The Experts below are selected from a list of 285 Experts worldwide ranked by ideXlab platform
Takeshi Yasumoto - One of the best experts on this subject based on the ideXlab platform.
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Ca-dependent excitatory action of Maitotoxin, one of the principal toxin isolated from poisonous fishes in tropical seas,in the guinea-pig vas deferens
Japanese Journal of Pharmacology, 2019Co-Authors: Yasushi Ohizumi, Akiko Kajiwara, Takeshi YasumotoAbstract:Abstract A number of marine toxins have been extensively studied by numerous investigators and have proven to be very useful as tools for pharmacological studies. Recently it has been revealed that Maitotoxin (MTX) isolated from poisonous fishes is the most potent marine toxin known and that its minimum lethal dose in mice is 0.17 μg/kg (ip).
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Maitotoxin, a calcium channel activator, increases prolactin release from rat pituitary tumor 7315a cells by a mechanism that may involve leukotriene production.
Neuroendocrinology, 2008Co-Authors: Koji Koike, Takeshi Yasumoto, Ivan S Login, Allan M Judd, Robert M MacleodAbstract:Arachidonate and its metabolites may play an important role in the release of prolactin. In the present study, the effect of Maitotoxin, a calcium channel activator, was measured on the release of ara
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Histopathological studies of experimental marine toxin poisoning. II. The acute effects of Maitotoxin on the stomach, heart and lymphoid tissues in mice and rats
Toxicon, 2002Co-Authors: Kiyoshi Terao, Akihiro Yokoyama, Yoshiharu Sakamaki, Kazuei Igarashi, Takeshi YasumotoAbstract:Abstract K. Terao , E. Ito , Y. Sakamaki , K. Igarashi , A. Yokoyama and T. Yasumoto . Histopathological studies of experimental marine toxin poisoning. II. The acute effects of Maitotoxin on the stomach, heart and lymphoid tissues in mice and rats. Toxicon26, 395 – 402, 1988. — Maitotoxin, one of the causative agents of ciguatera isolated from marine dinoflagellate, Gambierdiscus toxicus, induced severe pathomorphological changes in the stomach, heart and lymphoid tissues in mice and rats. Multiple erosions were observed in gastric mucosa accompanied by a marked increase in total calcium content 24 hr after i.p. injection of 200 or 400 ng/kg of Maitotoxin. In contrast, there was no close temporal association between the accumulation of calcium and the morphological appearance of dead cells in the heart and thymus. Within 30 min of administration of 200 or 400 ng/kg of Maitotoxin, a marked swelling was seen in the endothelial lining cells of blood capillaries between cardiac muscle fibers, followed by the cell death of the fibers. Injection of Maitotoxin at a dose of 200 ng/kg or higher also resulted in necrosis of lymphocytes in the cortex of the thymus at 4 hr and in the medulla at 8 hr.
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Histopathological studies on experimental marine toxin poisoning—4. Pathogenesis of experimental Maitotoxin poisoning
Toxicon, 2002Co-Authors: Kiyoshi Terao, Yasushi Ohizumi, Masaki Kobayashi, Kazuei Igarashi, Yoshimi Kakinuma, Takeshi YasumotoAbstract:Repeated injections of 45 ng/kg of Maitotoxin into the peritoneal cavities of male ICR mice resulted in marked atrophy of lymphoid tissues, a reduction of lymphocytes in the circulating blood, reduced immunoglobulin M in serum, and an increase of calcium content in the adrenal glands. A single injection of 200 ng/kg of Maitotoxin induced a marked increase in total calcium content of the adrenal glands as well as in plasma cortisol concentration (about seven times control) within 1 hr. In contrast, mice pretreated with CoCl2, a calcium channel inhibitor, and/or adrenalectomized mice, showed no discernible changes in the lymphoid tissues after repeated injections of Maitotoxin. It is thus suggested that Maitotoxin first stimulates calcium influx in the adrenal glands, which then causes the release of cortisol into the blood. The excess amount of cortisol in serum produces acute involution of the thymus and other lymphoid tissues.
