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1.
Toxins (Basel) ; 12(9)2020 08 22.
Article in English | MEDLINE | ID: mdl-32842591

ABSTRACT

The safety of concentrated food complements intake is a major health concern. It has been well established that green tea polyphenols (GTPs) consumption promotes healthy effects. However, the ingestion of large amounts of GTPs is a matter of controversy due to reported adverse effects. We underwent a preliminary exploration of the effects of the oral administration of a standardized concentrated GTPs preparation on mice which suffered from reversible intestinal derangement promoted by sublethal amounts of the antiribosomal lectin ebulin f from dwarf elder (Sambucus ebulus L.). Neither independent oral administration of 30 mg/kg body weight Polyphenon 60 nor intraperitoneal administration of 2.5 mg/kg body weight ebulin f triggered lethal toxicity. In contrast, the simultaneous administration of these same doses of both Polyphenon 60 and ebulin f triggered an important and unexpected synergistic toxic action featured by the biphasic reduction of weight, which continued after eight days, reaching a reduction of 40%. Lethality appeared 2 days after the onset of the combined treatment and reached more than 50% after 10 days.


Subject(s)
Intestines/drug effects , Polyphenols/isolation & purification , Polyphenols/toxicity , Sambucus/toxicity , Tea/toxicity , Animals , Female , Intestines/pathology , Mice , Plant Extracts/isolation & purification , Plant Extracts/toxicity
2.
Curr Pharm Des ; 26(16): 1778-1789, 2020.
Article in English | MEDLINE | ID: mdl-32048961

ABSTRACT

Lactose is a reducing sugar consisting of galactose and glucose, linked by a ß (1→4) glycosidic bond, considered as an antioxidant due to its α-hydroxycarbonyl group. Lactose is widely ingested through the milk and other unfermented dairy products and is considered to be one of the primary foods. On the other hand, lactose is also considered as one of the most widely used excipients for the development of pharmaceutical formulations. In this sense, lactose has been related to numerous drug-excipient or drug-food pharmacokinetic interactions. Intolerance, maldigestion and malabsorption of carbohydrates are common disorders in clinical practice, with lactose-intolerance being the most frequently diagnosed, afflicting 10% of the world's population. Four clinical subtypes of lactose intolerance may be distinguished, namely lactase deficiency in premature infants, congenital lactase deficiency, adult-type hypolactasia and secondary lactase intolerance. An overview of the main uses of lactose in human nutrition and in the pharmaceutical industry and the problems derived from this circumstance are described in this review.


Subject(s)
Lactose Intolerance , Lactose , Adult , Animals , Eating , Humans , Infant , Lactase/chemistry , Lactase/metabolism , Milk/metabolism
3.
Toxins (Basel) ; 10(8)2018 08 16.
Article in English | MEDLINE | ID: mdl-30115887

ABSTRACT

A pyrogen is a substance that causes fever after intravenous administration or inhalation. Gram negative endotoxins are the most important pyrogens to pharmaceutical laboratories. In the International, United States, Japanese and European Pharmacopoeias, there are two official methods to evaluate pyrogenicitythat is, the bacterial endotoxin test, and the pyrogen test. The main objective of this review is to compare the monographs of each test among the different Pharmacopeias, to detect similarities and differences. The former can be considered fully harmonized, and only non-significant differences were detected. The latter, which is the only available assay for some products and formulations to demonstrate apyrogenicity, shows large differences, which should be considered.


