cytochalasin

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/01/06 09:55:54」(JST)

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Cytochalasins are fungal metabolites that have the ability to bind to actin filaments and block polymerization and the elongation of actin. As a result of the inhibition of actin polymerization, cytochalasins can change cellular morphology, inhibit cellular processes such as cell division, and even cause cells to undergo apoptosis.^[1] Cytochalasins have the ability to permeate cell membranes, prevent cellular translocation and cause cells to enucleate.^[2] Cytochalasins can also have an effect on other aspects of biological processes unrelated to actin polymerization. For example, cytochalasin A and cytochalasin B can also inhibit the transport of monosaccharides across the cell membrane,^[2] cytochalasin H has been found to regulate plant growth,^[3] cytochalasin D inhibits protein synthesis^[4] and cytochalasin E prevents angiogenesis.^[5]

Binding to actin filaments

Cytochalasins are known to bind to the barbed, fast growing plus ends of microfilaments, which then blocks both the assembly and disassembly of individual actin monomers from the bound end. Once bound, cytochalasins essentially cap the end of the new actin filament. One cytochalasin will bind to one actin filament.^[2] Studies done with cytochalasin D (CD) have found that the formation of CD-actin dimers, contain ATP-bound actin.^[6] These CD-actin dimers are reduced to CD-actin monomers as a result of ATP hydrolysis. The resulting CD-actin monomer can bind ATP-actin monomer to reform the CD-actin dimer.^[2] CD is very effective; only low concentrations (0.2 μM) are needed to prevent membrane ruffling and disrupt treadmilling.^[7] The effects of many different cytochalasins on actin filaments were analyzed and higher concentrations (2-20 μM) of CD were found to be needed to remove stress fibers.^[7]

In contrast, latrunculin inhibits actin filament polymerization by binding to actin monomers.

Uses and applications of cytochalasins

Actin microfilaments have been widely studied using cytochalasins. Due to their chemical nature, cytochalasins can help researchers understand the importance of actin in various biological processes. The use of cytochalasins has allowed researchers to better understand actin polymerization, cell motility, ruffling, cell division, contraction, and cell stiffness. The use of cytochalasins has been so important to understanding cytoskeletal movement and many other biological processes, researchers have created two synthetic cytochalasins.^[1]

Cytochalasin has found practical application in thromboelastometry (TEM) whole blood assays for the assessment of fibrinogen and fibrin polymerization disorders in the FIBTEM assay on ROTEM. This test is based on the principle that cytochalasin D very effectively inhibits platelet function by inhibition of the contractile elements.^[8] The platelet inhibition is more effective than when platelets are blocked by GPIIb/IIIa antagonists.^[9] In vitro and clinical data indicate that the clot strength in FIBTEM increases in a fibrinogen concentration-dependent manner independent of platelet count.^[10] Therefore fibrinogen deficiency or fibrin polymerization disorders can be rapidly detected.

Chemical structures

Cytochalasin A
Cytochalasin B
Cytochalasin C
Cytochalasin D
Cytochalasin E
Cytochalasin F
Cytochalasin H
Cytochalasin J

References

^ ^a ^b Haidle, A. M.; Myers, A. G. (2004). "An Enantioselective, Modular, and General Route to the Cytochalasins: Synthesis of L-696,474 and Cytochalasin B" (pdf). Proceedings of the National Academy of Sciences 101 (33): 12048–12053. doi:10.1073/pnas.0402111101. PMC 514432. PMID 15208404.
^ ^a ^b ^c ^d Cooper, J. A. (1987). "Effects of Cytochalasin and Phalloidin on Actin" (pdf). Journal of Cell Biology 105 (4): 1473–1478. doi:10.1083/jcb.105.4.1473. PMC 2114638. PMID 3312229.
^ Cox, R. H.; Cutler, H. G.; Hurd, R. E.; Cole, R. J. (1983). "Proton and Carbon-13 Nuclear Magnetic Resonance Studies of the Conformation of Cytochalasin H Derivatives and Plant Growth Regulating Effects of Cytochalasins". Journal of Agricultural and Food Chemistry 31 (2): 405–408. doi:10.1021/jf00116a055.
^ Ornelles, D. A.; Fey, E. G.; Penman, S. (1986). "Cytochalasin Releases mRNA from the Cytoskeletal Framework and Inhibits Protein Synthesis" (pdf). Molecular and Cellular Biology 6 (5): 1650–1662. PMC 367692. PMID 3785175.
^ Udagawa, T.; Yuan, J.; Panigrahy, D.; Chang, Y.-H.; Shah, J.; D’Amato, R. J. (2000). "Cytochalasin E, an Epoxide Containing Aspergillus-Derived Fungal Metabolite, Inhibits Angiogenesis and Tumor Growth" (pdf). Journal of Pharmacology and Experimental Therapeutics 294 (2): 421–427. PMID 10900214.
^ Goddette, D. W.; Frieden, C. (1987). "Actin Polymerization - The Mechanism of Action of Cytochalasin D" (pdf). Journal of Biological Chemistry 261 (34): 15974–15980. PMID 3023337.
^ ^a ^b Yahara, I.; Harada, F.; Sekita, S.; Yoshihira, K.; Natori, S. (1982). "Correlation between effects of 24 different cytochalasins on cellular structures and cellular events and those on actin in vitro" (pdf). Journal of Cell Biology 92 (1): 69–78. doi:10.1083/jcb.92.1.69. PMC 2112011. PMID 7199054.
^ May, J. A.; Ratan, H.; Glenn, J. R.; Lösche, W.; Spangenberg, P.; Heptinstall, S. (1998). "GPIIb-IIIa antagonists cause rapid disaggregation of platelets pretreated with cytochalasin D. Evidence that the stability of platelet aggregates depends on normal cytoskeletal assembly". Platelets 9 (3–4): 227–232. doi:10.1080/09537109876744. PMID 16793707.
^ Lang, T.; Toller, W.; Gütl, M.; Mahla, E.; Metzler, H.; Rehak, P.; März, W.; Halwachs-Baumann, G. (2004). "Different effects of abciximab and cytochalasin D on clot strength in thrombelastography" (pdf). Journal of Thrombosis and Haemostasis 2 (1): 147–153. doi:10.1111/j.1538-7836.2004.00555.x. PMID 14717978.
^ Lang, T.; Johanning, K.; Metzler, H.; Piepenbrock, S.; Solomon, C.; Rahe-Meyer, N.; Tanaka, K. A. (2009). "The effects of fibrinogen levels on thromboelastometric variables in the presence of thrombocytopenia" (pdf). Anesthesia and Analgesia 108 (3): 751–758. doi:10.1213/ane.0b013e3181966675. PMID 19224779.

