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1.
Br J Nutr ; 101 Suppl 1: S1-45, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19586558

RESUMO

Inflammation is a stereotypical physiological response to infections and tissue injury; it initiates pathogen killing as well as tissue repair processes and helps to restore homeostasis at infected or damaged sites. Acute inflammatory reactions are usually self-limiting and resolve rapidly, due to the involvement of negative feedback mechanisms. Thus, regulated inflammatory responses are essential to remain healthy and maintain homeostasis. However, inflammatory responses that fail to regulate themselves can become chronic and contribute to the perpetuation and progression of disease. Characteristics typical of chronic inflammatory responses underlying the pathophysiology of several disorders include loss of barrier function, responsiveness to a normally benign stimulus, infiltration of inflammatory cells into compartments where they are not normally found in such high numbers, and overproduction of oxidants, cytokines, chemokines, eicosanoids and matrix metalloproteinases. The levels of these mediators amplify the inflammatory response, are destructive and contribute to the clinical symptoms. Various dietary components including long chain omega-3 fatty acids, antioxidant vitamins, plant flavonoids, prebiotics and probiotics have the potential to modulate predisposition to chronic inflammatory conditions and may have a role in their therapy. These components act through a variety of mechanisms including decreasing inflammatory mediator production through effects on cell signaling and gene expression (omega-3 fatty acids, vitamin E, plant flavonoids), reducing the production of damaging oxidants (vitamin E and other antioxidants), and promoting gut barrier function and anti-inflammatory responses (prebiotics and probiotics). However, in general really strong evidence of benefit to human health through anti-inflammatory actions is lacking for most of these dietary components. Thus, further studies addressing efficacy in humans linked to studies providing greater understanding of the mechanisms of action involved are required.


Assuntos
Inflamação/fisiopatologia , Fenômenos Fisiológicos da Nutrição/fisiologia , Artrite Reumatoide/dietoterapia , Artrite Reumatoide/fisiopatologia , Doenças Cardiovasculares/dietoterapia , Doenças Cardiovasculares/fisiopatologia , Doença Celíaca/dietoterapia , Doença Celíaca/fisiopatologia , Humanos , Inflamação/dietoterapia , Doenças Inflamatórias Intestinais/dietoterapia , Doenças Inflamatórias Intestinais/fisiopatologia , Obesidade/dietoterapia , Obesidade/fisiopatologia , Hipersensibilidade Respiratória/dietoterapia , Hipersensibilidade Respiratória/fisiopatologia , Dermatopatias/dietoterapia , Dermatopatias/fisiopatologia
2.
Allergy ; 64(3): 484-7, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18507650

RESUMO

BACKGROUND: It has been suggested that human breast milk oligosaccharides play a role in the development of the immune system in infants, and may consequently inhibit the onset of allergy. A specific prebiotic mixture of short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides (GOS/FOS) has been shown to reduce the incidence of atopic dermatitis (AD) at 6 months of age in infants at risk for allergy. AIM OF THE STUDY: This study was aimed to analyze the effect of GOS/FOS on the immune response in these infants. METHODS: In a double-blind randomized placebo-controlled study, infants received a hypoallergenic whey formula with either 8 g/l GOS/FOS in a 9 : 1 ratio (IMMUNOFORTIS) or 8 g/l maltodextrine (placebo) for 6 months. At 3 months of age, children were vaccinated with Hexavac against a.o. diphteria, tetanus, polio (DTP). At 6 months of age, plasma samples were collected from 84 infants (verum group n = 41, placebo group n = 43). Levels of total immunoglobulins (Ig) and of cow's milk protein (CMP-) and DTP-specific Ig were measured. RESULTS: GOS/FOS supplementation led to a significant reduction in the plasma level of total IgE, IgG1, IgG2 and IgG3, whereas no effect on IgG4 was observed. CMP-specific IgG1 was significantly decreased. DTP-specific Ig levels were not affected. CONCLUSIONS: This study shows that GOS/FOS supplementation induces a beneficial antibody profile. GOS/FOS reduces the total Ig response and modulates the immune response towards CMP, while leaving the response to vaccination intact. This suggests that oral GOS/FOS supplementation is a safe method to restrain the atopic march.