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Antibodies to Maitotoxin elicited by immunization with toxin-fragment conjugates☆
Toxicon, 1996Co-Authors: Gary S. Bignami, David F. Waller, Takeshi YasumotoAbstract:G. S. Bignami, D. F. Waller and T. Yasumoto. Antibodies to Maitotoxin elicited by immunization with toxin-fragment conjugates. Toxicon 34, 1393-1397, 1996.-Maitotoxin is a water-soluble polyether toxin produced by the benthic dinoflagellate, Gambierdiscus toxicus. Toxin fragments generated by periodate oxidation were conjugated to keyhole limpet hemocyanin, and the resulting immunogens were used to elicit Maitotoxin-specific antibodies in mice. A competitive immunoassay developed with polyclonal IgG antibodies detected ∼3 nM purified Maitotoxin standard (IC 50 ∼ 13 nM; 45 ng/ml) but did not detect other polyether marine toxins. These are the first reported Maitotoxin-specific antibodies.
Tadashi Nakata - One of the best experts on this subject based on the ideXlab platform.
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convergent synthesis of the ent za b c d ring system of Maitotoxin
Organic Letters, 2017Co-Authors: Tatsuo Saito, Hiroyuki Koshino, Masayuki Morita, Mikiko Sodeoka, Tadashi NakataAbstract:Stereoselective synthesis of the ent-ZA′B′C′D′-ring system of Maitotoxin has been accomplished through a convergent strategy utilizing Suzuki–Miyaura cross coupling reaction of ZA′-ring alkylborane and C′D′-ring (Z)-vinyl iodide, and subsequent construction of the B′-ring by reduction of the O,S-acetal.
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stereoselective synthesis of Maitotoxin ghi ring system having a 1 2 diol side chain
Heterocycles, 2008Co-Authors: Masanori Nagatomo, Tadashi NakataAbstract:The stereoselective synthesis of Maitotoxin GHI-ring system having a 1,2-diol side chain was accomplished via successive SmI 2 -induced reductive cyclizations of β-alkoxyacrylate-aldehyde and optically active (E)-β- alkoxyvinylsulfoxide-aldehyde, dihydroxylation of α,β-unsaturated δ-lactone, and Sharpless asymmetric dihydroxylation of the side chain.
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synthetic studies on Maitotoxin 3 stereoselective synthesis of the bcde ring system
Organic Letters, 2008Co-Authors: Masanori Satoh, Hiroyuki Koshino, Tadashi NakataAbstract:The stereoselective synthesis of the BCDE-ring system of Maitotoxin has been accomplished through a two-directional strategy for the construction of polycyclic ether. The key reactions involve SmI2-induced double cyclization of a β-alkoxyacrylate and a double dihydroxylation for construction of the B- and E-rings.
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synthetic studies on Maitotoxin 1 stereoselective synthesis of the c d e f ring system having a side chain
Organic Letters, 2008Co-Authors: Masayuki Morita, Hiroyuki Koshino, Seishi Ishiyama, Tadashi NakataAbstract:The stereoselective synthesis of the Maitotoxin C′D′E′F′-ring system having a side chain has been accomplished through a convergent strategy. The key reactions include Horner-Wadsworth-Emmons coupling of the C′D′E′-ring and the side chain and subsequent construction of the F′-ring by silane reduction of dihydropyran.
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Synthetic Studies on Maitotoxin. 1. Stereoselective Synthesis of the C′D′E′F′-Ring System Having a Side Chain
Organic Letters, 2008Co-Authors: Masayuki Morita, Hiroyuki Koshino, Seishi Ishiyama, Tadashi NakataAbstract:The stereoselective synthesis of the Maitotoxin C′D′E′F′-ring system having a side chain has been accomplished through a convergent strategy. The key reactions include Horner-Wadsworth-Emmons coupling of the C′D′E′-ring and the side chain and subsequent construction of the F′-ring by silane reduction of dihydropyran.
William P Schilling - One of the best experts on this subject based on the ideXlab platform.
