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Função renal de pacientes de unidade de terapia intensiva: creatinina plasmática e proteína carreadora do retinol urinário; Renal function of intensive care unit patients: plasma creatinine and urinary retinol-binding protein

MIZOI, Cristina Satoko; DEZOTI, Cassiane; VATTIMO, Maria de Fátima Fernandes
Fonte: Associação de Medicina Intensiva Brasileira - AMIB Publicador: Associação de Medicina Intensiva Brasileira - AMIB
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
96.44%
OBJETIVOS: A avaliação precoce da disfunção renal usando marcadores usuais não supre uma indicação quer da sensitividade e da especificidade da disfunção renal de pacientes críticos. Seriam desejáveis marcadores mais específicos e sensíveis para a detecção precoce de um processo fisiopatológico renal em fase inicial. A proteína carreadora do retinol urinário poderia ser um método alternativo para avaliação precoce da função renal destes pacientes. MÉTODOS: O estudo acompanhou 100 pacientes em terapia intensiva e avaliou suas variáveis clinicas e laboratoriais, incluindo a dosagem de creatinina plasmática e proteina carreadora do retinol urinário e as variáveis demográficas. RESULTADOS: A amostra foi caracterizada por pacientes geriátricos (63,4±15,6 anos), homens (68%), sendo 53% cirúrgicos. Análise estatística mostrou associação entre creatinina plasmática e as seguintes variáveis: gênero (p=0,026), idade (p=0,038), uso de medicação vasoativa (p=0,003), proteinúria (p=0,025), escore Acute Physiological Chronic Health Evaluation (APACHE) II (p=0,000), uréia (p=0,000), potássio (p=0,003) clearance de creatinina estimado (p=0,000). A proteína carreadora do retinol urinário correlacionava-se com outras variáveis: peso usa de ventilação invasiva (p=0...

Influência da resposta inflamatória de fase aguda nos níveis séricos de retinol e da proteína de ligação do retinol em pacientes com AIDS; Influence of acute-phase inflammatory response on serum levels of retinol and retinol binding protein in HIV/AIDS patients

NEVES, Fábio Fernandes; FIGUEIREDO, José Fernando de Castro; JORDÃO JÚNIOR, Alceu Afonso; VANNUCCHI, Hélio
Fonte: Sociedade Brasileira de Medicina Tropical - SBMT Publicador: Sociedade Brasileira de Medicina Tropical - SBMT
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
76.34%
INTRODUÇÃO: a hiporretinolemia constitui fator prognóstico independente em pacientes com AIDS, e a atividade inflamatória causa redução dos níveis séricos deste nutriente na população em geral. Entretanto, faltam estudos que avaliem o impacto da atividade inflamatória sobre o nível sérico do retinol em pacientes com AIDS. MÉTODOS: foram avaliados transversalmente 41 pacientes internados por complicações da AIDS, que tiveram quantificados alguns marcadores de inflamação (proteína C reativa e fator de necrose tumoral alfa) e concentrações séricas de retinol e da proteína de ligação do retinol. RESULTADOS: apesar da baixa (14,6%) prevalência de hiporretinolemia evidenciou-se correlação negativa dos marcadores de inflamação com os níveis séricos de retinol e de sua proteína de ligação nos pacientes com AIDS. CONCLUSÕES: a atividade inflamatória de fase aguda está associada a baixos níveis séricos de retinol em indivíduos com AIDS.; INTRODUCTION: Hyporetinolemia is an independent prognostic factor in AIDS patients. Inflammatory activity causes a reduction in the serum levels of this nutrient in the general population. However, there are no studies assessing the impact of inflammatory activity on the serum retinol level in AIDS patients. METHODS: A cross-sectional assessment was conducted on 41 patients hospitalized due to AIDS complications. Inflammatory markers (C-reactive protein and tumor necrosis factor-alpha) and serum retinol and retinol binding protein concentrations were quantified. RESULTS: Despite the low (14.6%) prevalence of hyporetinolemia...