Assuntos
Dermatite Atópica/prevenção & controle , Fórmulas Infantis/química , Oligossacarídeos/uso terapêutico , Alérgenos/imunologia , Animais , Dermatite Atópica/imunologia , Método Duplo-Cego , Ensaio de Imunoadsorção Enzimática , Humanos , Hipersensibilidade/imunologia , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Lactente , Leite/imunologia , Leite Humano/química , Oligossacarídeos/imunologia , Fatores de Risco
3.
Int Immunopharmacol ; 7(12): 1582-7, 2007 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-17920536

RESUMO

Specific mixtures of prebiotic oligosaccharides showed immune modulatory effects in previous murine vaccination experiments, suggesting a shift towards T-helper 1 (Th1) immunity. These mixtures consisted of short-chain galacto-oligosaccharides (scGOS) and long-chain fructo-oligosaccharides (lcFOS) in a 9:1 ratio (Immunofortis), with or without pectin-derived acidic oligosaccharides (pAOS). To investigate whether these mixtures could suppress Th2-related responses, they were tested in an ovalbumin (OVA)-induced model for experimental allergic asthma in BALB/c mice. Supplementation with two mixtures of scGOS/lcFOS and scGOS/lcFOS/pAOS at approximately 1% (w/w% net oligosaccharides) in the diet, starting two weeks before OVA sensitization and lasting until the end of the experiment, decreased of several parameters of allergic asthma. The OVA-induced airway inflammation and hyperresponsiveness was significantly suppressed by both mixtures. Moreover, OVA-specific IgE titers were decreased by more than 25%, although this effect was not significant. The effects of the oligosaccharide mixture with pAOS appeared to be more pronounced than the effects of the scGOS/lcFOS mixture without pAOS, but a direct comparison between the mixtures was not made. Overall, the results further support the hypothesis that specific mixtures of oligosaccharides modulate the Th1/Th2 balance by enhancing Th1-related and suppressing Th2-related parameters.


Assuntos
Asma/prevenção & controle , Carboidratos da Dieta/farmacologia , Suplementos Nutricionais , Oligossacarídeos/farmacologia , Animais , Asma/sangue , Asma/imunologia , Testes de Provocação Brônquica , Líquido da Lavagem Broncoalveolar/citologia , Contagem de Células , Carboidratos da Dieta/administração & dosagem , Frutanos/administração & dosagem , Frutanos/farmacologia , Galactanos/administração & dosagem , Galactanos/farmacologia , Imunização , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/farmacologia , Pulmão/efeitos dos fármacos , Pulmão/fisiopatologia , Masculino , Cloreto de Metacolina/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Oligossacarídeos/administração & dosagem , Ovalbumina/imunologia , Pectinas/química , Pectinas/farmacologia , Hipersensibilidade Respiratória/induzido quimicamente , Hipersensibilidade Respiratória/fisiopatologia , Hipersensibilidade Respiratória/prevenção & controle
4.
Crit Rev Immunol ; 27(2): 97-140, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17725499

RESUMO

Orally applied nondigestible carbohydrates (NDC) have been associated with immune-modulating effects and other health benefits. The effects of prebiotic carbohydrates have recently received much attention, but other NDC have been reported to induce immune modulation as well. Many different effects have been shown on parameters of innate and specific immunity, mostly in animal experiments or in vitro. Data from clinical trials are limited, but promising studies have reported beneficial effects on mucosal and systemic immunity in humans. NDC are fermented to various degrees by the intestinal microbiota. Therefore, immune-modulatory properties have often been attributed to microbiota-dependent effects, especially in the case of prebiotic NDC. However, some NDC have been reported to bind to specific receptors on cells of the immune system, suggesting microbiota-independent, immune-modulatory effects play a role as well. This review aims to provide an overview of the published immune-modulatory effects in vitro and in vivo induced by NDC such as fructans, galactooligosaccharides, beta-glucans, pectins, and resistant starch. In addition, issues related to the underlying mechanisms are discussed: interaction between bacteria, their metabolites and the immune system, as well as direct effects of NDC via lectin receptors.


