maitotoxin and Glioma

maitotoxin has been researched along with Glioma* in 7 studies

Other Studies

7 other study(ies) available for maitotoxin and Glioma

ArticleYear
Syntheses and Biological Activities of the LMNO, ent-LMNO, and NOPQR(S) Ring Systems of Maitotoxin.
    The Journal of organic chemistry, 2017, 09-15, Volume: 82, Issue:18

    Structure-activity relationship studies of maitotoxin (MTX), a marine natural product produced by an epiphytic dinoflagellate, were conducted using chemically synthesized model compounds corresponding to the partial structures of MTX. Both enantiomers of the LMNO ring system were synthesized via aldol reaction of the LM ring aldehyde and the NO ring ketone. These fragments were derived from a common cis-fused pyranopyran intermediate prepared through a sequence involving Nozaki-Hiyama-Kishi reaction, intramolecular oxa-Michael addition, and Pummerer rearrangement. The NOPQR(S) ring system, in which the original seven-membered S ring was substituted with a six-membered ring, was also synthesized through the coupling of the QR(S) ring alkyne and the NO ring aldehyde and the construction of the P ring via 1,4-reduction, dehydration, and hydroboration. The inhibitory activities of the synthetic specimens against MTX-induced Ca

    Topics: Aldehydes; Animals; Calcium; Dose-Response Relationship, Drug; Glioma; Ketones; Marine Toxins; Molecular Conformation; Nitric Oxide; Oxocins; Pyrans; Rats; Stereoisomerism

2017
Artificial ladder-shaped polyethers that inhibit maitotoxin-induced Ca2+ influx in rat glioma C6 cells.
    Bioorganic & medicinal chemistry letters, 2012, Jun-01, Volume: 22, Issue:11

    Maitotoxin (MTX) is a ladder-shaped polyether produced by the epiphytic dinoflagellate Gambierdiscus toxicus. It is known to elicit potent toxicity against mammals and induce influx of Ca(2+) into cells. An artificial ladder-shaped polyether possessing a 6/7/6/6/7/6/6 heptacyclic ring system, which was designed for elucidating interactions with transmembrane proteins, was found to be the most potent inhibitor against MTX-induced Ca(2+) influx that has ever been reported.

    Topics: Animals; Calcium; Dinoflagellida; Ethers, Cyclic; Glioma; Hydrophobic and Hydrophilic Interactions; Ion Transport; Marine Toxins; Membrane Proteins; Oxocins; Rats; Tumor Cells, Cultured

2012
Maitotoxin-induced nerve growth factor production accompanied by the activation of a voltage-insensitive Ca2+ channel in C6-BU-1 glioma cells.
    British journal of pharmacology, 1999, Volume: 127, Issue:7

    1. The aim of the present study was to determine the effects of maitotoxin on nerve growth factor production and the Ca2+ influx in clonal rat glioma cells (C6-BU-1). 2. Maitotoxin (1 - 10 ng ml-1) induced a profound increase in 45Ca2+ influx in an extracellular Ca2+-dependent manner. However, high KCl had no effect at all. These effects were supported by the results from the analysis of intracellular Ca2+ concentration using fura 2. 3. The maitotoxin-induced 45Ca2+ influx was inhibited by inorganic Ca2+ antagonists, such as Mg2+, Mn2+ and Co2+. The inhibitory effect of Co2+ was antagonized by increasing the extracellular Ca2+ concentrations. 4. Maitotoxin (3 ng ml-1) as well as A-23187 (1microM) and dibutyryl cyclic AMP (0.5 mM) caused an acceleration of nerve growth factor (NGF) production in C6-BU-1 cells, as determined by NGF enzyme immunoassay. 5. Reverse transcription polymerase chain reaction (RT - PCR) analysis showed that maitotoxin (10 ng ml-1) enhanced the expression of NGF mRNA, which was abolished by the removal of extracellular Ca2+. A-23187 also accelerated its expression. 6. These results suggest that maitotoxin activates a voltage-insensitive Ca2+ channel and accelerates NGF production mediated through a Ca2+ signalling pathway in C6-BU-1 glioma cells.

