1º - OS HUMANOS APENAS MUITO RECENTEMENTE DO PONTO DE VISTA DO TEMPO BIOLÓGICO COMEÇARAM A CONSUMIR CEREAIS;
2º - NA VERDADE, GENETICAMENTE O HOMEM NÃO É UM GRANÍVORO;
3º - OS CEREAIS CONTÊM ANTI-NUTRIENTES E LECTINAS QUE PODEM DANIFICAR O SEU INTESTINO (MESMO DEPOIS DE COZINHADOS);
4º - A GENERALIDADE DOS CEREAIS SÃO NÃO BIOLÓGICOS E ESTÃO CHEIOS DE HERBICIDAS, FUNGICIDAS E INSECTICIDAS;
5º - A OPÇÃO PELOS CEREAIS INTEGRAIS PODE SER UMA PIOR ESCOLHA, PORQUANTO É NA PARTE MAIS RICA EM FIBRA QUE SE CONCENTRAM A MAIOR PARTE DOS ANTI-NUTRIENTES E TAMBÉM DOS TÓXICOS;
6º - EXISTE JÁ UM VASTO CONJUNTO DE INVESTIGAÇÃO QUE CORROBORA A TESE DE QUE OS CEREAIS (TAL COMO AS LEGUMINOSAS) PODEM AUMENTAR A PERMEABILIDADE INTESTINAL E PROVOCAR SÍNDROME DO INTESTINO PERMEÁVEL E OS SINTOMAS A ELE ASSOCIADOS (CÓLON IRITÁVEL, COLITE, DOENÇA CELÍACA, CROHN, COLITE ULCEROSA);
7º - A PARTE DA POPULAÇÃO QUE TOLERA OS CEREAIS (E AS LEGUMINOSAS) DEVE SER CONSIDERADA MINORITÁRIA E NÃO MAIORITÁRIA;
OS CEREAIS CONTÊM ANTI-NUTRIENTES QUE PODEM DANIFICAR A SUA SAÚDE
O Dr. Loren Cordain, professor na Colorado State University sublinha:
"There's no human requirement for grains. That's the problem with the USDA recommendations. They think we're hardwired as a species to eat grains. You can get by just fine and meet every single nutrient requirement that humans have without eating grains. And grains are absolutely poor sources of vitamins and minerals compared to fruits and vegetables and meat and fish."
"Grains are the seeds of a plant. They're its reproductive material, and plants don't make their reproductive material to give away for free to other animals. If they did they'd become extinct, and so the evolutionary strategy that many plants, particularly cereal grains have taken to prevent predation is to evolve toxic compounds so that the predator of the seeds can't eat them, so that they can put their seeds in the soil where they're meant to be to grow a new plant and not in the gut of an animal to feed it."
OS CEREAIS, ESPECIALMENTE OS INTEGRAIS, AUMENTAM A PERMEABILIDADE INTESTINAL
A síndrome do intestino permeável pode provocar sintomas como gazes e dores abdominais, mas pode estar na origem de outros quadros patológicos como fadiga, problemas de pele, dores articulares, alergias, autismo, alterações psicológicas, etc. Para esta permeabilidade intestinal concorre não só o glúten e a gliadina, mas de forma particularmente intensa os tóxicos com que os cereais são "fustigados" (Glifosato(Roundup) e muitos outros), .
OS CEREAIS, ESPECIALMENTE OS INTEGRAIS NÃO BIOLÓGICOS, PRODUZEM INFLAMAÇÃO SISTÉMICA E AUMENTAM A POSSIBILIDADE DE VIR A PADECER DE DOENÇAS DEGENERATIVAS/AUTOIMUNES
Tanto a matriz de ADN da proteína contida no trigo, centeio, cevada e aveia, como a lectina neles presente, bem assim como a carga de pesticidas, herbicidas e fungicidas que eles transportam, são um dos factores determinantes para o desenvolvimento de patologias como OBESIDADE, DIABETES, TRANSTORNOS GASTRO-INTESTINAIS, PATOLOGIA CARDÍACA, DEPRESSÃO, ALZHEIMER, ESCLEROSE MÚLTIPLA E OUTRAS PATOLOGIAS AUTOIMUNES.