Assuntos
Carboidratos/fisiologia , Fibras na Dieta , Suplementos Nutricionais , Fatores Imunológicos/fisiologia , Animais , Humanos
5.
Clin Exp Allergy ; 36(3): 303-10, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16499640

RESUMO

BACKGROUND: One to two percent of infants suffer from IgE-mediated allergic reactions against cow's milk proteins. Most children develop clinical tolerance, but approximately 15% are still allergic by the age of 10 years. Little is known about the T cell epitopes in individual cow's milk protein in relation to allergy and tolerance. OBJECTIVE: To identify T cell epitopes in alphas1-casein, the most abundant milk protein, and to investigate T cell responses toward these epitopes in allergic, atopic and non-atopic children. METHODS: Allergen-specific T cell lines (TCLs) were derived from peripheral blood mononuclear cells of 11 cow's milk allergic, nine atopic and nine non-atopic children. T cell responses were measured to alphas1-casein and to overlapping peptides (18-mers), spanning the alphas1-casein molecule. Proliferation was determined by incorporation of (3)H-thymidine, and cytokine production (IL-10, IL-13 and IFN-gamma) was measured by ELISA. RESULTS: Four main regions (amino acid (AA) residues 43-66, 73-96, 91-114 and 127-180) in the alphas1-casein molecule were immunogenic to T cells, among which the AA residues 133-156 spanned the immunodominant part. Only subtle differences were found in peptide recognition between the subject groups. Some of the peptides induced slightly Th1- or Th2-skewed cytokine responses. The increased levels of IL-10 in response to alphas1-casein observed in TCLs from atopic children appeared not to be linked to recognition of specific IL-10-inducing epitopes. CONCLUSIONS: The immunodominant sequence in alphas1-casein is spanned by AA residues 133-156. Tolerance towards alphas1-casein in atopic children may be mediated by an overall induction of IL-10 and not by recognition of certain T cell epitopes. The identified T cell epitopes in children with cow's milk allergy may be useful targets in developing peptide immunotherapy.


Assuntos
Caseínas/imunologia , Epitopos de Linfócito T/imunologia , Hipersensibilidade a Leite/imunologia , Adolescente , Sequência de Aminoácidos , Animais , Caseínas/genética , Linhagem Celular , Proliferação de Células , Criança , Pré-Escolar , Citocinas/biossíntese , Método Duplo-Cego , Humanos , Hipersensibilidade Imediata/imunologia , Tolerância Imunológica , Epitopos Imunodominantes/imunologia , Lactente , Ativação Linfocitária/imunologia , Leite/imunologia , Dados de Sequência Molecular , Fragmentos de Peptídeos/imunologia , Linfócitos T/imunologia
7.
Support Care Cancer ; 12(4): 227-33, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-14752625

RESUMO

We scored oral mucositis and gut toxicity and measured sugar permeability testing among 56 recipients of a haematopoietic stem cell transplant (HSCT) given myeloablative conditioning with idarubicin, cyclophosphamide and TBI, and a group of 18 patients given cytotoxic chemotherapy for newly diagnosed acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS). Gut integrity was already disturbed in the AML/MDS group as measured by the lactulose/rhamnose ratio (L/R ratio=0.09) before therapy and was severely perturbed (L/R ratio >0.13) for a month after HSCT. Oral mucositis and to a lesser extent gut toxicity was only significantly correlated with disturbed permeability in the transplant group. The data suggest that sugar permeability, oral mucositis and gut toxicity measure different features of mucosal damage after intensive cytotoxic therapy.


Assuntos
Antineoplásicos/efeitos adversos , Mucosa Gástrica/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Bucal/efeitos dos fármacos , Condicionamento Pré-Transplante/efeitos adversos , 3-O-Metilglucose/farmacocinética , Doença Aguda , Adulto , Antibióticos Antineoplásicos/efeitos adversos , Antineoplásicos Alquilantes/efeitos adversos , Ciclofosfamida/efeitos adversos , Feminino , Mucosa Gástrica/efeitos da radiação , Transplante de Células-Tronco Hematopoéticas , Humanos , Idarubicina/efeitos adversos , Mucosa Intestinal/efeitos da radiação , Lactulose/farmacocinética , Leucemia Mieloide/terapia , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/efeitos da radiação , Síndromes Mielodisplásicas/terapia , Permeabilidade , Ramnose/farmacocinética , Estomatite/induzido quimicamente , Estomatite/etiologia , Irradiação Corporal Total , Xilose/farmacocinética
8.
Leukemia ; 18(2): 276-84, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-14671640