Novel Zn(2+)-binding Sites in Human Transthyretin IMPLICATIONS FOR AMYLOIDOGENESIS AND RETINOL-BINDING PROTEIN RECOGNITION

PALMIERI, Leonardo de C.; LIMA, Luis Mauricio T. R.; FREIRE, Juliana B. B.; BLEICHER, Lucas; POLIKARPOV, Igor; ALMEIDA, Fabio C. L.; FOGUEL, Debora
Fonte: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC Publicador: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
76.11%
Human transthyretin (TTR) is a homotetrameric protein involved in several amyloidoses. Zn(2+) enhances TTR aggregation in vitro, and is a component of ex vivo TTR amyloid fibrils. We report the first crystal structure of human TTR in complex with Zn(2+) at pH 4.6-7.5. All four structures reveal three tetra-coordinated Zn(2+)-binding sites (ZBS 1-3) per monomer, plus a fourth site (ZBS 4) involving amino acid residues from a symmetry-related tetramer that is not visible in solution by NMR.Zn(2+) binding perturbs loop E-alpha-helix-loop F, the region involved in holo-retinol-binding protein (holo-RBP) recognition, mainly at acidic pH; TTR affinity for holo-RBP decreases similar to 5-fold in the presence of Zn(2+). Interestingly, this same region is disrupted in the crystal structure of the amyloidogenic intermediate of TTR formed at acidic pH in the absence of Zn(2+). HNCO and HNCA experiments performed in solution at pH 7.5 revealed that upon Zn(2+) binding, although the alpha-helix persists, there are perturbations in the resonances of the residues that flank this region, suggesting an increase in structural flexibility. While stability of the monomer of TTR decreases in the presence of Zn(2+), which is consistent with the tertiary structural perturbation provoked by Zn(2+) binding...

Retinol binding protein 4 and retinol in steatotic and nonsteatotic rat livers in the setting of partial hepatectomy under ischemia/reperfusion

Elias-Miro, Maria; Massip-Salcedo, Marta; Raila, Jens; Schweigert, Florian; Mendes-Braz, Mariana; Ramalho, Fernando; Jimenez-Castro, Monica B.; Casillas-Ramirez, Arani; Bermudo, Raquel; Rimola, Antoni; Rodes, Juan; Peralta, Carmen
Fonte: WILEY-BLACKWELL; HOBOKEN Publicador: WILEY-BLACKWELL; HOBOKEN
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
96.32%
Steatotic livers show increased hepatic damage and impaired regeneration after partial hepatectomy (PH) under ischemia/reperfusion (I/R), which is commonly applied in clinical practice to reduce bleeding. The known function of retinol-binding protein 4 (RBP4) is to transport retinol in the circulation. We examined whether modulating RBP4 and/or retinol could protect steatotic and nonsteatotic livers in the setting of PH under I/R. Steatotic and nonsteatotic livers from Zucker rats were subjected to PH (70%) with 60 minutes of ischemia. RBP4 and retinol levels were measured and altered pharmacologically, and their effects on hepatic damage and regeneration were studied after reperfusion. Decreased RBP4 levels were observed in both liver types, whereas retinol levels were reduced only in steatotic livers. RBP4 administration exacerbated the negative consequences of liver surgery with respect to damage and liver regeneration in both liver types. RBP4 affected the mobilization of retinol from steatotic livers, and this revealed actions of RBP4 independent of simple retinol transport. The injurious effects of RBP4 were not due to changes in retinol levels. Treatment with retinol was effective only for steatotic livers. Indeed, retinol increased hepatic injury and impaired liver regeneration in nonsteatotic livers. In steatotic livers...

Função renal de pacientes de Unidade de Terapia Intensiva: creatinina plasmática e proteína carreadora do retinol urinário (RBPu).; Renal function of intensive care unit patients: plasma creatinine and urinary retinol-binding protein (uRBP).