Subject(s)
Biological Assay , Endotoxins , Pharmacopoeias as Topic , Pyrogens , Animals , Humans
4.
Histol Histopathol ; 33(9): 979-986, 2018 Sep.
Article in English | MEDLINE | ID: mdl-29683470

ABSTRACT

Ebulin f is a ribosome-inactivating protein (RIP) present in green fruits of the dwarf elder (Sambucus ebulus L). Since dwarf elder fruits are used for food and as a medicine, we assessed the study of toxicological effects and safety of ebulin f in elderly mice, comparing these results with those reported in young animals and with other RIPs. Female Swiss mice aged 6 and 12 months of age were intraperitoneally injected with a single dose from 1.4 to 4.5 mg/kg ebulin f. Heart, stomach, intestines, lung, kidney, liver, spleen, pancreas, adrenal gland, uterus, ovary and brain were studied. Histology analysis was carried out by staining with hematoxylin and eosin and Masson's trichrome observed with a light microscope, or apoptosis detection by TUNEL method observed with a confocal laser microscope. Treated animals injected with the lower dose could recover their weights, but after 14 days half of them died. The higher dose caused a progressive loss of body weight leading to death. In the animals of the experimental groups it was found atrophy of Lieberkühn's crypts, pneumonia, nephronal degeneration, myocardial atrophy, centrolobular hepatic necrosis, splenic white pulp necrosis foci and increased rate of apoptosis in the intestines and liver, in which apoptoses were mainly located in the vicinity of the lobular central vein. We conclude that ebulin f affects vital organs in elderly mice.


Subject(s)
Plant Extracts/toxicity , Ribosome Inactivating Proteins, Type 2/toxicity , Animals , Body Weight , Female , Intestines/drug effects , Mice , Sambucus/chemistry
5.
Molecules ; 22(1)2017 Jan 06.
Article in English | MEDLINE | ID: mdl-28067841

ABSTRACT

Elderberry contains healthy low molecular weight nutraceuticals and lectins which are sequence-related to the elderberry allergen Sam n1. Some of these lectins are type II ribosome-inactivating proteins. The sensitivity of native lectins present in elderberry fruits and bark to the proteolysis triggered by in vitro simulated gastric and duodenal fluids has been investigated. It was found that these lectins are refractory to proteolysis. Nonetheless, incubation for 5-10 min in a boiling water bath completely sensitized them to the hydrolytic enzymes in vitro. Under these conditions neither total Folin-Ciocalteau's reagent reactive compounds, total anthocyanins and the mixture of cyanidin-3-glucoside plus cyanidin-3-sambubioside, nor antioxidant and free-radical scavenging activities were affected by more than 10% for incubations of up to 20 min. Therefore, short-time heat treatment reduces potential allergy-related risks deriving from elderberry consumption without seriously affecting its properties as an antioxidant and free-radical scavenging food.


Subject(s)
Allergens/chemistry , Antioxidants/chemistry , Fruit/chemistry , Plant Lectins/chemistry , Ribosome Inactivating Proteins, Type 2/chemistry , Sambucus nigra/chemistry , Allergens/isolation & purification , Antioxidants/isolation & purification , Hot Temperature , Pepsin A/chemistry , Plant Bark/chemistry , Plant Extracts/chemistry , Plant Lectins/isolation & purification , Plants, Medicinal , Protein Stability , Proteolysis , Ribosome Inactivating Proteins, Type 2/isolation & purification , Spain
6.
Food Chem ; 220: 324-330, 2017 Apr 01.
Article in English | MEDLINE | ID: mdl-27855907

ABSTRACT

Ebulin f and SELfd are two lectins of Sambucus ebulus L. that show different stability and digestibility properties in gastric fluid due to their structural differences which may explain their different toxicological profiles. The main aim was to determine the effects of pH, temperature and sugar binding on the intrinsic structures of both proteins by fluorescence analyses. Quenching experiments were conducted, under different pH and temperature conditions, with acrylamide (uncharged) and iodide (charged), to study the possible changes of their intrinsic fluorescence. Results revealed that the native structure of SELfd is more folded than that of ebulin f. At pH 2.0, ebulin f displayed a more open structure than at neutral pH. It can be concluded that this is the main reason why ebulin f is accessible to pepsin action and more sensitive to degradation, in contrast to SELfd as we reported previously.