OS CEREAIS, SÃO AINDA ALTAMENTO PROMOTORES DA ELEVAÇÃO DO AÇÚCAR NO SANGUE (GLICOSE) E DA PROMOÇÃO DA RESISTÊNCIA À INSULINA
Com efeito, a lectina neles presente tem a faculdade de imitar a insulina no organismo, o que aliado ao elevado indíce insulinogénico dos mesmos, leva a que grande parte da população comece desde muito cedo, desde criança, a criar resistência à insulina, DESENVOLVENDO A DENOMINADA SÍNDROME METABÓLICA, que está na origem do desenvolvimento das doenças metabólicas como a diabetes e a obesidade.
As lectinas são mecanismos-chave para as plantas se protegerem de serem comidas e encontram-se em maior concentração nas suas sementes por serem estas que visam a propagação da espécie.
Quando os animais consomem alimentos ricos em lectinas podem sentir desconforte abdominal e toda uma outra série de queixas. Apenas uma longa coexistência com determinada fonte alimentar pode permitir a adaptação do organismo a essa fito-toxina. Como os humanos apenas consomem grãos à cerca de 10.000 anos, eles são mais atreitos a sofrer efeitos adversos que outros animais como as aves e roedores que as consomem à centenas de milhares ou milhões de anos.
A gliadina (gluten) é a proteína imunotóxica primária presente em cereais como o trigo, centeio, cevada e aveia e é uma das substâncias mais prejudiciais à nossa saúde aumentando a permeabilidade intestinal e podendo coduzir à doença celíaca. A WGA (Wheat Germ Agglutinin) é uma das mais problemáticas uma vez que não é eliminada na germinação e encontra-se mais concentrada nos cereais integrais.
No caso da WGA a investigação aponta para ela ser causa provável de uma série de problemas de saúde:
Pro-inflammatória—a WGA estimula a síntese de mensageiros químicos pro-inflamatórios (citoquinas) nas células intestinais e imunitárias e demonstrou ser uma das causas da inflamação crónica do intestino delgado .Immunotoxicidade—a WGA induz atrofia do timo em ratos e, nos humanos, demonstrou-se que leva à produção de anti-corpos na corrente sanguínea que reagem com outras proteínas levando a fenómenos de auto-imunidade. Neurotoxicidade—a WGA pode passer a barreira hemato-encefálica através de um processo denominado “endocitose adsortiva”.A WGA pode agredir a faixa de mielina dos nervos e é capaz de inibir o factor de crescimento dos nervos , indispensável ao crescimento, manutenção e sobrevivência de certos neurónios- alvo. Excitotoxicidade—o trigo, mas também os lacticíneos e a soja, contêm elevados níveis de ácido aspártico e glutâmico que fazem deles potencialmente excitotóxicos. A excitotoxicidade é um processo patológico em que os ácidos aspártico e glutâmico causam um sobre-reacção dos receptores nervosos celulares que pode conduzir à calcificação nervosa e a dano cerebral. Estes dois aminoácidos podem contribuir para doenças neurodegenerativas como o Alzheimer, a esclerose múltipla, a Doença de Huttington, epilepsia, ADD/ADHD e enxaquecas.
Citotoxicidade—a WGA demonstrou ser citotóxica quer para as células, podendo levar a apoptose celular . Interrompe a função endócrina—a WGA pode contribuir para o aumento de peso, resistência à insulina e resistência à leptina, por bloqueio do receptor de lepina no hipotálamo. Ela liga-se, também, tanto aos nódoles benignos como malignos da tiróide e interfere com a produção de secretina o que pode conduzir a problemas digestivos e hipertrofia pancreática.