Hokama, Cristina Satoko Mizoi
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: dissertação de mestrado Formato: application/pdf
Publicado em 26/08/2004 Português
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96.23%
A avaliação da disfunção renal pelos marcadores usuais não tem determinado impacto na redução da incidência da insuficiência renal aguda (IRA) nos pacientes de terapia intensiva. Este estudo avaliou 100 pacientes admitidos em uma unidade de terapia intensiva (UTI) quanto às características demográficas; a relação entre creatinina plasmática e proteína carreadora do retinol (RBPu) e as variáveis clínico-laboratoriais; e a sensibilidade e a especificidade da RBPu. A amostra caracterizou-se como geriátrica (63,4±15,6 anos), do sexo masculino (68%), 47% dos pacientes tiveram tratamento clínico e 53% cirúrgico. A coleta de dados foi realizada no período de 13,9±8,3 horas após a admissão na UTI. A análise dos resultados mostrou associação entre a creatinina plasmática e as variáveis: gênero (p-0,026), idade (p-0,038), uso de droga vasoativa (p-0,003), proteínúria (p-0,025), APACHE II (p-0,000), uréia (p-0,000), potássio (p-0,003) e clearance de creatinina estimado (p-0,000). A RBPu mostrou associação com um número maior de variáveis: peso (IMC), uso de ventilação invasiva (p-0,000), uso de antiinflamatório não-hormonal (p-0,018), uso de droga vasoativa (p-0,021), temperatura > 37,5ºC (p-0,005)...

Plasma levels of transthyretin and retinol-binding protein in child-a cirrhotic patients in relation to protein-calorie status and plasma amino acids, zinc, vitamin a and plasma thyroid hormones

Calamita, Zamir; Dichi, Isaías; Papini-Berto, Sílvia J.; Dichi, Jane B.; Angeleli, Aparecida Y.O.; Vannucchi, Hélio; Caramori, Carlos; Burini, Roberto Carlos
Tipo: Artigo de Revista Científica Formato: 139-147
Português
Relevância na Pesquisa
96.34%
Transthyretin and retinal-binding protein are sensitive markers of acute protein-calorie malnutrition both for early diagnosis and dietary evaluation. A preliminary study showed that retinal-binding protein is the most sensitive marker of protein-calorie malnutrition in cirrhotic patients, even those with the mild form of the disease (Child A). However, in addition to being affected by protein-calorie malnutrition, the levels of these short half-life-liver-produced proteins are also influenced by other factors of a nutritional (zinc, tryptophan, vitamin A, etc) and non-nutritional (sex, aging, hormones, renal and liver functions and inflammatory activity) nature. These interactions were investigated in 11 adult male patients (49.9 ± 9.2 years of age) with alcoholic cirrhosis (Child-Pugh grade A) and with normal renal function. Both transthyretin and retinol binding protein were reduced below normal levels in 55% of the patients, in close agreement with their plasma levels of retinal. In 67% of the patients (4/6), the reduced levels of transthyretin and retinal-binding protein were caused by altered liver function and in 50% (3/6) they were caused by protein-calorie malnutrition. Thus, the present data, taken as a whole, indicate that reduced transthyretin and retinal-binding protein levels in mild cirrhosis of the liver are mainly due to liver failure and/or vitamin A status rather than representing an isolated protein-calorie malnutrition indicator.

Serum retinol binding protein 4 is not decreased in congenital generalized lipodystrophy: a case series

Godoy-Matos,Amélio F.; Moreira,Rodrigo O.; MacDowell,Renata; Bendet,Izidro
Fonte: Sociedade Brasileira de Endocrinologia e Metabologia Publicador: Sociedade Brasileira de Endocrinologia e Metabologia
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/06/2011 Português
Relevância na Pesquisa
96.14%
INTRODUCTION: Previous studies have suggested that Retinol Binding Protein 4 (RPB4), a protein produced by the adipose tissue, is associated with insulin resistance (IR). Congenital Generalized Lipodystrophy (CGL) is a rare disease characterized by IR and paucity of adipose tissue. Our objective was to determine RBP4 levels in patients with CGL. SUBJECTS AND METHODS: Six (6) patients with CGL and a healthy control group were selected to participate in the study. Anthropometric and biochemical variables were compared between groups. RESULTS: No difference was observed in RBP4 levels between the two groups (CGL 42.5 [12.5 - 127] vs. control 57.4 [15.9 - 165]; p = 0.78). On the other hand, leptin levels were significantly lower in CGL patients (CGL 0.65 [0.2 - 0.7] vs. control 10.9 [0.9 - 38.6]; p = 0.015). No correlation was found between RBP-4 and waist circunference (r = 0.18, p = 0.57), or BMI (r = 0.24, p = 0.45). CONCLUSION: RBP4 is not decreased in CGL. These results suggest that adipose tissue may not be the main source of RBP4.