Subject(s)
Lectins/chemistry , Ribosome Inactivating Proteins, Type 2/chemistry , Sambucus/chemistry , Hydrogen-Ion Concentration , Pepsin A/metabolism , Protein Conformation , Temperature
7.
Toxins (Basel) ; 8(6)2016 06 10.
Article in English | MEDLINE | ID: mdl-27294959

ABSTRACT

Endoglin (CD105) is an accessory component of the TGF-ß receptor complex, which is expressed in a number of tissues and over-expressed in the endothelial cells of tumor neovasculature. Targeting endoglin with immunotoxins containing type 2 ribosome-inactivating proteins has proved an effective tool to reduce blood supply to B16 mice tumor xenografts. We prepared anti-endoglin immunotoxin (IT)-containing recombinant musarmin 1 (single chain ribosome-inactivating proteins) linked to the mouse anti-human CD105 44G4 mouse monoclonal antibody via N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP). The immunotoxin specifically killed L929 fibroblast mouse cells transfected with the short form of human endoglin with IC50 values in the range of 5 × 10(-10) to 10(-9) M.


Subject(s)
Endoglin/immunology , Immunotoxins/pharmacology , N-Glycosyl Hydrolases/pharmacology , Animals , Cell Line , Cell Survival/drug effects , Humans , Mice
8.
Toxins (Basel) ; 7(2): 367-79, 2015 Feb 02.
Article in English | MEDLINE | ID: mdl-25648843

ABSTRACT

All parts of dwarf elder (Sambucus ebulus L.) studied so far contain a ribosome-inactivating protein with lectin activity (ribosome-inactivating lectin; RIL), known as ebulin. Green fruits contain ebulin f, the toxicity of which has been studied in six-week-old mice, where it was found that the intestines were primary targets for it when administered intraperitoneally (i.p.). We performed experiments to assess whether ebulin f administration to six- and 12-month-old mice would trigger higher toxicity than that displayed in six-week-old mice. In the present report, we present evidence indicating that the toxicological effects of ebulin f after its i.p. administration to elderly mice are exerted on the lungs and intestines by an increased rate of apoptosis. We hypothesize that the ebulin f apoptosis-promoting action together with the age-dependent high rate of apoptosis result in an increase in the lectin's toxicity, leading to a higher lethality level.


Subject(s)
Aging , Intestines/drug effects , Lung/drug effects , Ribosome Inactivating Proteins, Type 2/toxicity , Aging/drug effects , Aging/pathology , Animals , Dose-Response Relationship, Drug , Female , Fruit/chemistry , Injections, Intraperitoneal , Intestines/pathology , Kaplan-Meier Estimate , Lung/pathology , Mice , Ribosome Inactivating Proteins, Type 2/isolation & purification , Sambucus/chemistry
9.
Molecules ; 20(2): 2364-87, 2015 Jan 30.
Article in English | MEDLINE | ID: mdl-25647575

ABSTRACT

Sambucus (Adoxaceae) species have been used for both food and medicine purposes. Among these, Sambucus nigra L. (black elder), Sambucus ebulus L. (dwarf elder), and Sambucus sieboldiana L. are the most relevant species studied. Their use has been somewhat restricted due to the presence of bioactive proteins or/and low molecular weight compounds whose ingestion could trigger deleterious effects. Over the last few years, the chemical and pharmacological characteristics of Sambucus species have been investigated. Among the proteins present in Sambucus species both type 1, and type 2 ribosome-inactivating proteins (RIPs), and hololectins have been reported. The biological role played by these proteins remains unknown, although they are conjectured to be involved in defending plants against insect predators and viruses. These proteins might have an important impact on the nutritional characteristics and food safety of elderberries. Type 2 RIPs are able to interact with gut cells of insects and mammals triggering a number of specific and mostly unknown cell signals in the gut mucosa that could significantly affect animal physiology. In this paper, we describe all known RIPs that have been isolated to date from Sambucus species, and comment on their antiviral and entomotoxic effects, as well as their potential uses.


