Inhibition of protein synthesis by a toxic lectin from Viscum album L. (mistletoe).
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ABSTRACT:
SUBMITTER: Stirpe F
PROVIDER: S-EPMC1162167 | biostudies-other | 1980 Sep
REPOSITORIES: biostudies-other
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Project description:European mistletoe (Viscum album) is known for its special mode of cellular respiration. It lacks the mitochondrial NADH dehydrogenase complex (Complex I of the respiratory chain) and has restricted capacities to generate mitochondrial adenosine triphosphate (ATP). Here, we present an investigation of the V. album energy metabolism taking place in chloroplasts. Thylakoids were purified from young V. album leaves, and membrane-bound protein complexes were characterized by Blue native polyacrylamide gel electrophoresis as well as by the complexome profiling approach. Proteins were systematically identified by label-free quantitative shotgun proteomics. We identified >1,800 distinct proteins (accessible at https://complexomemap.de/va_leaves), including nearly 100 proteins forming part of the protein complexes involved in the light-dependent part of photosynthesis. The photosynthesis apparatus of V. album has distinct features: (1) comparatively low amounts of Photosystem I; (2) absence of the NDH complex (the chloroplast pendant of mitochondrial Complex I involved in cyclic electron transport (CET) around Photosystem I); (3) reduced levels of the proton gradient regulation 5 (PGR5) and proton gradient regulation 5-like 1 (PGRL1) proteins, which offer an alternative route for CET around Photosystem I; (4) comparable amounts of Photosystem II and the chloroplast ATP synthase complex to other seed plants. Our data suggest a restricted capacity for chloroplast ATP biosynthesis by the photophosphorylation process. This is in addition to the limited ATP supply by the mitochondria. We propose a view on mistletoe's mode of life, according to which its metabolism relies to a greater extent on energy-rich compounds provided by the host trees.
| S-EPMC9614478 | biostudies-literature
Project description:The high-resolution three-dimensional structure of the plant toxin viscotoxin A3, from Viscum album L., has been determined in solution by (1)H NMR spectroscopy at pH 3.6 and 12 degrees C (the structure has been deposited in the Protein Data Bank under the id. code 1ED0). Experimentally derived restraints including 734 interproton distances from nuclear Overhauser effect measurements, 22 hydrogen bonds, 32 φ angle restraints from J coupling measurements, together with three disulphide bridge constraints were used as input in restrained molecular dynamics, followed by minimization, using DYANA and Discover. Backbone and heavy atom root-mean-square deviations were 0.47+/-0.11 A (1 A=10(-10) m) and 0.85+/-0.13 A respectively. Viscotoxin A3 consists of two alpha-helices connected by a turn and a short stretch of antiparallel beta-sheet. This fold is similar to that found in other thionins, such as crambin, hordothionin-alpha and -beta, phoratoxin A and purothionin-alpha and -beta. The difference in the observed biological activity for thionins of known structure is discussed in terms of the differences in the calculated surface potential distribution, playing an important role in their function through disruption of cell membranes. In addition, the possible role in DNA binding of the helix-turn-helix motif of viscotoxin A3 is discussed.
| S-EPMC1221286 | biostudies-literature
Project description:In chemical pleurodesis for managing pulmonary air leak, tetracycline derivatives are commonly used, and their effectiveness has been established in many studies. Recently, a Viscum album extract was used in chemical pleurodesis. We compared the effects of V. album with those of a tetracycline derivative (doxycycline) to demonstrate the therapeutic effectiveness of the V. album extract in chemical pleurodesis for managing pulmonary air leak.Between October 2010 and October 2016, chemical pleurodesis was performed using doxycycline in 40 patients and the V. album extract in 37 patients. Thirty-three patients were in the postoperative state after pulmonary resection, and 44 patients suffered from spontaneous pneumothorax.No statistically significant difference in the success rate was observed between the 2 groups (V. album extract and doxycycline). In both groups, chest pain was the most common complication. More patients in the doxycycline group complained of severe chest pain (42.1% vs. 13.5%, p=0.006). In the V. album extract group, 24.3% of the patients required a chest tube to drain the pleural effusion after cessation of the air leak (doxycycline group: 5%, p=0.022). Further, the amount of pleural effusion drained on the day after the last chemical pleurodesis in the V. album extract group was greater than that in the doxycycline group (162.2±170.2 mL vs. 97.0±77.2 mL, p=0.032). All patients were discharged from the hospital without complications after pleural effusion drainage.Considering that treatment using the V. album extract was less painful, V. album might be a feasible option for chemical pleurodesis. However, pleural effusion should be monitored carefully when using V. album extract for treating patients suffering from air leak.