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Maitotoxin converts the plasmalemmal ca2 pump into a ca2 permeable nonselective cation channel
American Journal of Physiology-cell Physiology, 2009Co-Authors: William G Sinkins, Mark Estacion, Vikram Prasad, Monu Goel, Gary E Shull, Diana L Kunze, William P SchillingAbstract:Maitotoxin (MTX) activates Ca2+-permeable nonselective cation channels and causes a dramatic increase in cytosolic free Ca2+ concentration ([Ca2+]i) in every cell examined to date, but the molecula...
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Maitotoxin induced cell death cascade in bovine aortic endothelial cells divalent cation specificity and selectivity
American Journal of Physiology-cell Physiology, 2004Co-Authors: Brian J Wisnoskey, Mark Estacion, William P SchillingAbstract:The Maitotoxin (MTX)-induced cell death cascade in bovine aortic endothelial cells (BAECs), a model for Ca2+ overload-induced toxicity, reflects three sequential changes in plasmalemmal permeabilit...
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blockade of Maitotoxin induced endothelial cell lysis by glycine and l alanine
American Journal of Physiology-cell Physiology, 2003Co-Authors: Mark Estacion, William G Sinkins, Justin Weinberg, William P SchillingAbstract:The Maitotoxin (MTX)-induced cell death cascade in bovine aortic endothelial cells (BAECs) is a model for oncotic/necrotic cell death. The cascade is initiated by an increase in cytosolic free Ca2+...
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blockade of Maitotoxin induced oncotic cell death reveals zeiosis
BMC Physiology, 2002Co-Authors: Mark Estacion, William P SchillingAbstract:Background Maitotoxin (MTX) initiates cell death by sequentially activating 1) Ca2+ influx via non-selective cation channels, 2) uptake of vital dyes via formation of large pores, and 3) release of lactate dehydrogenase, an indication of cell lysis. MTX also causes formation of membrane blebs, which dramatically dilate during the cytolysis phase. To determine the role of phospholipase C (PLC) in the cell death cascade, U73122, a specific inhibitor of PLC, and U73343, an inactive analog, were examined on MTX-induced responses in bovine aortic endothelial cells.
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Maitotoxin-induced membrane blebbing and cell death in bovine aortic endothelial cells
BMC Physiology, 2001Co-Authors: Mark Estacion, William P SchillingAbstract:Background Maitotoxin, a potent cytolytic agent, causes an increase in cytosolic free Ca^2+ concentration ([Ca^2+]_i) via activation of Ca^2+-permeable, non-selective cation channels (CaNSC). Channel activation is followed by formation of large endogenous pores that allow ethidium and propidium-based vital dyes to enter the cell. Although activation of these cytolytic/oncotic pores, or COP, precedes release of lactate dehydrogenase, an indication of oncotic cell death, the relationship between CaNSC, COP, membrane lysis, and the associated changes in cell morphology has not been clearly defined. In the present study, the effect Maitotoxin on [Ca^2+]_i, vital dye uptake, lactate dehydrogenase release, and membrane blebbing was examined in bovine aortic endothelial cells. Results Maitotoxin produced a concentration-dependent increase in [Ca^2+]_i followed by a biphasic uptake of ethidium. Comparison of ethidium (M_w 314 Da), YO-PRO-1 (M_w 375 Da), and POPO-3 (M_w 715 Da) showed that the rate of dye uptake during the first phase was inversely proportional to molecular weight, whereas the second phase appeared to be all-or-nothing. The second phase of dye uptake correlated in time with the release of lactate dehydrogenase. Uptake of vital dyes at the single cell level, determined by time-lapse videomicroscopy, was also biphasic. The first phase was associated with formation of small membrane blebs, whereas the second phase was associated with dramatic bleb dilation. Conclusions These results suggest that Maitotoxin-induced Ca^2+ influx in bovine aortic endothelial cells is followed by activation of COP. COP formation is associated with controlled membrane blebbing which ultimately gives rise to uncontrolled bleb dilation, lactate dehydrogenase release, and oncotic cell death.
Michio Murata - One of the best experts on this subject based on the ideXlab platform.