Subject(s)
Fruit/chemistry , Plant Extracts/pharmacology , Ribosome Inactivating Proteins/pharmacology , Sambucus/chemistry , Animals , Humans , Molecular Targeted Therapy , Plant Extracts/isolation & purification , Ribosome Inactivating Proteins/isolation & purification , Ribosome Inactivating Proteins/physiology
10.
Toxins (Basel) ; 7(3): 648-58, 2015 Feb 25.
Article in English | MEDLINE | ID: mdl-25723322

ABSTRACT

Sambucus ebulus L. (dwarf elder) is a medicinal plant, the usefulness of which also as food is restricted due to its toxicity. In the last few years, both the chemistry and pharmacology of Sambucus ebulus L. have been investigated. Among the structural and functional proteins present in the plant, sugar-binding proteins (lectins) with or without anti-ribosomal activity and single chain ribosome-inactivating proteins (RIPs) have been isolated. RIPs are enzymes (E.C. 3.2.2.22) that display N-glycosidase activity on the 28S rRNA subunit, leading to the inhibition of protein synthesis by arresting the step of polypeptide chain elongation. The biological role of all these proteins is as yet unknown. The evidence suggests that they could be involved in the defense of the plant against predators and viruses or/and a nitrogen store, with an impact on the nutritional characteristics and food safety. In this mini-review we describe all the isoforms of ebulin that have to date been isolated from dwarf elder, as well as their functional characteristics and potential uses, whilst highlighting concern regarding ebulin toxicity.


Subject(s)
Ribosome Inactivating Proteins, Type 2/chemistry , Sambucus/chemistry , Cloning, Molecular , Lectins/chemistry , Lectins/isolation & purification , Plants, Medicinal/chemistry , Protein Biosynthesis , RNA, Ribosomal, 28S/genetics , Ribosome Inactivating Proteins, Type 2/isolation & purification
11.
Plant Foods Hum Nutr ; 69(2): 168-74, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24793353

ABSTRACT

Dwarf elder (Sambucus ebulus L.) berries are rich in health-promoting phytochemicals such as polyphenols and anthocyanins, and display a significant antioxidant activity. They are also rich in two lectins (ebulin f and SELfd) that share amino acid sequence homology with the elderberry allergen Sam n1 present in Sambucus nigra pollen and fruits. Ebulin f displays toxicity by oral ingestion. This study was aimed at eliminating the toxicity of these lectins whilst having little or no effect on the antioxidant properties of dwarf elder berries. We thus investigated the potential effects of incubation in a boiling water bath of extracts from several parts of the plant on total polyphenol content, antioxidant activity, total anthocyanins, cyanidin-3-glycoside content, and the sensitivity of purified dwarf elder fruit lectins to a simulated gastric fluid. The study shows that five minutes of said heat treatment fully sensitized both lectins to pepsin digestion, whilst minimally reducing phenol and antioxidant as well as free radical scavenging activities to below 13%. It proved possible to eliminate the potential risks derived from the presence of lectins in dwarf elder juices without any significant reduction in the content of the antioxidant compounds. Dwarf elder berries may thus be a valuable nutritional source.


Subject(s)
Anthocyanins/analysis , Food Technology/methods , Plant Lectins/analysis , Polyphenols/analysis , Sambucus/chemistry , Antioxidants/analysis , Antioxidants/pharmacology , Fruit/chemistry , Fruit/growth & development , Glycosides/analysis , Heating , Pepsin A/chemistry , Plant Lectins/chemistry , Plant Lectins/toxicity , Plants, Medicinal/chemistry , Ribosome Inactivating Proteins, Type 2/chemistry
12.
Histol Histopathol ; 29(8): 1057-63, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24563426

ABSTRACT

Ribosome-inactivating lectins (RILs) are A-B type toxins like ricin whose molecular target is the large rRNA of eukaryotic ribosome. Administration of lethal doses of the RIL nigrin b isolated from elderberry (Sambucus nigra L.) bark triggers specific intestinal derangement. The aim of the present research was to explore the early effects of a lethal dose of nigrin b (16 mg/kg body weight) on the small intestine using light and electron microscopy to ascertain intestinal epithelium changes. 6 h after nigrin administration, the small intestine crypts began to show signs of damage with cells appearing at different stages of apoptosis. 16 h after injection crypts appeared more impaired, including the derangement of Paneth cells. The novelty of our results is that the Paneth cells in the small intestine in addition to stem cells are the early cellular targets for nigrin b.