Cardiotoxicidade—a WGA tem um potente efeito disruptivo nos trombócitos celulares endoteliais , que desempenham um papel chave na regeneração tecidular e na remoção segura de neutrófilos dos vasos sanguíneos. Afecta negativamente a função absortiva – por efeito eliminador das vilosidades intestinais e irritação e permeabilização da parede do intetino
Uma ideia pré-concebida do passado era a de que os cereais integrais eram mais saudáveis que os refinados. Na verdade, não são porquanto a concentração de lectinas (WGA) é maior e a de agrotóxicos também. E não se pense que a germinação, a fermentação ou a cozedura conseguem eliminar esses anti-nutrientes e muito menos o agrotóxicos. Na verdade as lectinas estão preparadas para sobreviver a uma variedade de ph e temperaturas e a WGA é particularmente resistente uma vez que é formada pelas mesmas ligações dissulfídicas que dão força e resistência ao cabelo humano e à borracha galvanizada e os agrotóxicos são ultraresistentes ao calor.
De novo Loren Cordain:
"The nutritional qualities of modern processed foods and foods introduced during the Neolithic period are discordant with our ancient and conservative genome. This genetic discordance ultimately manifests itself as various chronic illnesses, which have been dubbed "diseases of civilization." By severely reducing or eliminating these foods and replacing them with a more healthful cuisine, possessing nutrient qualities more in line with the foods our ancestors consumed, it is possible to improve health and reduce the risk of chronic disease."
Effects of wheat germ agglutinin on human gastrointestinal epithelium: insights from an experimental model of immune/epithelial cell interaction.
Dalla Pellegrina C, Perbellini O, Scupoli MT, Tomelleri C, Zanetti C, Zoccatelli G, Fusi M, Peruffo A, Rizzi C, Chignola R.
Department of Biotechnology, University of Verona, Strada Le Grazie 15-CV1, I-37134 Verona, Italy.
Wheat germ agglutinin (WGA) is a plant protein that binds specifically to sugars expressed, among many others, by human gastrointestinal epithelial and immune cells. WGA is a toxic compound and an anti-nutritional factor, but recent works have shown that it may have potential as an anti-tumor drug and as a carrier for oral drugs. To quantitate the toxicity threshold for WGA on normal epithelial cells we previously investigated the effects of the lectin on differentiated Caco2 cells, and showed that in the micromolar range of concentrations WGA could alter the integrity of the epithelium layer and increase its permeability to both mannitol and dextran. WGA was shown to be uptaken by Caco2 cells and only approximately 0.1% molecules were observed to cross the epithelium layer by transcytosis. Here we show that at nanomolar concentrations WGA is unexpectedly bioactive on immune cells. The supernatants of WGA-stimulated peripheral blood mononuclear cells (PBMC) can alter the integrity of the epithelium layer when administered to the basolateral side of differentiated Caco2 cells and the effects can be partially inhibited by monoclonal antibodies against IL1, IL6 and IL8. At nanomolar concentrations WGA stimulates the synthesis of pro-inflammatory cytokines and thus the biological activity of WGA should be reconsidered by taking into account the effects of WGA on the immune system at the gastrointestinal interface. These results shed new light onto the molecular mechanisms underlying the onset of gastrointestinal disorders observed in vivo upon dietary intake of wheat-based foods.
PMID: 19332085 [PubMed - indexed for MEDLINE]
Lectin glycosylation as a marker of thin gut inflammation
Gloria V. Guzyeyeva
Medicine, Saratov Medical State University, Saratov, Russian Federation
Mucous maturation in human gastrointestinal system remains unexplored. It has been previously reported that changes in lectin receptors glycosylation might serve as histochemistry markers of thing gut inflammation. The aim of this study was to compare the binding pattern of biotinylated lectins in different subtypes of thin gut inflammation in the early childhood The study was performed on biopsy material of 120 patients with chronic thin gut inflammation and 30 healthy controls with different lectins: Peanut agglutinin (PNA), Soybean agglutinin (SBA), Wheat germ agglutinin (WGA), Lens culinaris (LcL), Laburnum anagyroides (LAL). Presence of N- and O-glycans in the composition of proteins of plasmatic membranes of a thin gut was shown. Sialic acids were absent in the composition of alkaline phosphatase of mature mucous production. The expression of lectin-binding glycoconjugates exhibited differences between certain types of chronic thin gut inflammation. WGA with affinity for GlcNAc and neuraminic acid labelled the cells with early thin gut inflammation but most intensely those of fibroblastic type. Staining with PNA and SBA, which are GalNAc specific, were strongly positive. Enhanced PNA reactivity reflected mainly cytoarchitectural pattern. These results documented the heterogeneous glycosylation pattern in different subtypes of thin gut inflammation and indicate the usefulness of lectins in the early evaluation of pluripotential differentiation of thin gut secretory cells.[Sponsored by NIH grants from Russian Federation].