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synthesis and biological evaluation of qrstuvwxyza domains of Maitotoxin
Journal of the American Chemical Society, 2014Co-Authors: K C Nicolaou, Michio Murata, Philipp Heretsch, Tsuyoshi Nakamura, Anna Rudo, Keiichi KonokiAbstract:The synthesis of QRSTUVWXYZA′ domains 7, 8, and 9 of the highly potent marine neurotoxin Maitotoxin (1), the largest secondary metabolite isolated to date, is described. The devised synthetic strategy entailed a cascade Takai–Utimoto ester olefination/ring closing metathesis to construct ring Y, a hydroxydithioketal cyclization/methylation sequence to cast ring X, a Horner–Wadsworth–Emmons coupling of WXYZA′ ketophosphonate 11 with QRSTU aldehyde 12 to form enone 10, and a reductive hydroxyketone ring closure to forge ring V. 2D NMR spectroscopic analysis and comparison of 13C chemical shifts with those of the corresponding carbons of Maitotoxin revealed close similarities supporting the originally assigned structure of this region of the natural product. Biological evaluations of various synthesized domains of Maitotoxin in this and previous studies from these laboratories led to fragment structure–activity relationships regarding their ability to inhibit Maitotoxin-elicited Ca2+ influx in rat C6 glioma ...
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synthesis and biological activity of the c d e f ring system of Maitotoxin
Journal of Organic Chemistry, 2014Co-Authors: Masahiro Kunitake, Michio Murata, Keiichi Konoki, Takahiro Oshima, Makoto Ebine, Kohei Torikai, Tohru OishiAbstract:Stereoselective synthesis of the C′D′E′F′ ring system of Maitotoxin was achieved starting from the E′ ring through successive formation of the D′ and C′ rings based on SmI2-mediated reductive cyclization. Construction of the F′ ring was accomplished via Suzuki–Miyaura cross-coupling with a side chain fragment and Pd(II)-catalyzed cyclization of an allylic alcohol. The C′D′E′F′ ring system inhibited Maitotoxin-induced Ca2+ influx in rat glioma C6 cells with an IC50 value of 59 μM.
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artificial ladder shaped polyethers that inhibit Maitotoxin induced ca2 influx in rat glioma c6 cells
Bioorganic & Medicinal Chemistry Letters, 2012Co-Authors: Tohru Oishi, Keiichi Konoki, Kohei Torikai, Nobuaki Matsumori, Futoshi Hasegawa, Rie Tamate, Michio MurataAbstract:Abstract 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 Ca2+ 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 Ca2+ influx that has ever been reported.
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convergent synthesis and biological activity of the wxyza b c ring system of Maitotoxin
Organic Letters, 2008Co-Authors: Tohru Oishi, Keiichi Konoki, Kohei Torikai, Nobuaki Matsumori, Futoshi Hasegawa, Michio MurataAbstract:The WXYZA′B′C′ ring system (1) of Maitotoxin (MTX) was synthesized in a convergent manner via successive coupling of the W, Z, and C′ ring fragments through construction of the XY and A′B′ ring systems. The synthetic segment 1 blocked the hemolytic activity elicited by MTX.
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complete structure of Maitotoxin
Journal of Synthetic Organic Chemistry Japan, 1997Co-Authors: Makoto Sasaki, Michio MurataAbstract:Maitotoxin (MTX, 1) is the most toxic and largest non-biopolymer known to date. The complete structural determination of MTX including the absolute configuration has been achieved recently. The relative configurations of the four acyclic portions (C1-C15, C35-C39, C63-C68, and C134-C142) were elucidated by (1) the extensive configurational analysis mainly using long-range carbon-proton coupling constants (2, 3JC, H), and (2) the stereoselective synthesis of the eight model compounds (2A-2D, 13, 27A, 27B, and 47) which were furnished with thus assigned relative configurations. The comparison of their 1H and 13C-NMR data with those for the corresponding portion of MTX evidently established the relative configuration from C1 to C138. The absolute configuration of the entire molecule was determined by the enantioselective synthesis and chiral gas chromatographic comparison with a degradated fragment (3, 4-dimethy1-6-hepten-1-o1) derived from the natural product, which involved two chiral centers at C138 and C139.The present results have revealed that the preferred conformation of an appropriately designed model compound with the correct configuration closely mimics that of the corresponding portion of MTX. Thus, we could deduce the overall conformation of MTX by assembling the preferred conformation of each model compound based on the NMR data.