Subject(s)
Paneth Cells/drug effects , Plant Proteins/toxicity , Ribosome Inactivating Proteins/toxicity , Animals , Apoptosis/drug effects , Female , Intestine, Small/drug effects , Intestine, Small/pathology , Mice , Paneth Cells/pathology
13.
Toxins (Basel) ; 5(10): 1767-79, 2013 Oct 14.
Article in English | MEDLINE | ID: mdl-24129061

ABSTRACT

Sambucus species contain a number of lectins with and without antiribosomal activity. Here, we show that dwarf elder (Sambucus ebulus L.) blossoms express two D-galactose-binding lectins that were isolated and purified by affinity chromatography and gel filtration. These proteins, which we named ebulin blo (A-B toxin) and SELblo (B-B lectin)--blo from blossoms--were subjected to molecular characterization and analysis by MALDI-TOF mass spectrometry and tryptic peptide fingerprinting. Both lectins share a high degree of amino acid sequence homology with Sambucus lectins related to the Sam n1 allergen. Ebulin blo, but not SELblo, was highly toxic by nasal instillation to mice. Overall, our results suggested that both lectins would belong to an allergen family exemplified by Sam n1 and could trigger allergy responses. Furthermore, they raise a concern about ebulin blo toxicity.


Subject(s)
Allergens/isolation & purification , Flowers/chemistry , Plant Lectins/isolation & purification , Plant Proteins/isolation & purification , Sambucus , Allergens/chemistry , Allergens/toxicity , Amino Acid Sequence , Animals , Female , Mice , Molecular Sequence Data , Plant Lectins/chemistry , Plant Lectins/toxicity , Plant Proteins/chemistry , Plant Proteins/toxicity
14.
Food Chem ; 136(2): 794-802, 2013 Jan 15.
Article in English | MEDLINE | ID: mdl-23122129

ABSTRACT

Some lectins from Sambucus spp. share amino acid sequences with the pollen Sam n1 allergen. The lectins ebulin f and SELfd from the early stages of growth were isolated and subjected to analysis by MALDI-TOF mass spectrometry, tryptic peptide fingerprinting, molecular characterization and pepsin digestibility. The molecular mass (33.214) and other structural features of the Sam n1 allergen fit best with a monomeric lectin like SELlm (Mr 34.2 kDa) found in shoots of dwarf elder. Ebulin f toxicity to mice was higher intraperitoneally than orally at the same dose (5mg/kg body weight). In contrast SELfd at the same dose lacks of apparent toxicity. Ebulin f, but not SELfd, undergoes extensive pepsin proteolysis, which could explain the differences in toxicity. The present study supports our hypothesis that the Sam n1 allergen could be a sequence-related monomeric lectin like SELlm present in shoots of Sambucus ebulus rather than ebulin.


Subject(s)
Galectins/pharmacology , Gastric Juice/metabolism , Plant Proteins/pharmacology , Sambucus/chemistry , Animals , Female , Fruit/chemistry , Galectins/chemistry , Galectins/isolation & purification , Humans , Mice , Molecular Weight , Plant Proteins/chemistry , Plant Proteins/isolation & purification , Up-Regulation/drug effects
15.
Cancer Immunol Immunother ; 62(3): 541-51, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23076642

