Mistletoe lectin dissociates into catalytic and binding subunits before translocation across the membrane to the cytoplasm

Агапов, И. И.; Tonevitsky, Alexander G.; Moysenovich, M M; Maluchenko, N. V.; Weyhenmeyer, Roland; Kirpichnikov, Mikhaǐl P.

doi:10.1016/s0014-5793(99)00639-0

Cited by 38 publications

(24 citation statements)

References 20 publications

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“…It has also been shown to increase reactivity of tumor-bearing mice lymphocytes to the mitogens ConA and LPS. Interestingly, in vitro, ML dissociates into catalytic subunits before translocating across the cell membrane and into the cytoplasm (Agapov et al, 1999).…”

Section: Mode Of Action Of Plant Lectinsmentioning

confidence: 99%

Lectins as Bioactive Plant Proteins: A Potential in Cancer Treatment

Mejı́a

Prisecaru

2005

Critical Reviews in Food Science and Nutrition

297

159

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Plant lectins, a unique group of proteins and glycoproteins with potent biological activity, occur in foods like wheat, corn, tomato, peanut, kidney bean, banana, pea, lentil, soybean, mushroom, rice, and potato. Thus, dietary intakes by humans can be significant. Many lectins resist digestion, survive gut passage, and bind to gastrointestinal cells and/or enter the circulation intact, maintaining full biological activity. Several lectins have been found to possess anticancer properties in vitro, in vivo, and in human case studies; they are used as therapeutic agents, preferentially binding to cancer cell membranes or their receptors, causing cytotoxicity, apoptosis, and inhibition of tumor growth. These compounds can become internalized into cells, causing cancer cell agglutination and/or aggregation. Ingestion of lectins also sequesters the available body pool of polyamines, thereby thwarting cancer cell growth. They also affect the immune system by altering the production of various interleukins, or by activating certain protein kinases. Lectins can bind to ribosomes and inhibit protein synthesis. They also modify the cell cycle by inducing non-apoptotic G1-phase accumulation mechanisms, G2/M phase cell cycle arrest and apoptosis, and can activate the caspase cascade. Lectins can also downregulate telomerase activity and inhibit angiogenesis. Although lectins seem to have great potential as anticancer agents, further research is still needed and should include a genomic and proteomic approach.

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Section: Mode Of Action Of Plant Lectinsmentioning

confidence: 99%

Lectins as Bioactive Plant Proteins: A Potential in Cancer Treatment

Mejı́a

Prisecaru

2005

Critical Reviews in Food Science and Nutrition

297

159

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“…The ML resistance of TA7 is far lower than that of hybridomas MNA8 and MNA9 producing monAbs against the native toxin: compared with control cells, they are 600 times less sensitive to ML [4]. Possibly, a transition state of the toxin with the TA7 epitope exposed is a short-lived one.…”

Section: Resultsmentioning

confidence: 92%

Mistletoe lectin A‐chain unfolds during the intracellular transport

et al. 1999

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Protein conformation during intracellular routing and translocation of the ribosome-inactivating proteins was investigated on hybridomas producing monoclonal antibodies (monAbs) against mistletoe lectin (ML). Decrease in the toxin activity towards these hybridomas is accounted for by the intracellular interaction of monAbs and the toxin resulting in the interruption of enzymatic subunit translocation into the cytosol. Obtained monAbs interacted with denatured ML A-chain (MLA) and a panel of MLA synthetic octapeptides linked to the surface of polyethylene pins. Enzyme-linked immunosorbent assay (ELI-SA) shows that monAbs recognize five epitopes in denatured MLA. Treatment of MLA by 3 M of guanidine hydrochloride leads to appearance of the epitopes. Hybridoma TA7 has been shown to be insensitive to cytotoxic action of ML. TA7 monAb as we have shown recognizes epitope 101^105, FTGTT, and inhibits the liposome aggregation induced by MLA. A study of the cytotoxicity of ML and ricin for the hybridomas revealed that the unfolding of A-chain is probably required for intracellular transport and cytotoxic activity of ML.z 1999 Federation of European Biochemical Societies.

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“…The toxin is translocated to the cytosol where it interacts with and inactivates ribosomes. Reduction of the disulphide bond and A-chain unfolding appears to be required before translocation to the cytosol (Agapov et al, 1999). The glycosylation of MLI, MLII and MLIII is different which may be a result of posttranslational processing or modifications that occur during processing of mistletoe preparations (Jäggy et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

Immunological Implications of the use of Plant Lectins for Drug and Vaccine Targeting to the Gastrointestinal Tract

Lavelle

Grant²,

Pfüller

et al. 2004

Journal of Drug Targeting

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Plant lectins are under consideration as targeting agents to enhance the efficacy of orally administered drugs and vaccines. A significant issue that must be considered is the immunogenicity of these molecules since an immune response to the targeting agent may interfere with its ability to interact with the epithelium. In contrast, the ability of certain lectins to activate the immune system may be exploited in the delivery of vaccines. We previously demonstrated that plant lectins vary widely in their immunogenicity and in particular that mistletoe lectins (ML) I, II and II (MLI, MLII, MLIII) are potent immunogens when administered nasotracheally. Here, we measured immune responses following oral delivery of the MLs and assessed their ability to enhance responses to a co-administered antigen to determine if the molecules possess adjuvant activity. Oral administration of the lectins induced potent lectin-specific systemic and mucosal antibody responses. In addition, each of the three lectins possessed adjuvant activity when delivered orally together with ovalbumin (OVA). The lectins enhanced both serum and mucosal antibody responses to the co-delivered antigen. This shows for the first time that MLI, MLII and MLIII possess adjuvant activity when administered orally and may provide a platform for the generation of effective mucosal adjuvants.

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Mistletoe lectin dissociates into catalytic and binding subunits before translocation across the membrane to the cytoplasm

Cited by 38 publications

References 20 publications

Lectins as Bioactive Plant Proteins: A Potential in Cancer Treatment

Lectins as Bioactive Plant Proteins: A Potential in Cancer Treatment

Mistletoe lectin A‐chain unfolds during the intracellular transport

Immunological Implications of the use of Plant Lectins for Drug and Vaccine Targeting to the Gastrointestinal Tract

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