    Topics: Animals; Brain Neoplasms; Bucladesine; Calcimycin; Calcium Channel Agonists; Calcium Channels; Cell Line; Fluorescent Dyes; Fura-2; Glioma; Immunoenzyme Techniques; Marine Toxins; Neoplasm Proteins; Nerve Growth Factors; Oxocins; Rats; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Stimulation, Chemical; Tumor Cells, Cultured

1999
Maitotoxin-induced calcium influx in erythrocyte ghosts and rat glioma C6 cells, and blockade by gangliosides and other membrane lipids.
    Chemical research in toxicology, 1999, Volume: 12, Issue:10

    Maitotoxin (MTX) at 0.3 nM elicited a 10-20-fold increase in the level of Ca(2+) influx in rat glioma C6 cells. At higher doses (3-30 nM), MTX induced marked Ca(2+) influx in human erythrocyte ghosts when monitored with the fluorescent dye Fura-2. Although the ghosts were not as susceptible to MTX as intact erythrocytes or other cell lines, Fura-2 experiments under various conditions suggested that the MTX-induced entry of ions into the ghosts was mediated by a mechanism similar to that reported for cells or tissues. These ghosts are the simplest system known to be sensitive to MTX and thus may be suitable for research on the direct action of MTX. Gangliosides GM1 and GM3, glycosphingolipids which have a sialic acid residue, strongly inhibited MTX-induced Ca(2+) influx in C6 cells, while the inhibitory action by asialo-GM1, which lacks a sialic acid residue, was somewhat weaker. Their inhibitory potencies were in the following order: GM1 (IC(50) approximately 2 microM) > GM3 (IC(50) approximately 5 microM) > asialo-GM1 (IC(50) approximately 20 microM). GM1 (3 microM) completely blocked MTX (30 nM)-induced Ca(2+) influx in human erythrocyte ghosts. When C6 cells were pretreated with tunicamycin, an antibiotic which inhibits N-linked glycosylation, or concanavalin A, a lectin which exhibits a high affinity for cell-surface oligosaccharides, MTX-induced Ca(2+) influx was significantly potentiated. This suggests that removal of oligosaccharides from the cell surface by tunicamycin or capping of sugar chains on plasma membranes by concanavalin A can potentiate the action of MTX.

    Topics: Animals; Anti-Bacterial Agents; Brain Neoplasms; Calcium; Calcium Radioisotopes; Concanavalin A; Erythrocyte Membrane; Fluorescent Dyes; Fura-2; Gangliosides; Glioma; Marine Toxins; Membrane Lipids; Membrane Potentials; Models, Molecular; Molecular Conformation; Oxocins; Rats; Tumor Cells, Cultured; Tunicamycin

1999
Inhibition of maitotoxin-induced Ca2+ influx in rat glioma C6 cells by brevetoxins and synthetic fragments of maitotoxin.
    Journal of neurochemistry, 1998, Volume: 70, Issue:1

    45Ca2+ influx in rat glioma C6 cells induced by 0.3 nM maitotoxin (MTX) was markedly inhibited by brevetoxin A (PbTx1) and brevetoxin B (PbTx2), with EC50 values of 16 and 13 microM, respectively. This inhibition was observed immediately after addition of MTX when monitored with fura-2, which suggests that PbTx2 directly blocks the action of MTX. This blockade by PbTx2 was not affected by tetrodotoxin, which excludes the involvement of voltage-sensitive sodium channels. The depolarizing effects of these brevetoxins were also not a likely cause of this inhibition, because melittin, a channel-forming peptide, did not significantly block MTX-induced 45Ca2+ influx. Instead, this inhibition was thought to be mediated by blockade of an MTX-binding site by the brevetoxins, based on the fact that these toxins, particularly PbTx2, closely mimic the partial structure of MTX. Synthetic fragments of MTX corresponding to the hydrophilic EF-GH rings (200 microM) and LM-NO rings (500 microM) of MTX significantly reduced MTX-elicited Ca2+ influx. The observation that the effects of MTX were inhibited by structural mimics of both its hydrophobic and hydrophilic portions implies that both portions of the MTX molecule recognize its target.