Antinutritive effects of wheat-germ agglutinin and other N-acetylglucosamine-specific lectins.
Pusztai A, Ewen SW, Grant G, Brown DS, Stewart JC, Peumans WJ, Van Damme EJ, Bardocz S.
Br J Nutr. 1993 Jul;70(1):313-21. Rowett Research Institute, Bucksburn, Aberdeen.
Incorporation of N-acetylglucosamine-specific agglutinins from wheat germ (Triticum aestivum; WGA), thorn apple (Datura stramonium) or nettle (Urtica dioica) rhizomes in the diet at the level of 7 g/kg reduced the apparent digestibility and utilization of dietary proteins and the growth of rats, with WGA being the most damaging. As a result of their binding and endocytosis by the epithelial cells of the small intestine, all three lectins were growth factors for the gut and interfered with its metabolism and function to varying degrees. WGA was particularly effective; it induced extensive polyamine-dependent hyperplastic and hypertrophic growth of the small bowel by increasing its content of proteins, RNA and DNA. Furthermore, an appreciable portion of the endocytosed WGA was transported across the gut wall into the systemic circulation, where it was deposited in the walls of the blood and lymphatic vessels. WGA also induced the hypertrophic growth of the pancreas and caused thymus atrophy. Although the transfer of the gene of WGA into crop plants has been advocated to increase their insect resistance, as the presence of this lectin in the diet may harm higher animals at the concentrations required to be effective against most pests, its use in plants as natural insecticide is not without health risks for man.
PMID:8399111 [PubMed - indexed for MEDLINE]
Natural human antibodies to dietary lectins.
Tchernychev B, Wilchek M.
FEBS Lett. 1996 Nov 18;397(2-3):139-42. Department of Membrane Research and Biophysics, The Weizmann Institute of Science, Rehovot, Israel.
Natural antibodies to self and non-self proteins, including dietary proteins, are a significant part of the immune repertoire of humans. Antibodies to three structurally related legume lectins (Erythrina corallodendron lectin (ECorL), peanut agglutinin (PNA), and soybean agglutinin (SBA)) and to one cereal lectin (wheat germ agglutinin (WGA)) were purified by affinity chromatography from human sera and their binding specificity examined. The anti-SBA, anti-ECorL and anti-WGA antibodies exhibited high specificity, whereas the anti-PNA antibodies were polyreactive. Although the anti-WGA antibodies were highly specific for WGA, they also crossreacted slightly toward some other proteins. The anti-ECorL antibodies bound to native SBA, but the anti-SBA antibodies failed to bind to the native ECorL. Although the anti-SBA and anti-ECorL antibodies both exhibited specificity when interacting with native lectins, they bound to a wider range of denatured lectins, indicating a common or universal epitope which is recognized by many natural antibodies. Interestingly, the natural antibodies did not interfere with the agglutination properties of the lectins. These findings may provide a basis for studying the in vivo biological effects of anti-dietary protein antibodies, including those against carbohydrate-binding proteins.
PMID:8955334 [PubMed - indexed for MEDLINE]
Transcytotic pathway for blood-borne protein through the blood-brain barrier.
Broadwell RD, Balin BJ, Salcman M.
Division of Neuropathology, University of Maryland School of Medicine, Baltimore 21201.