Determination of renal function in long-term heart transplant patients by measurement of urinary retinol-binding protein levels

Chinen,R.; Câmara,N.O.S.; Nishida,S.; Silva,M.S.; Rodrigues,D.A.; Pereira,A.B.; Pacheco-Silva,A.
Fonte: Associação Brasileira de Divulgação Científica Publicador: Associação Brasileira de Divulgação Científica
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/10/2006 Português
Relevância na Pesquisa
96.13%
Significant improvements have been noted in heart transplantation with the advent of cyclosporine. However, cyclosporine use is associated with significant side effects, such as chronic renal failure. We were interested in evaluating the incidence of long-term renal dysfunction in heart transplant recipients. Fifty-three heart transplant recipients were enrolled in the study. Forty-three patients completed the entire evaluation and follow-up. Glomerular (serum creatinine, creatinine clearance measured, and creatinine clearance calculated) and tubular functions (urinary retinol-binding protein, uRBP) were re-analyzed after 18 months. At the enrollment time, the prevalence of renal failure ranged from 37.7 to 54% according to criteria used to define it (serum creatinine > or = 1.5 mg/dL and creatinine clearance

Interaction between estrogen receptor and retinol-binding protein-4 polymorphisms as a tool for the selection of prolific pigs

Gonçalves,Iara Denise Vasconcellos; Gonçalves,Paulo Bayard Dias; Silva,Janandra Cortese da; Portela Jr,Valério Valdetar; Borges,Luiz Felipe Kruel; Oliveira,João Francisco Coelho; Lovatto,Paulo Alberto
Fonte: Sociedade Brasileira de Genética Publicador: Sociedade Brasileira de Genética
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/2008 Português
Relevância na Pesquisa
96.13%
The aim of the present study was to investigate the association of the estrogen receptor (ER-PvuII) and retinol-binding protein 4 (RBP4-MspI) gene polymorphisms and their interactions with prolificacy in a commercial synthetic pig line reared in Brazil. A total of 10,374 piglet records from 218 sows and 817 litters were used for litter size analysis. Only females with three or four farrowings were included in the analysis. The mean litter size ranged from 5.0 to 19.5 piglets. DNA was extracted from leukocytes by a standard method, and ER-PvuII and RBP4-MspI polymorphisms were characterized by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The association between alleles or genotypes and reproductive performance was analyzed using a general linear model including the interaction between the ER-PvuII and RBP4-MspI genotypes. For the ER-PvuII gene, the allele frequencies of allele A and allele B were 0.56 and 0.44, respectively. For the RBP4-MspI gene, the frequencies of alleles A1 and A2 were 0.29 and 0.71, respectively. The total number of piglets born (TNB), born alive (NBA), or number of mummies and stillborn piglets (NMUM and NSB) per litter did not differ between the various ER-PvuII and RBP4-MspI genotypes. However...

Localization of cellular retinol-binding protein and retinol-binding protein in cells comprising the blood-brain barrier of rat and human.