| S-EPMC5548205 | biostudies-other
Project description:MicroRNAs (miRNAs) are a class of approximately 22 nucleotides single-stranded non-coding RNA molecules that play crucial roles in gene expression. It has been reported that the plant miRNAs might enter mammalian bloodstream and have a functional role in human metabolism, indicating that miRNAs might be one of the hidden bioactive ingredients in medicinal plants. Viscum album L. (Loranthaceae, European mistletoe) has been widely used for the treatment of cancer and cardiovascular diseases, but its functional compounds have not been well characterized. We considered that miRNAs might be involved in the pharmacological activities of V. album. High-throughput Illumina sequencing was performed to identify the novel and conserved miRNAs of V. album. The putative human targets were predicted. In total, 699 conserved miRNAs and 1373 novel miRNAs have been identified from V. album. Based on the combined use of TargetScan, miRanda, PITA, and RNAhybrid methods, the intersection of 30697 potential human genes have been predicted as putative targets of 29 novel miRNAs, while 14559 putative targets were highly enriched in 33 KEGG pathways. Interestingly, these highly enriched KEGG pathways were associated with some human diseases, especially cancer, cardiovascular diseases and neurological disorders, which might explain the clinical use as well as folk medicine use of mistletoe. However, further experimental validation is necessary to confirm these human targets of mistletoe miRNAs. Additionally, target genes involved in bioactive components synthesis in V. album were predicted as well. A total of 68 miRNAs were predicted to be involved in terpenoid biosynthesis, while two miRNAs including val-miR152 and miR9738 were predicted to target viscotoxins and lectins, respectively, which increased the knowledge regarding miRNA-based regulation of terpenoid biosynthesis, lectin and viscotoxin expressions in V. album.
| S-EPMC5675405 | biostudies-literature
Project description:PacBio and Illumina Transcriptome Sequencing of Viscum album
| PRJEB60149 | ENA
Project description:Tumor cells have the capacity to secrete immunosuppressive substances in order to diminish dendritic cell (DC) activity and thereby escape from immune responses. The impact of mistletoe (Viscum album) extracts (VAE), which are frequently used as an additive anti-cancer therapy to stimulate the immune response, is still unknown. Using a human cellular system, the impact of two different VAE (VAEA + VAEI) on the maturation of human dendritic cells and on T cell function has been investigated using flow cytometry, automated fluorescence microscopy and cytokine bead array assays. Furthermore, we examined whether VAEI was able to counteract tumor-induced immunosuppression within this cellular system using a renal cancer cell model. The role of mistletoe lectin (ML) was analyzed using ML-specific antibodies and ML-depleted VAEI. VAEI and VAEA augmented the maturation of dendritic cells. VAEI abrogated tumor-induced immunosuppression of dendritic cells and both processes were partially mediated by ML since ML-depleted VAEI and ML-specific antibodies almost neutralized the rehabilitative effects of VAEI on DC maturation. Using these settings, co-culture experiments with purified CD4+ T cells had no influence on T cell proliferation and activation but did have an impact on IFN-? secretion. The study provides a potential mode-of-action of VAE as an additive cancer therapy based on immunomodulatory effects. However, the impact on the in vivo situation has to be evaluated in further studies.
| S-EPMC5515458 | biostudies-literature
Project description:Viscum album L. is a semiparasitic plant grown on trees and widely used for the treatment of many diseases in traditional and complementary therapy. It is well known that some activities of Viscum album extracts are varied depending on the host trees, such as antioxidant, apoptosis-inducing, anticancer activities of the plant. The aim of the present study is to examine the comparative effects of methanolic extracts of V. album grown on three different host trees (locust tree, lime tree, and hedge maple tree) on H(2)O(2)-induced DNA damage in HeLa cells. Oxidative damage in mitochondrial DNA and two nuclear regions was assessed by QPCR assay. The cells were pretreated with methanolic extracts (10 μg/mL) for 48 h, followed by the treatment with 750 μM H(2)O(2) for 1 hour. DNA damage was significantly induced by H(2)O(2) while it was inhibited by V. album extracts. All extracts completely protected against nuclear DNA damage. While the extract from lime tree or white locust tree entirely inhibited mitochondrial DNA damage, that from hedge maple tree inhibited by only 50%. These results suggest that methanolic extracts of V. album can prevent oxidative DNA damage, and the activity is dependent on the host tree.
| S-EPMC3440025 | biostudies-literature