The transcytosis of blood-borne protein through the blood-brain barrier, a consequence of recruitment of the Golgi complex within nonfenestrated cerebral endothelia, was identified in mice and rats injected intravenously with the lectin wheat germ agglutinin (WGA) conjugated to the enzymatic tracer horseradish peroxidase (HRP). WGA enters cells by adsorptive endocytosis after binding to specific cell surface oligosaccharides. Blood-borne WGA-HRP labeled the entire cerebrovascular tree from the luminal side 5 min after injection; pericytes, located on the abluminal surface of cerebral endothelia, sequestered the lectin conjugate 6 hr later. Endothelial organelles harboring WGA-HRP 3 hr after injection included the luminal plasmalemma, endocytic vesicles, endosomes (prelysosomes), secondary lysosomes, and the Golgi complex. The peroxidase reaction product labeled the abluminal surface of cerebral endothelia and occupied the perivascular clefts by 6 hr. Within 12 hr, organelles labeled with WGA-HRP in pericytes were identical to those observed in endothelia. Blood-borne native HRP, entering cells by bulk-phase endocytosis, was neither directed to the Golgi complex nor transferred across nonfenestrated cerebral endothelia. The results suggest that blood-borne molecules taken into the cerebral endothelium by adsorptive endocytosis and conveyed to the Golgi complex can, either by themselves or as vehicles for other molecules excluded from the brain, undergo transcytosis through the blood-brain barrier without compromising the integrity of the barrier.
PMID:2448779 [PubMed - indexed for MEDLINE] PMCID:PMC279605
Distribution of concanavalin A and wheat germ agglutinin binding sites in the rat peripheral nerve fibres revealed by lectin/glycoprotein-gold histochemistry.
Department of Anatomy and Histology, Medical University, Sofia, Bulgaria.
The affinity of rat peripheral nerve fibres for concanavalin A (Con A) and wheat germ agglutinin (WGA) was tested in semi-thin sections of Epon-embedded material. A two-step post-embedding technique was used. As a first step, Con A and WGA were used in pure form. As a second step, peroxidase-gold (for Con A) and ovomucoid-gold (for WGA) complexes were applied. The lectin-binding sites, visualized by means of signal amplification with the photochemical silver reaction, were associated mainly with the myelin sheaths and the surfaces of Schwann cells.
PMID:8866643 [PubMed - indexed for MEDLINE]
Wheat germ agglutinin, concanavalin A, and lens culinalis agglutinin block the inhibitory effect of nerve growth factor on cell-free phosphorylation of Nsp100 in PC12h cells.
Hashimoto S, Hagino A.
Department of Biochemistry, Tohoku Dental University, Koriyama, Japan.
It has been shown that in PC12 and its subclone PC12h treatment of the cells with nerve growth factor (NGF) induces a selective decrease in the incorporation of radioactive phosphate into a 100,000-dalton protein, designated in an earlier study as Nsp100, in the subsequent phosphorylation of soluble extracts from cells with (gamma-32P)ATP. In the present study, we show that plant lectins, wheat germ agglutinin (WGA), concanavalin A (Con A), and lens culinaris agglutinin (LCA), inhibit the action of NGF on Nsp100 phosphorylation in PC12h cells. Treatment of the cells with WGA, which binds to N-acetylglucosamine and sialic acid residues on glycoproteins, strongly blocked the inhibitory action of NGF on the protein phosphorylation. Con A and LCA, both of which recognize the same specific sugars (mannose, glucose), displayed only a moderate blocking effect. Unlike the native lectin, succinylated WGA, which has the ability to bind to N-acetylglucosamine but not to sialic acid residues, and other lectins examined in this study did not inhibit the action of NGF on Nsp100. WGA-mediated inhibition of NGF action was reversed by the addition of N-acetylglucosamine and by the addition of a much lower concentration of a sialoglycoprotein, mucin, into the culture. Since the binding of succinylated WGA to N-acetylglucosamine residues of cell-surface glycoconjugates is not sufficient to prevent the action of NGF, WGA might act on sialic acid residues of the NGF receptor molecule to effect the inhibition of biological actions of NGF.
PMID:2720800 [PubMed - indexed for MEDLINE]
Wheat germ lectin induces G2/M arrest in mouse L929 fibroblasts.
Liu WK, Sze SC, Ho JC, Liu BP, Yu MC.
