 21 years, 61% women) followed longitudinally for a median of 12 years in a Diabetes Outpatient Clinic. Results: In the discovery phase, the transcriptomic study revealed 158 genes significantly different between decliners and non-decliners. Ten genes increasingly up or down-regulated according to renal function worsening were selected for validation by qRT-PCR; the genes CYP4F22, and PMP22 were confirmed as differentially expressed comparing decliners vs. non-decliners after adjustment for potential confounders. CYP4F22, LYPD3, PMP22, MAP1LC3C, HS3ST2, GPNMB, CDH6, and PKD2L1 significantly modified the slope of eGFR in T1D patients across time. Conclusions: Eight genes identified as differentially expressed in the urinary sediment of T1D patients presenting different eGFR decline rates significantly increased the accuracy of predicted renal function across time in the studied cohort. These genes may be a promising way of unveiling novel mechanisms associated with diabetic kidney disease progression.
- Leukotriene Pathway Activation Associates with Poor Glycemic Control and with Cardiovascular Autonomic Neuropathy in Type 1 Diabetes(2020) SANTOS-BEZERRA, Daniele P.; FILGUEIRAS, Luciano R.; MONTEIRO, Maria Beatriz; ADMONI, Sharon N.; V, Ricardo Perez; CAVALEIRO, Ana M.; MACHADO, Cleide G.; MACHADO, Ubiratan F.; PASSARELLI, Marisa; JANCAR, Sonia; CORREA-GIANNELLA, Maria LuciaBackground and Aims. Since hyperglycemia promotes inflammation by different pathways and inflammation participates in the development of chronic diabetes complications, we investigated the association between the leukotriene (LT) pathway and microvascular diabetes complications. Methods and Results. Quantitative polymerase chain reaction was employed to quantify the expression of ALOX5 (encodes 5-lipoxygenase), LTB4R (encodes one of the LTB4 receptors), and MYD88 in peripheral blood mononuclear cells from 164 type 1 diabetes (T1D) individuals presenting or not diabetes kidney disease, retinopathy, peripheral neuropathy, and cardiovascular autonomic neuropathy (CAN); 26 nondiabetic subjects were included as controls. LTB4 plasmatic concentrations were also evaluated. The expression of LTB4R was significantly higher in T1D individuals than in controls. T1D individuals with microvascular complications presented lower MYD88 mRNA expression when compared to those without microvascular complications. Higher LTB4 concentrations were found in individuals with CAN versus without CAN. The observation of two distinct subgroups of T1D individuals in the correlation analyses motivated us to evaluate the characteristics of each one of these groups separately. The group presenting higher expression of ALOX5 and of LTB4R also presented higher values of HbA(1)C, of fructosamine, and of plasmatic LTB4. Conclusion. In the diabetes setting, the LT pathway is not only activated by hyperglycemia but is also modulated by the status of the autonomic nervous system.
- Beta-2-microglobulin (B2M) expression in the urinary sediment correlates with clinical markers of kidney disease in patients with type 1 diabetes(2016) MONTEIRO, Maria Beatriz; THIEME, Karina; SANTOS-BEZERRA, Daniele Pereira; QUEIROZ, Marcia Silva; WORONIK, Viktoria; PASSARELLI, Marisa; MACHADO, Ubiratan Fabres; GIANNELLA-NETO, Daniel; OLIVEIRA-SOUZA, Maria; CORREA-GIANNELLA, Maria LuciaPurpose. After observing variation in the expression of the housekeeping gene B2M in cells of the urinary sediment during a study of candidate genes potentially involved in diabetic kidney disease (DKD), we hypothesized that B2M mRNA expression in the urinary sediment could reflect the presence of DKD. Methods. qPCR was used to quantify B2M mRNA expression in cells of the urinary sediment of 51 type 1 diabetes (T1D) patients (61% women, 33.5 [27.0-39.7] years old, with diabetes duration of 21.0 [15.0-28.0] years and HbA1c of 8.2% [7.3-8.9]; median [interquartile interval]) sorted according to the diabetic nephropathy (DN) stages; 8 focal segmental glomerulosclerosis (FSGS) patients and 10 healthy controls. B2M mRNA expression was also evaluated in human embryonic kidney epithelium-like (HEK-293) cells exposed to 25 mM glucose and to albumin in order to mimic, respectively, a diabetic and a proteinuric milieu. Results. No differences were found in B2M mRNA expression among healthy controls, FSGS and T1D patients. Nonetheless B2M mRNA expression was higher in the group composed by T1D patients with incipient or overt DN combined with FSGS patients versus T1D patients without DN combined with healthy controls (P = 0.0007). B2M mRNA expression was higher in T1D patients with incipient or overt DN versus without DN (P = 0.03). B2M mRNA expression positively correlated with albuminuria in the overall T1D population (r = 0.43; P = 0.01) and negatively correlated with estimated glomerular filtration rate in male T1D patients (r = - 0.57; P = 0.01). Increased B2M expression was observed in HEK-293 cells exposed to 25 mM glucose and to albumin. Conclusions. B2M mRNA expression in cells of the urinary sediment is higher in T1D patients with DKD and in patients with FSGS in comparison to healthy subjects, maybe reflecting a tubulointerstitial injury promoted by albumin. Given the proinflammatory nature of B2M, we suggest that this protein contributes to diabetic (and possibly, to non-diabetic) tubulopathy.
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 IMPAIRED HDL-MEDIATED CELL CHOLESTEROL REMOVAL IN ADVANCED BREAST CANCER(2023) SAWADA, M. I.; SANTANA, M.; REIS, M.; ASSIS, S. De; PEREIRA, L.; SANTOS, D.; NUNES, V.; CORREA-GIANNELLA, M. L.; GEBRIM, L. H.; PASSARELLI, M.