MacDonald, P N; Bok, D; Ong, D E
Tipo: text
Publicado em /06/1990 Português
Relevância na Pesquisa
66.32%
Brain is not generally recognized as an organ that requires vitamin A, perhaps because no obvious histologic lesions have been observed in severely vitamin A-deficient animals. However, brain tissue does contain cellular vitamin A-binding proteins and a nuclear receptor protein for retinoic acid. In the present study, immunohistochemical techniques were used to determine the cell-specific location of cellular retinol-binding protein in human and rat brain tissue. Cellular retinol-binding protein was localized specifically within the endothelial cells of the brain microvasculature and within the cuboidal epithelial cells of the choroid plexus, two primary sites of the mammalian blood-brain barrier. In addition, autoradiographic procedures demonstrated binding sites for serum retinol-binding protein in the choroidal epithelium. These observations suggest that a significant movement of retinol across the blood-brain barrier may occur.

Retinol-binding protein: the transport protein for vitamin A in human plasma

Kanai, Masamitsu; Raz, Amiram; Goodman, DeWitt S.
Tipo: text
Publicado em /09/1968 Português
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66.34%
Vitamin A circulates in human plasma as retinol bound to a specific transport protein. This protein differs from the known low and high density plasma lipoproteins and has a hydrated density greater than 1.21. In order to study this protein, volunteers were injected intravenously with retinol-15-14C. Plasma was collected 1-3 days later, and the purification of retinol-binding protein (RBP) was monitored by assaying for 14C and also by following the fluorescence of the protein-bound retinol. Purification of RBP was effected by the sequence: Cohn fractionation, chromatography on columns of Sephadex G-200 and diethylaminoethyl (DEAE)-Sephadex, preparative polyacrylamide gel electrophoresis, and finally chromatography on Sephadex G-100. These procedures resulted in a preparation of RBP which was at least 98% pure and which had been purified more than 1500-fold. Purified RBP has ?1 mobility on electrophoresis and has a molecular weight of approximately 21,000-22,000. There appears to be one binding site for retinol per molecule of RBP. Solutions of RBP are fluorescent (characteristic of retinol) and have ultraviolet absorption spectra with peaks at 330 m? (resulting from the bound retinol) and at 280 m?. There are no fatty acid or fatty acyl chains present in purified RBP. The usual concentration of RBP in plasma is of the order of 3-4 mg/100 ml. In plasma...

Cellular retinol-binding protein allows specific interaction of retinol with the nucleus in vitro.

Takase, S; Ong, D E; Chytil, F
Tipo: text
Publicado em /05/1979 Português
Relevância na Pesquisa
66.35%
Purified cellular retinol-binding protein (CRBP), a potential mediator of vitamin A action, was found to enable retinol to bind in a specific manner to isolated nuclei from livers of vitamin A deficient rats. Binding was followed after complexing [3H]retinol with CRBP. The binding was specific, saturable, and temperature dependent. CRBP charged with unlabeled retinol or CRBP without retinol diminished binding of radioactivity whereas free retinol did not. No specific binding sites could be detected for free retinol. Purified cellular retinoic acid binding protein (CRABI) complexed with retinoic acid did not diminish the amount of retinol bound to nuclei. Approximately 3 x 10(5) specific binding sites per nucleus could be detected. Fewer binding sites were found in nuclei isolated from livers of control (chow-fed) rats and also from livers of vitamin A-deficient rats 2 hr after refeeding with retinylacetate.

Retinol-binding protein and transthyretin mRNA levels in visceral yolk sac and liver during fetal development in the rat.

Soprano, D R; Soprano, K J; Goodman, D S
Tipo: text
Publicado em /10/1986 Português
Relevância na Pesquisa
66.43%
Studies were conducted to explore the synthesis of retinol-binding protein and transthyretin by embryonic and extraembryonic tissues during fetal development in the rat. The levels of retinol-binding protein mRNA and transthyretin mRNA were measured in fetal liver and in extraembryonic tissues by RNA gel blot analysis and hybridization with specific cDNA probes. Retinol-binding protein mRNA and transthyretin mRNA were both detected in the liver of fetuses at 14 days of gestation. The relative levels of these two transcripts increased during later fetal development; by the 20th day of gestation retinol-binding protein mRNA levels were comparable to those of the adult liver, while the levels of transthyretin mRNA were only 46% of those of the adult liver. Examination of the extraembryonic membranes for retinol-binding protein mRNA and transthyretin mRNA showed that these two transcripts were present specifically and only in the visceral yolk sac. The relative levels of retinol-binding protein mRNA and transthyretin mRNA in visceral yolk sac were constant from 14 to 20 days of gestation, averaging 58% and 51%, respectively, of the adult liver levels of these two transcripts. Both retinol-binding protein mRNA and transthyretin mRNA in the visceral yolk sac were found to be specifically localized in the endodermal layer. Finally...