ABSTRACT

TGF-beta superfamily co-receptors are emerging as targets for cancer therapy, acting both directly on cells and indirectly on the tumour neovasculature. Endoglin (CD105), an accessory component of the TGF-beta receptor complex, is expressed in certain melanoma cell lines and the endothelial cells of tumour neovessels. Targeting endoglin with immunotoxins is an attractive approach for actively suppressing the blood supply to tumours. Here, we report evidence indicating that endoglin is expressed in mouse melanoma B16MEL4A5 and mouse fibroblast L929 cell lines. We prepared an immunotoxin to target endoglin by coupling the rat anti-mouse MJ7/18 (IgG2a) monoclonal antibody (mAb) to the non-toxic type 2 ribosome-inactivating protein nigrin b (Ngb) with N-succinimidyl 3-(2-pyridyldithio)-propionate (SPDP) as a linker with a molar nigrin b at a MJ7/18 stoichiometry of 2:1. The MJ7-Ngb immunotoxin generated killed both cell lines, with IC50 values of 4.2 × 10(-9) M for B16MEL4A5 and 7.7 × 10(-11) M for L929 cells. For in vivo assays of the immunotoxin, B16MEL4A5 cells were injected subcutaneously into the right flanks of 6-week-old C57BL/6 J mice. When the animals developed palpable solid tumours, they were subjected to treatment with the immunotoxin. While treatment with either MJ7/18 mAb or Ngb did not affect tumour development, treatment with the immunotoxin completely and steadily blocked tumour growth up to 7 days, after which some tumours re-grew. Thus, vascular-targeting therapy with this anti-vascular immunotoxin could promote the destruction of newly created tumour vessels at early stages of B16MEL4A5 tumour development and readily accessible CD105+ B16MEL4A5 melanoma cells.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antigens, CD/immunology , Immunotoxins/therapeutic use , Melanoma, Experimental/therapy , Plant Proteins/administration & dosage , Receptors, Cell Surface/immunology , Ribosome Inactivating Proteins/administration & dosage , Animals , Antibodies, Monoclonal/pharmacology , Cell Line , Cell Line, Tumor , Endoglin , Immunotoxins/pharmacology , Melanoma, Experimental/blood supply , Mice , Mice, Inbred C57BL , Neovascularization, Pathologic/drug therapy
16.
Toxicon ; 61: 26-9, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23142777

ABSTRACT

Dwarf elder fruits (Sambucus ebulus) contain the ribosome-inactivating lectin ebulin f structurally related to ricin. We investigated intraperitoneal toxicity of ebulin f in mice and found that it triggers specific derangement of the intestines. Ebulin f was much less toxic than ricin to mice when administered intraperitoneally. The targets were cells of the intestinal crypts, which underwent apoptosis. Small intestine crypts were more sensitive than large intestine crypts.


Subject(s)
Lectins/chemistry , Lectins/toxicity , Ribosome Inactivating Proteins, Type 2/chemistry , Ribosome Inactivating Proteins, Type 2/toxicity , Sambucus/chemistry , Animals , Apoptosis/drug effects , Body Weight/drug effects , Fruit , Injections, Intraperitoneal , Intestine, Small/pathology , Kaplan-Meier Estimate , Mice , Ricin/toxicity , Survival Analysis
17.
Med Chem ; 8(6): 996-1002, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22779758

ABSTRACT

Endoglin (CD105), a cell-surface co-receptor for transforming growth factor-beta (TGF-ß) superfamily members, is over-expressed in tumor neovasculature and can be targeted with anti-endoglin antibodies, thus becoming an important tool for anti-tumoral therapy. Injury of the mouse tail induced the transient expression of endoglin, this peaking at three days after injury and disappearing six days later. An immunotoxin containing the anti-mouse endoglin rat monoclonal antibody MJ7/18 and the non-toxic ribosome-inactivating protein nigrin b (Ngb) was found to be very active in targeting mouse endoglin in the L929 fibroblast cell line (IC(50) of 4 x 10(-11) M). At that concentration, the immunotoxin lacked unspecific activity. Upon induction of endoglin after injury, the MJ7-Ngb immunotoxin strongly attacked and deranged the injured tail, inducing tissue damage. Such effects were dependent on the age of the animals and were evident in six-week-old mice, but not in eight-month-old mice. Our results indicate that endoglin is up-regulated in newly formed vessels upon injury and can be targeted by the MJ7-Ngb immunotoxin; thus, it could be a useful tool for tumor ablation research.