RESUMO

The inhibition of nuclear factor kappa B (NF-kappaB) by, for instance, curcumin is becoming an important new approach in combination with chemotherapy or irradiation for the treatment of a variety of cancers including haematological malignancies. A dose-limiting side effect of anticancer therapy in the gastrointestinal tract is mucosal barrier injury. It is hypothesised that mucosal barrier injury is initiated and amplified by proinflammatory-and NF-kappaB-regulated mediators. Therefore, the effect of NF-kappaB inhibition was studied in the onset of mucosal barrier injury. In response to cytostatic drug treatment (arabinoside cytosine (Ara-C) and methotrexate (MTX)), NF-kappaB was activated in intestinal epithelial cells (IEC-6) resulting in an NF-kappaB-related induction of tumour necrosis factor alpha and monocyte chemoattractant protein-1. NF-kappaB inhibition increased the susceptibility of IEC-6 cells to Ara-C as well as MTX-induced cell death when obtained by the addition of caffeic acid phenethyl ester (CAPE), but not using curcumin. In an animal model for MTX-induced mucosal barrier injury, the induction of NF-kappaB-related cytokines and chemokines was detected upon treatment with MTX. Despite increased susceptibility shown in vitro, the inhibition of NF-kappaB resulted in a partial amelioration of villous atrophy normally seen in the small intestine upon MTX treatment. These results show that the inhibition of NF-kappaB does not increase intestinal side effects of the anticancer treatment, suggesting a safe use of curcumin and CAPE in combination with anticancer treatment.


Assuntos
Antineoplásicos/efeitos adversos , Curcumina/farmacologia , Mucosa Intestinal/efeitos dos fármacos , NF-kappa B/antagonistas & inibidores , Álcool Feniletílico/análogos & derivados , Animais , Ácidos Cafeicos/farmacologia , Linhagem Celular , Citarabina/farmacologia , Interações Medicamentosas , Feminino , Mucosa Intestinal/citologia , Mucosa Intestinal/patologia , Metotrexato/farmacologia , NF-kappa B/agonistas , Álcool Feniletílico/farmacologia , Ratos , Ratos Endogâmicos
9.
Br J Cancer ; 87(1): 113-8, 2002 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-12085266

RESUMO

During chemo- and radiation therapy, the balance between epithelial cell proliferation, differentiation, and cell death at the villus tip is disrupted by premature death of dividing epithelial cells. This will subsequently lead to the onset of mucosal barrier injury in the whole gastrointestinal tract. Up till now there is no validated method to treat side effects occurring due to therapy. An approach to manage this side effect might be to reversibly arrest growth of epithelial stem cells during therapy using Transforming Growth Factor-beta2. A Transforming Growth Factor-beta2 enriched fraction prepared from bovine milk was shown to protect small intestinal epithelial cells against cell cycle specific chemotherapeutic agents by arresting the cells in G1-phase. Secondly, in a rat model for induced small intestinal damage, oral supplementation of rats exposed to methotrexate with the Transforming Growth Factor-beta2 enriched fraction significantly reduced the chemotherapy-associated weight loss and ileal villus atrophy by reducing cell proliferation in the normal stem cell population. Thus oral supplementation with a bovine milk fraction enriched for Transforming Growth Factor-beta2 attenuated the side effects of chemotherapy in the small intestine in rats.


Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Ciclo Celular/efeitos dos fármacos , Imunossupressores/farmacologia , Intestino Delgado/patologia , Metotrexato/efeitos adversos , Fator de Crescimento Transformador beta/farmacologia , Administração Oral , Animais , Atrofia , Morte Celular , Modelos Animais de Doenças , Células Epiteliais/patologia , Feminino , Intestino Delgado/efeitos dos fármacos , Ratos , Fator de Crescimento Transformador beta2 , Redução de Peso
10.
J Biol Chem ; 274(31): 21847-52, 1999 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-10419502