    Topics: Animals; Calcium; Calcium Channel Blockers; Electrophysiology; Fluorescent Dyes; Fura-2; Glioma; Marine Toxins; Molecular Conformation; Oxocins; Peptide Fragments; Rats; Tumor Cells, Cultured

1998
Maitotoxin effects are blocked by SK&F 96365, an inhibitor of receptor-mediated calcium entry.
    Molecular pharmacology, 1992, Volume: 41, Issue:3

    The dinoflagellate toxin maitotoxin (MTX) elicited a sustained increase of [Ca2+]i in C6 glioma cells. This response was inhibited by SK&F 96365, a blocker of receptor-mediated calcium entry. In C6 cells, endothelin-1 elicited a rapid but transient increase in [Ca2+]i, followed by a smaller sustained increase. SK&F 96365 inhibited the sustained increase in [Ca2+]i. In both C6 glioma cells and RIN insulinoma cells, MTX elicited a marked influx of 45Ca2+. SK&F 96365 inhibited MTX-induced 45Ca2+ influx by 95% at 30 microM. The L-type calcium channel blocker nifedipine, even at 10 microM, inhibited MTX-induced calcium uptake by only 20% in RIN cells and by only 10% in C6 cells. MTX elicited calcium-dependent phosphoinositide breakdown in both C6 and RIN cells. In both cell lines, the MTX-induced phosphoinositide breakdown was inhibited by 90% by SK&F 96365 at 30 microM. Endothelin-1 and carbamylcholine elicited phosphoinositide breakdown in C6 cells and RIN cells, respectively. The stimulations were unaffected by the presence of SK&F 96365 up to 100 microM. In RIN insulinoma cells, MTX elicited calcium-dependent release of insulin. SK&F 96365 at 30 microM inhibited MTX-induced insulin release by 75%, whereas nifedipine, even at 30 microM, inhibited release by only 10%. The blockade of MTX-induced responses by SK&F 96365 indicates that MTX increases intracellular calcium by interacting directly with a calcium-entry system that is similar, in its sensitivity to SK&F 96365, to the calcium-entry system activated by receptors that elicit phosphoinositide breakdown. Activation of phospholipase C and hormone release by MTX also are blocked by SK&F 96365 and, thus, may be secondary to the activation of such a calcium-entry system.

    Topics: Calcium; Calcium Channel Blockers; Carbachol; Endothelins; Glioma; Imidazoles; Insulin; Marine Toxins; Nifedipine; Oxocins; Phosphatidylinositols; Radioimmunoassay; Tumor Cells, Cultured

1992
Partial structures and binding studies of maitotoxin, the most potent marine toxin.
    Bulletin de la Societe de pathologie exotique (1990), 1992, Volume: 85, Issue:5 Pt 2

    Partial structures of maitotoxin (MTX) were deduced by extensive two-dimensional NMR measurements, showing that the toxin had carbon-carbon double bonds in both termini of the molecule, and a primary alcohol group at the end. These functionalities were used for preparation of a radioligand of MTX; [3H]H-MTX and [3H]benzoyl-MTX. Both radioligands had high levels of non-specific binding to tissues. The binding of [3H]MTX to rat glioma C6 cells was inhibited by a didesulfo-MTX, suggesting the presence of the specific site for MTX-binding on the external surface of the cell membrane.

    Topics: Animals; Cricetinae; Glioma; Insulinoma; Ligands; Magnetic Resonance Spectroscopy; Marine Toxins; Molecular Structure; Oxocins; Rats; Tritium; Tumor Cells, Cultured

1992