Subject(s)
Immunotoxins/toxicity , Intracellular Signaling Peptides and Proteins/immunology , Intracellular Signaling Peptides and Proteins/metabolism , Plant Proteins/immunology , Ribosome Inactivating Proteins/immunology , Tail/blood supply , Tail/injuries , Up-Regulation/drug effects , Veins/drug effects , Animals , Antibodies, Monoclonal/immunology , Antibody Specificity , Cell Line , Endoglin , Humans , Immunomodulation/drug effects , Immunotoxins/immunology , Male , Mice , Rabbits , Time Factors
18.
Toxins (Basel) ; 3(5): 420-41, 2011 05.
Article in English | MEDLINE | ID: mdl-22069717

ABSTRACT

The type 2 ribosome-inactivating proteins (RIPs) isolated from some species belonging to the Sambucus genus, have the characteristic that although being even more active than ricin inhibiting protein synthesis in cell-free extracts, they lack the high toxicity of ricin and related type 2 RIPs to intact cells and animals. This is due to the fact that after internalization, they follow a different intracellular pathway that does not allow them to reach the cytosolic ribosomes. The lack of toxicity of type 2 RIPs from Sambucus make them good candidates as toxic moieties in the construction of immunotoxins and conjugates directed against specific targets. Up to now they have been conjugated with either transferrin or anti-CD105 to target either transferrin receptor- or endoglin-overexpressing cells, respectively.


Subject(s)
Antineoplastic Agents/pharmacology , Immunotoxins/pharmacology , Neoplasms/drug therapy , Ribosome Inactivating Proteins, Type 2/chemistry , Ribosome Inactivating Proteins, Type 2/pharmacology , Sambucus/chemistry , Animals , Antibodies, Monoclonal/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/therapeutic use , Cell Survival/drug effects , HeLa Cells , Humans , Immunotoxins/chemistry , Immunotoxins/therapeutic use , Lethal Dose 50 , Models, Molecular , Neoplasms/immunology , Protein Conformation , Ribosome Inactivating Proteins, Type 2/genetics , Ribosome Inactivating Proteins, Type 2/isolation & purification
19.
Biochimie ; 92(1): 71-80, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19799962

ABSTRACT

Sialic acid-binding dwarf elder agglutinin (SEA) present only in rhizomes of the medicinal plant Sambucus ebulus L., was found to be a tetrameric glycoprotein consisting of two covalently-associated dimers of an enzymic A chain with rRNA N-glycosidase activity (EC 3.2.2.22) linked to a B chain with agglutinin properties. The lectin inhibited protein synthesis by a cell-free system and depurinated ribosomes. Cloning of the corresponding gene and molecular modeling of the deduced amino acid sequence demonstrated that SEA has a three-dimensional structure which resembles that reported for other two tetrameric type 2 RIPs from Sambucus (SNAI and SSA). The lectin agglutinated red blood cells and displayed sugar affinity for sialic acid residues apart from d-galactose, binding to the mucin-producing gut goblet cells. Since sialic acid is present in animal cells, especially in epithelial lining gut cells, but not in plants, SEA could play a role in the defense against insect attack. The nucleotide sequence reported in this paper has been submitted to the GenBank nucleotide database under accession number AM981401.


Subject(s)
Glycoside Hydrolases/metabolism , N-Acetylneuraminic Acid/metabolism , Nucleic Acids/metabolism , Plant Lectins/chemistry , Plant Lectins/metabolism , Sambucus , Amino Acid Sequence , Animals , COS Cells , Chemical Phenomena , Chlorocebus aethiops , Cloning, Molecular , Hemagglutination/drug effects , Models, Molecular , Molecular Sequence Data , Phylogeny , Plant Lectins/genetics , Plant Lectins/pharmacology , Protein Structure, Quaternary , Rhizome , Ribosome Inactivating Proteins, Type 2/chemistry , Ribosome Inactivating Proteins, Type 2/metabolism
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