RESUMO

We have measured the activation of the small GTPase Ral in human neutrophils after stimulation with fMet-Leu-Phe (fMLP), platelet activating factor (PAF), and granulocyte macrophage-colony stimulating factor and compared it with the activation of two other small GTPases, Ras and Rap1. We found that fMLP and PAF, but not granulocyte macrophage-colony stimulating factor, induce Ral activation. All three stimuli induce the activation of both Ras and Rap1. Utilizing specific inhibitors we demonstrate that fMLP-induced Ral activation is mediated by pertussis toxin-sensitive G-proteins and partially by Src-like kinases, whereas fMLP-induced Ras activation is independent of Src-like kinases. PAF-induced Ral activation is mediated by pertussis toxin-insensitive proteins, Src-like kinases and phosphatidylinositol 3-kinase. Phosphatidylinositol 3-kinase is not involved in PAF-induced Ras activation. The calcium ionophore ionomycin activates Ral, but calcium depletion partially inhibits fMLP- and PAF-induced Ral activation, whereas Ras activation was not affected. In addition, 12-O-tetradecanoylphorbol-13-acetate-induced activation of Ral is completely abolished by inhibitors of protein kinase C, whereas 12-O-tetradecanoylphorbol-13-acetate-induced Ras activation is largely insensitive. We conclude that in neutrophils Ral activation is mediated by multiple pathways, and that fMLP and PAF induce Ral activation differently.


Assuntos
Proteínas de Ligação ao GTP/sangue , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , N-Formilmetionina Leucil-Fenilalanina/farmacologia , Neutrófilos/fisiologia , Fator de Ativação de Plaquetas/farmacologia , Transdução de Sinais/fisiologia , Cálcio/sangue , Proteínas Quinases Dependentes de Cálcio-Calmodulina/sangue , Ativação Enzimática , GTP Fosfo-Hidrolases/sangue , Proteínas Ativadoras de GTPase , Humanos , Técnicas In Vitro , Cinética , Proteína Quinase 1 Ativada por Mitógeno , Neutrófilos/efeitos dos fármacos , Fosforilação , Proteína Quinase C/sangue , Proteínas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Acetato de Tetradecanoilforbol/farmacologia , Proteínas ral de Ligação ao GTP , Proteínas rap de Ligação ao GTP , Proteínas Ativadoras de ras GTPase
11.
Blood ; 92(6): 2133-40, 1998 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-9731072

RESUMO

The small GTPase Rap1 is highly expressed in human neutrophils, but its function is largely unknown. Using the Rap1-binding domain of RalGDS (RalGDS-RBD) as an activation-specific probe for Rap1, we have investigated the regulation of Rap1 activity in primary human neutrophils. We found that a variety of stimuli involved in neutrophil activation, including fMet-Leu-Phe (fMLP), platelet-activating factor (PAF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and IgG-coated particles, induce a rapid and transient Rap1 activation. In addition, we found that Rap1 is normally activated in neutrophils from chronic granulomatous disease patients that lack cytochrome b558 or p47phox and have a defective NADPH oxidase system. From these results we conclude that in neutrophils Rap1 is activated independently of respiratory burst induction. Finally, we found that Rap1 is activated by both the Ca2+ ionophore ionomycin and the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA), indicating that phospholipase C (PLC) activation leading to elevated levels of intracellular free Ca2+ and diacylglycerol (DAG) can mediate Rap1 activation. However, inhibition of PLC and Ca2+ depletion only marginally affected fMLP-induced Rap1 activation, suggesting that additional pathways may control Rap1 activation.


Assuntos
GTP Fosfo-Hidrolases/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Neutrófilos/enzimologia , Dinoprostona/farmacologia , Ativação Enzimática , Proteínas de Ligação ao GTP/efeitos dos fármacos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Humanos , N-Formilmetionina Leucil-Fenilalanina/farmacologia , Neutrófilos/efeitos dos fármacos , Fator de Ativação de Plaquetas/farmacologia , Fator ral de Troca do Nucleotídeo Guanina , Proteínas rap de Ligação ao GTP
12.
Biochem J ; 329 ( Pt 1): 121-30, 1998 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-9405284