Department of Anatomy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong. email@example.com
Wheat germ lectin (WGA) is a cytotoxic lectin for many cell lines [Wang et al., 2000], but its underlying mechanism is not clear. In this report, we found that incubation of synchronized mouse L929 fibroblasts with WGA resulted in a dose-dependent reduction of intracellular incorporation of 3H-thymidine and MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide)-conversion activity (IC50 congruent with 0.4 microM). Fluorescein-conjugated WGA was demonstrated to transport from the cell surface into the paranuclear region of cultured L929 cells within 30 min, and subsequently evoked lipid peroxidation of plasma membrane and vacuolation in the cytoplasm of these cells. Studies with tritiated thymidine incorporation, immunofluorescence microscopy, immunoblotting analysis and flow cytometry revealed that WGA inhibited cell cycle progression after one replication, resulting in G2/M arrest and alteration of cell cycle regulatory proteins, particularly activation of p21Cip1/WAF1 and suppression of cyclin B and cdc 2. Although there was an increase of cytosolic caspase 3 and bax protein expression, no apoptotic bodies were observed by both fluorescence and transmission electron microscopy. These results suggest that WGA arrested L929 proliferation after one cell cycle in the G2/M phase through activation of the p21Cip1/WAF1 and suppression of Cyclin B-Cdc2.
Copyright 2004 Wiley-Liss, Inc.PMID:15048871 [PubMed - indexed for MEDLINE]
Analysis of lectin binding in benign and malignant thyroid nodules.
Sasano H, Rojas M, Silverberg SG.
Arch Pathol Lab Med. 1989 Feb;113(2):186-9. Department of Pathology, George Washington University Medical Center, Washington, DC 20037.
The lectin binding properties of ten cases each of adenomatoid nodule, follicular adenoma, and papillary carcinoma and five cases of microinvasive follicular carcinoma were examined histochemically and compared with adjacent normal thyroid tissue. Wheat germ agglutinin, concanavalin A, Ulex europaeus agglutinin I, peanut agglutinin, soybean agglutinin, Dolichos biflorus agglutinin, Ricinus communis agglutinin, and Helix pomatia agglutinin were employed. All the lectins but Ulex europaeus agglutinin I, peanut agglutinin, and Helix pomatia agglutinin were bound to thyroid parenchymal cells, colloid and stromal cells, but none uniquely to thyroid parenchymal cells. Helix pomatia agglutinin binding was present in stromal cells but not in parenchymal cells. Ulex europaeus agglutinin I binding to parenchymal cells was weakly positive only in five cases of papillary carcinoma. The binding in adenomatoid and neoplastic cells and their colloid was stronger than in adjacent normal thyroid tissue in all cases examined. Wheat germ agglutinin and concanavalin A binding was most intense among the lectins examined. In papillary carcinoma, lectin binding was observed mostly in the apical cytoplasm of carcinoma cells, whereas a diffuse surface binding pattern was predominant in follicular adenoma and carcinoma, adenomatoid nodules and normal thyroid gland. No consistent differences in lectin binding were found between follicular adenoma and carcinoma, or between adenomatoid nodules and follicular neoplasia.
PMID:2916907 [PubMed - indexed for MEDLINE]
Wheat germ agglutinin-induced platelet activation via platelet endothelial cell adhesion molecule-1: involvement of rapid phospholipase C gamma 2 activation by Src family kinases.
Ohmori T, Yatomi Y, Wu Y, Osada M, Satoh K, Ozaki Y.
Department of Laboratory Medicine, Yamanashi Medical University, Nakakoma, Yamanashi 409-3898, Japan.
Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) is a 130K transmembrane glycoprotein that belongs to the immunoglobulin gene superfamily and is expressed on the surface of hematological or vascular cells, including platelets and endothelial cells. Although the importance of this adhesion molecule in various cell-cell interactions is established, its function in platelets remains ill-defined. In the process of clarifying the mechanism by which the lectin wheat germ agglutinin (WGA) activates platelets, we unexpectedly discovered that PECAM-1 is involved in signal transduction pathways elicited by this N-acetyl-D-glucosamine (NAGlu)-reactive lectin. WGA, which is a very potent platelet stimulator, elicited a rapid surge in Syk and phospholipase C (PLC)-gamma 2 tyrosine phosphorylation and the resultant intracellular Ca(2+) mobilization; collagen, as reported, induced these responses, but in a much slower and weaker manner. WGA strongly induced tyrosine phosphorylation of a 130-140K protein, which was confirmed to be PECAM-1 by immunoprecipitation and immunodepletion studies. WGA-induced PECAM-1 tyrosine phosphorylation occurred rapidly, strongly and in a manner independent of platelet aggregation or cell-cell contact; these characteristics of PECAM-1 phosphorylation were not mimicked at all by receptor-mediated platelet agonists. In addition, WGA was found to associate with PECAM-1 itself, and anti-PECAM-1 antibody, as well as NAGlu, specifically inhibited WGA-induced platelet aggregation. In PECAM-1 immunoprecipitates, Src family tyrosine kinases existed, and a kinase activity was detected, which increased upon WGA stimulation. Furthermore, the Src family kinase inhibitor PP2 inhibited WGA-induced platelet aggregation, Ca(2+) mobilization, and PLC-gamma 2 tyrosine phosphorylation. Finally, WGA induced PECAM-1 tyrosine phosphorylation and cytoskeletal reorganization in vascular endothelial cells. Our results suggest that (i) PECAM-1 is involved in WGA-induced platelet activation, (ii) PECAM-1 clustering by WGA activates unique and strong platelet signaling pathways, leading to a rapid PLC activation via Src family kinases, and (iii) WGA is a useful tool for elucidating PECAM-1-mediated signaling with wide implications not confined to platelets.
PMID:11669637 [PubMed - indexed for MEDLINE]
Decreased levels of heat shock proteins in gut epithelial cells after exposure to plant lectins.
Ovelgönne JH, Koninkx JF, Pusztai A, Bardocz S, Kok W, Ewen SW, Hendriks HG, van Dijk JE.
Gut. 2000 May;46(5):679-87. Department of Veterinary Pathology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, PO Box 80.158, 3508 TD Utrecht, Netherlands.
The enterocytes of the intestinal epithelium are regularly exposed to potentially harmful substances of dietary origin, such as lectins. Expression of heat shock proteins (HSPs) by this epithelium may be part of a protective mechanism developed by intestinal epithelial cells to deal with noxious components in the intestinal lumen.
To investigate if the lectins PHA, a lectin from kidney beans (Phaseolus vulgaris) and WGA, a lectin from wheat germ (Triticum aestivum) could modify the heat shock response in gut epithelial cells and to establish the extent of this effect.
Jejunal tissue sections from PHA and WGA fed rats were screened for expression of HSP70, HSP72, and HSP90 using monoclonal antibodies. Differentiated Caco-2 cells, the in vitro counterpart of villus enterocytes, were exposed to 100 microg/ml of PHA-E(4) or WGA for 48 hours and investigated for changes in DNA and protein synthesis by double labelling with [2-(14)C]thymidine and L-[methyl-(3)H]methionine. The relative concentrations of HSP60, HSP70, HSP72, and HSP90 and binding protein (BiP) in these cells exposed to lectins were analysed by polyacrylamide gel electrophoresis and immunoblotting. To establish if lectin exposed differentiated Caco-2 cells were still capable of producing a heat shock response, these cells received a heat shock (40 degrees C, 41 degrees C, and 42 degrees C) for one hour and were allowed to recover for six hours at 37 degrees C. During heat shock and recovery periods, lectin exposure was continued.
Constitutive levels of HSPs were measured in the intestinal cells of lactalbumin fed (control) rats, as may be expected from the function of this tissue. However, in PHA and WGA fed rats a marked decline in the binding of antibodies against several HSPs to the intestinal epithelium was found. These results were confirmed by in vitro experiments using differentiated Caco-2 cells exposed to PHA-E(4) and WGA. However, after exposure to lectins, these cells were still capable of heat induced heat shock protein synthesis, and total protein synthesis was not impaired indicating specific inhibition of HSP synthesis in non-stressed cells.
We conclude that PHA and WGA decrease levels of stress proteins in rat gut and enterocyte-like Caco-2 cells, leaving these cells less well protected against the potentially harmful content of the gut lumen.
PMID:10764712 [PubMed - indexed for MEDLINE]