Structure-function studies on human retinol-binding protein using site-directed mutagenesis.

Sivaprasadarao, A; Findlay, J B
Tipo: text
Publicado em 01/06/1994 Português
Relevância na Pesquisa
66.37%
Retinol-binding protein (RBP) transports vitamin A in the plasma. It consists of eight anti-parallel beta-strands (A to H) that fold to form an orthogonal barrel. The loops connecting the strands A and B, C and D, and E and F form the entrance to the binding site in the barrel. The retinol molecule is found deep inside this barrel. Apart from its specific interaction with retinol, RBP is involved in two other molecular-recognition properties, that is it binds to transthyretin (TTR), another serum protein, and to a cell-surface receptor. Using site-directed mutagenesis, specific changes were made to the loop regions of human RBP and the resultant mutant proteins were tested for their ability to bind to retinol, to TTR and to the RBP receptor. While all the variants retained their ability to bind retinol, that in which residues 92 to 98 of the loop E-F were deleted completely lost its ability to interact with TTR, but retained some binding activity for the receptor. In contrast, the double mutant in which leucine residues at positions 63 and 64 of the loop C-D were changed to arginine and serine respectively partially retained its TTR-binding ability, but completely lost its affinity for the RBP receptor. Mutation of Leu-35 of loop A-B to valine revealed no apparent effect on any of the binding activities of RBP. However...

Specific interaction of ivermectin with retinol-binding protein from filarial parasites.

Sani, B P; Vaid, A
Tipo: text
Publicado em 01/02/1988 Português
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66.37%
Specific cellular binding proteins for retinol and retinoic acid from mammalian and avian species may mediate the action of retinoids in the control of epithelial differentiation, growth and tumorigenesis. Parasite retinol-binding protein (PRBP) and parasite retinoic acid-binding protein (PRABP) isolated and characterized from parasitic worms of the family Filarioidea might be involved in some possible action of vitamin A compounds in these parasites. Ivermectin, a potent and widely used anti-parasitic drug, competes efficiently with retinol for retinol-binding sites on PRBP, but not for the host-tissue retinol-binding-protein sites. The drug has no affinity for retinoic acid-binding proteins from either parasite or host tissues. Binding studies using radiolabelled ivermectin and retinol reveal that ivermectin has a higher affinity than retinol for PRBP. A correlation exists between the binding affinities of ivermectin analogues and their anti-parasitic activities. A binding-protein-mediated interrelationship may exist between the actions of retinol and ivermectin in the parasites, but not in the host tissues.

Novel Zn2+-binding Sites in Human Transthyretin: IMPLICATIONS FOR AMYLOIDOGENESIS AND RETINOL-BINDING PROTEIN RECOGNITION*

de C. Palmieri, Leonardo; Lima, Luis Mauricio T. R.; Freire, Juliana B. B.; Bleicher, Lucas; Polikarpov, Igor; Almeida, Fabio C. L.; Foguel, Debora
Fonte: American Society for Biochemistry and Molecular Biology Publicador: American Society for Biochemistry and Molecular Biology
Tipo: text
Português
Relevância na Pesquisa
76.12%
Human transthyretin (TTR) is a homotetrameric protein involved in several amyloidoses. Zn2+ enhances TTR aggregation in vitro, and is a component of ex vivo TTR amyloid fibrils. We report the first crystal structure of human TTR in complex with Zn2+ at pH 4.6–7.5. All four structures reveal three tetra-coordinated Zn2+-binding sites (ZBS 1–3) per monomer, plus a fourth site (ZBS 4) involving amino acid residues from a symmetry-related tetramer that is not visible in solution by NMR. Zn2+ binding perturbs loop E-?-helix-loop F, the region involved in holo-retinol-binding protein (holo-RBP) recognition, mainly at acidic pH; TTR affinity for holo-RBP decreases ?5-fold in the presence of Zn2+. Interestingly, this same region is disrupted in the crystal structure of the amyloidogenic intermediate of TTR formed at acidic pH in the absence of Zn2+. HNCO and HNCA experiments performed in solution at pH 7.5 revealed that upon Zn2+ binding, although the ?-helix persists, there are perturbations in the resonances of the residues that flank this region, suggesting an increase in structural flexibility. While stability of the monomer of TTR decreases in the presence of Zn2+, which is consistent with the tertiary structural perturbation provoked by Zn2+ binding...