RESUMO

Although it is known that many stimuli can activate mitogen-activated protein kinases (MAPKs) and phosphatidylinositol 3-kinases (PI3K) in human neutrophils, little is known concerning either the mechanisms or function of this activation. We have utilized a selective inhibitor of MAPK kinase (MEK), PD098059, and two inhibitors of PI3K, wortmannin and LY294002, to investigate the roles of these kinases in the regulation of neutrophil effector functions. Granulocyte/macrophage colony-stimulating factor, platelet-activating factor (PAF) and N-formylmethionyl-leucyl-phenylalanine are capable of activating both p44ERK1 and p42ERK2 MAPKs and phosphotyrosine-associated PI3K in human neutrophils. The activation of extracellular signal-related protein kinases (ERKs) is correlated with the activation of p21ras by both tyrosine kinase and G-protein-coupled receptors as measured by a novel assay for GTP loading. Wortmannin and LY294002 inhibit, to various degrees, superoxide generation, neutrophil migration and PAF release. Incubation with PD098059, however, inhibits only the PAF release stimulated by serum-treated zymosan. This demonstrates that, while neither MEK nor ERK kinases are involved in the activation of respiratory burst or neutrophil migration, inhibition of PAF release suggests a potential role in the activation of cytosolic phospholipase A2. PI3K isoforms, however, seem to have a much wider role in regulating neutrophil functioning.


Assuntos
Proteínas Quinases Ativadas por Mitógeno , Neutrófilos/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Quinases/metabolismo , Transdução de Sinais/fisiologia , Androstadienos/farmacologia , Western Blotting , Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Fatores Quimiotáticos/farmacologia , Quimiotaxia de Leucócito/efeitos dos fármacos , Cromonas/farmacologia , Citocinas/farmacologia , Flavonoides/farmacologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Humanos , Proteína Quinase 1 Ativada por Mitógeno , Proteína Quinase 3 Ativada por Mitógeno , Quinases de Proteína Quinase Ativadas por Mitógeno , Morfolinas/farmacologia , N-Formilmetionina Leucil-Fenilalanina/farmacologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/enzimologia , Proteína Oncogênica p21(ras)/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Fator de Ativação de Plaquetas/metabolismo , Fator de Ativação de Plaquetas/farmacologia , Inibidores de Proteínas Quinases , Explosão Respiratória/efeitos dos fármacos , Explosão Respiratória/fisiologia , Wortmanina , Zimosan/farmacologia
13.
FEBS Lett ; 410(1): 59-62, 1997 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-9247123

RESUMO

Rap1 (Krev-1) is a small GTPase first identified as a transformation suppressor of K-ras. This GTPase is very similar to Ras, particularly in the effector region, but its function is still elusive. Recent progress in the search for Rap1 function has come from the development of a novel assay to measure Rap1 activation. Using this assay activation of Rap1 was observed in human platelets and neutrophils after stimulation with various agonists. We speculate that Rap1 plays a role in one of the specialised functions of these cells.


Assuntos
GTP Fosfo-Hidrolases/fisiologia , Proteínas de Ligação ao GTP/fisiologia , Sequência de Aminoácidos , Animais , Plaquetas/enzimologia , Ativação Enzimática , GTP Fosfo-Hidrolases/genética , Proteínas de Ligação ao GTP/genética , Humanos , Dados de Sequência Molecular , Neutrófilos/enzimologia , Proteínas rap de Ligação ao GTP , Proteínas ras
14.
J Biol Chem ; 271(14): 7883-6, 1996 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-8626463

RESUMO

We report that expressing interfering mutants of the small Ras-related GTPase Rac, using either recombinant vaccinia virus or stable DNA transfection, eliminates epidermal growth factor-induced Ca2+ signaling, without affecting Ca2+ mobilization or influx from G protein-coupled receptors. Platelet-derived growth factor-dependent Ca2+ influx, however, is only partly sensitive to dominant negative Rac proteins. Thus, whereas epidermal growth factor-induced Ca2+ influx is completely mediated by Rac proteins, platelet-derived growth factor-induced Ca2+ influx involves Rac-dependent and -independent signaling pathways.


Assuntos
Cálcio/fisiologia , Receptores ErbB/fisiologia , Proteínas de Ligação ao GTP/fisiologia , Receptores do Fator de Crescimento Derivado de Plaquetas/fisiologia , Animais , Células Cultivadas , Fator de Crescimento Epidérmico/fisiologia , Células HeLa , Histamina/farmacologia , Humanos , Fator de Crescimento Derivado de Plaquetas/fisiologia , Ratos , Proteínas Recombinantes , Transdução de Sinais , Vaccinia virus , Proteínas rac de Ligação ao GTP , Proteínas rho de Ligação ao GTP
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