Mark Estacion - One of the best experts on this subject based on the ideXlab platform.
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Maitotoxin converts the plasmalemmal ca2 pump into a ca2 permeable nonselective cation channel
American Journal of Physiology-cell Physiology, 2009Co-Authors: William G Sinkins, Mark Estacion, Vikram Prasad, Monu Goel, Gary E Shull, Diana L Kunze, William P SchillingAbstract:Maitotoxin (MTX) activates Ca2+-permeable nonselective cation channels and causes a dramatic increase in cytosolic free Ca2+ concentration ([Ca2+]i) in every cell examined to date, but the molecula...
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Maitotoxin induced cell death cascade in bovine aortic endothelial cells divalent cation specificity and selectivity
American Journal of Physiology-cell Physiology, 2004Co-Authors: Brian J Wisnoskey, Mark Estacion, William P SchillingAbstract:The Maitotoxin (MTX)-induced cell death cascade in bovine aortic endothelial cells (BAECs), a model for Ca2+ overload-induced toxicity, reflects three sequential changes in plasmalemmal permeabilit...
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blockade of Maitotoxin induced endothelial cell lysis by glycine and l alanine
American Journal of Physiology-cell Physiology, 2003Co-Authors: Mark Estacion, William G Sinkins, Justin Weinberg, William P SchillingAbstract:The Maitotoxin (MTX)-induced cell death cascade in bovine aortic endothelial cells (BAECs) is a model for oncotic/necrotic cell death. The cascade is initiated by an increase in cytosolic free Ca2+...
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blockade of Maitotoxin induced oncotic cell death reveals zeiosis
BMC Physiology, 2002Co-Authors: Mark Estacion, William P SchillingAbstract:Background Maitotoxin (MTX) initiates cell death by sequentially activating 1) Ca2+ influx via non-selective cation channels, 2) uptake of vital dyes via formation of large pores, and 3) release of lactate dehydrogenase, an indication of cell lysis. MTX also causes formation of membrane blebs, which dramatically dilate during the cytolysis phase. To determine the role of phospholipase C (PLC) in the cell death cascade, U73122, a specific inhibitor of PLC, and U73343, an inactive analog, were examined on MTX-induced responses in bovine aortic endothelial cells.
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Maitotoxin-induced membrane blebbing and cell death in bovine aortic endothelial cells
BMC Physiology, 2001Co-Authors: Mark Estacion, William P SchillingAbstract:Background Maitotoxin, a potent cytolytic agent, causes an increase in cytosolic free Ca^2+ concentration ([Ca^2+]_i) via activation of Ca^2+-permeable, non-selective cation channels (CaNSC). Channel activation is followed by formation of large endogenous pores that allow ethidium and propidium-based vital dyes to enter the cell. Although activation of these cytolytic/oncotic pores, or COP, precedes release of lactate dehydrogenase, an indication of oncotic cell death, the relationship between CaNSC, COP, membrane lysis, and the associated changes in cell morphology has not been clearly defined. In the present study, the effect Maitotoxin on [Ca^2+]_i, vital dye uptake, lactate dehydrogenase release, and membrane blebbing was examined in bovine aortic endothelial cells. Results Maitotoxin produced a concentration-dependent increase in [Ca^2+]_i followed by a biphasic uptake of ethidium. Comparison of ethidium (M_w 314 Da), YO-PRO-1 (M_w 375 Da), and POPO-3 (M_w 715 Da) showed that the rate of dye uptake during the first phase was inversely proportional to molecular weight, whereas the second phase appeared to be all-or-nothing. The second phase of dye uptake correlated in time with the release of lactate dehydrogenase. Uptake of vital dyes at the single cell level, determined by time-lapse videomicroscopy, was also biphasic. The first phase was associated with formation of small membrane blebs, whereas the second phase was associated with dramatic bleb dilation. Conclusions These results suggest that Maitotoxin-induced Ca^2+ influx in bovine aortic endothelial cells is followed by activation of COP. COP formation is associated with controlled membrane blebbing which ultimately gives rise to uncontrolled bleb dilation, lactate dehydrogenase release, and oncotic cell death.