Retinol-Binding Protein 4 Inhibits Insulin Signaling in Adipocytes by Inducing Proinflammatory Cytokines in Macrophages through a c-Jun N-Terminal Kinase- and Toll-Like Receptor 4-Dependent and Retinol-Independent Mechanism

Norseen, Julie; Hosooka, Tetsuya; Hammarstedt, Ann; Yore, Mark M.; Kant, Shashi; Aryal, Pratik; Kiernan, Urban A.; Phillips, David A.; Maruyama, Hiroshi; Kraus, Bettina J.; Usheva, Anny; Davis, Roger J.; Smith, Ulf; Kahn, Barbara B.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: text
Publicado em /05/2012 Português
Relevância na Pesquisa
66.3%
Retinol-binding protein 4 (RBP4), the sole retinol transporter in blood, is secreted from adipocytes and liver. Serum RBP4 levels correlate highly with insulin resistance, other metabolic syndrome factors, and cardiovascular disease. Elevated serum RBP4 causes insulin resistance, but the molecular mechanisms are unknown. Here we show that RBP4 induces expression of proinflammatory cytokines in mouse and human macrophages and thereby indirectly inhibits insulin signaling in cocultured adipocytes. This occurs through activation of c-Jun N-terminal protein kinase (JNK) and Toll-like receptor 4 (TLR4) pathways independent of the RBP4 receptor, STRA6. RBP4 effects are markedly attenuated in JNK1?/? JNK2?/? macrophages and TLR4?/? macrophages. Because RBP4 is a retinol-binding protein, we investigated whether these effects are retinol dependent. Unexpectedly, retinol-free RBP4 (apo-RBP4) is as potent as retinol-bound RBP4 (holo-RBP4) in inducing proinflammatory cytokines in macrophages. Apo-RBP4 is likely to be physiologically significant since RBP4/retinol ratios are increased in serum of lean and obese insulin-resistant humans compared to ratios in insulin-sensitive humans, indicating that higher apo-RBP4 is associated with insulin resistance independent of obesity. Thus...

The retinol esterifying enzyme LRAT supports cell signaling by retinol-binding protein and its receptor STRA6

Marwarha, Gurdeep; Berry, Daniel C.; Croniger, Colleen M.; Noy, Noa
Fonte: Federation of American Societies for Experimental Biology Publicador: Federation of American Societies for Experimental Biology
Tipo: text
Publicado em /01/2014 Português
Relevância na Pesquisa
66.34%
Vitamin A, retinol, circulates in blood bound to retinol-binding protein (RBP). At some tissues, holo-RBP is recognized by a plasma membrane receptor termed STRA6, which serves a dual role: it mediates transport of retinol from RBP into cells, and it functions as a cytokine receptor that, on binding holo-RBP, activates JAK2/STAT5 signaling. As STAT target genes include SOCS3, an inhibitor of insulin receptor, holo-RBP suppresses insulin responses in STRA6-expressing cells. We have shown previously that the two functions of STRA6 are interdependent. These observations suggest factors that regulate STRA6-mediated retinol transport may also control STRA6-mediated cell signaling. One such factor is retinol metabolism, which enables cellular uptake of retinol by maintaining an inward-directed concentration gradient. We show here that lecithin:retinol acyl transferase (LRAT), which catalyzes esterification of retinol to its storage species retinyl esters, is necessary for activation of the STRA6/JAK2/STAT5 cascade by holo-RBP. In accordance, LRAT-null mice are protected from holo-RBP-induced suppression of insulin responses. Hence, STRA6 signaling, which requires STRA6-mediated retinol transport, is supported by LRAT-catalyzed retinol metabolism. The observations demonstrate that STRA6 regulates key cellular processes by coupling circulating holo-RBP levels and intracellular retinol metabolism to cell signaling.—Marwarha...

Associations between retinol-binding protein 4 and cardiometabolic risk factors and subclinical atherosclerosis in recently postmenopausal women: cross-sectional analyses from the KEEPS study

Huang, Gary; Wang, Dan; Khan, Unab I; Zeb, Irfan; Manson, JoAnn Elisabeth; Miller, Virginia; Hodis, Howard N; Budoff, Matthew J; Merriam, George R; Harman, Mitchell S; Brinton, Eliot A; Cedars, Marcelle I; Su, Yali; Lobo, Rogerio A; Naftolin, Frederick; S
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
Português
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96.14%
Background: The published literature regarding the relationships between retinol-binding protein 4 (RBP4) and cardiometabolic risk factors and subclinical atherosclerosis is conflicting, likely due, in part, to limitations of frequently used RBP4 assays. Prior large studies have not utilized the gold-standard western blot analysis of RBP4 levels. Methods: Full-length serum RBP4 levels were measured by western blot in 709 postmenopausal women screened for the Kronos Early Estrogen Prevention Study. Cross-sectional analyses related RBP4 levels to cardiometabolic risk factors, carotid artery intima-media thickness (CIMT), and coronary artery calcification (CAC). Results: The mean age of women was 52.9 (± 2.6) years, and the median RBP4 level was 49.0 (interquartile range 36.9-61.5) ?g/mL. Higher RBP4 levels were weakly associated with higher triglycerides (age, race, and smoking-adjusted partial Spearman correlation coefficient = 0.10; P = 0.01), but were unrelated to blood pressure, cholesterol, C-reactive protein, glucose, insulin, and CIMT levels (all partial Spearman correlation coefficients ?0.06, P > 0.05). Results suggested a curvilinear association between RBP4 levels and CAC, with women in the bottom and upper quartiles of RBP4 having higher odds of CAC (odds ratio [95% confidence interval] 2.10 [1.07-4.09]...

Retinol binding protein 4 promotes hyperinsulinism-induced proliferation of rat aortic smooth muscle cells

LI, FEI; XIA, KE; SHEIKH, MD SAYED ALI; CHENG, JINFANG; LI, CHUANCHANG; YANG, TIANLUN
Fonte: D.A. Spandidos Publicador: D.A. Spandidos
Tipo: Artigo de Revista Científica
Português
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Recent studies have suggested that retinol binding protein 4 (RBP4), an adipocytokine related to insulin resistance (IR), may play an important role in the development of atherosclerosis and cardiovascular diseases (CVD). Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) is one of the most common causes of atherosclerosis. Hyperinsulinism promotes proliferation of VSMCs through the MAPK pathway. However, whether RBP4 is involved in insulin-induced proliferation of VSMCs leading to atherosclerosis remains unclear. In the present study, we evaluated the role of RBP4 and the potential relevance of signaling pathways in this process. Different concentrations of RBP4 (1 and 4 ?g/ml) were added to rat aortic smooth muscle cells (RASMCs) during insulin-induced proliferation. The levels of cell growth signaling pathway proteins ERK1/2, p-ERK1/2, JAK2, p-JAK2, STAT3 and p-STAT3 were assessed by western blotting in order to identify the pathway(s) that are activated during insulin-induced proliferation. The specific inhibitors of ERK1/2 (PD98059) and JAK2 (AG490) were used to confirm our findings. Insulin induced proliferation of RASMCs in a concentration- and time-dependent manner, and increased the expression of ERK1/2...