English Journal

Management of severe bleeding in a ruptured extrauterine pregnancy: a theragnostic approach.

Grassetto A1, Fullin G, Cerri G, Simioni P, Spiezia L, Maggiolo C.Author information 1aUOC Anestesia e Rianimazione, Dipartimento Emergenza Urgenza, Ospedale dell'Angelo di Mestre, Venice, Italy bUOC Ostetricia e Ginecologia, Dipartimento Materno Infantile, Ospedale dell'Angelo di Mestre, Venice, Italy cDepartment of Cardiothoracic and Vascular Sciences, University Hospital of Padua, Italy.AbstractHaemoperitoneum due to ruptured extrauterine pregnancy is a complication that may occur in the first trimester of pregnancy, but massive haemorrhage with severe shock is rare. When severe bleeding does occur, timely diagnosis and rapid haemostatic treatment are vital. We present the case of a 37-year-old woman with severe bleeding and shock due to ruptured extrauterine pregnancy.Management of the patient consisted of emergency laparotomy, red blood cell transfusion and targeted haemostatic therapy guided by rotational thromboelastometry using the fibrin-based clotting (FIBTEM) assay, (activation with tissue factor with addition of the platelet inhibitor cytochalasin D). As severe hypofibrinogenaemia was apparent, indicated by a FIBTEM maximum clot firmness (MCF) that was not measurable (i.e. < 2 mm) and a plasma fibrinogen level of 0.17 g/l, the patient was treated with 4 g fibrinogen concentrate. Tranexamic acid (1 g) was also administered.Rapid restoration of haemostasis was indicated by the improvement of thromboelastometric parameters (FIBTEM MCF 16 mm) and, later, laboratory coagulation tests (plasma fibrinogen 2.75 g/l), along with cessation of bleeding. No fresh frozen plasma (FFP) was administered. Surgery was successfully completed, and the patient was subsequently discharged 5 days after admission with no further complications. Haemorrhage in extrauterine pregnancy is commonly managed using autologous blood transfusion (via cell salvage) and homologous plasma transfusion. In this case of severe bleeding and shock due to ruptured extrauterine pregnancy, thromboelastometry-guided administration of fibrinogen concentrate enabled rapid restoration of haemostasis, complete avoidance of FFP transfusion and resulted in a successful outcome.
Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis.Blood Coagul Fibrinolysis.2014 Mar;25(2):176-9. doi: 10.1097/MBC.0000000000000010.
Haemoperitoneum due to ruptured extrauterine pregnancy is a complication that may occur in the first trimester of pregnancy, but massive haemorrhage with severe shock is rare. When severe bleeding does occur, timely diagnosis and rapid haemostatic treatment are vital. We present the case of a 37-yea
PMID 24253241

Energy-dependent uptake of benzo[a]pyrene and its cytoskeleton-dependent intracellular transport by the telluric fungus Fusarium solani.

Fayeulle A1, Veignie E, Slomianny C, Dewailly E, Munch JC, Rafin C.Author information 1Unité de Chimie Environnementale et Interactions sur le Vivant UCEIV EA 4492, ULCO, Dunkerque, 59140, France.AbstractIn screening indigenous soil filamentous fungi for polycyclic aromatic hydrocarbons (PAHs) degradation, an isolate of the Fusarium solani was found to incorporate benzo[a]pyrene (BaP) into fungal hyphae before degradation and mineralization. The mechanisms involved in BaP uptake and intracellular transport remain unresolved. To address this, the incorporation of two PAHs, BaP, and phenanthrene (PHE) were studied in this fungus. The fungus incorporated more BaP into cells than PHE, despite the 400-fold higher aqueous solubility of PHE compared with BaP, indicating that PAH incorporation is not based on a simple diffusion mechanism. To identify the mechanism of BaP incorporation and transport, microscopic studies were undertaken with the fluorescence probes Congo Red, BODIPY®493/503, and FM®4-64, targeting different cell compartments respectively fungal cell walls, lipids, and endocytosis. The metabolic inhibitor sodium azide at 100 mM totally blocked BaP incorporation into fungal cells indicating an energy-requirement for PAH uptake into the mycelium. Cytochalasins also inhibited BaP uptake by the fungus and probably its intracellular transport into fungal hyphae. The perfect co-localization of BaP and BODIPY reveals that lipid bodies constitute the intracellular storage sites of BaP in F. solani. Our results demonstrate an energy-dependent uptake of BaP and its cytoskeleton-dependent intracellular transport by F. solani.
Environmental science and pollution research international.Environ Sci Pollut Res Int.2014 Mar;21(5):3515-23. doi: 10.1007/s11356-013-2324-3. Epub 2013 Nov 24.
In screening indigenous soil filamentous fungi for polycyclic aromatic hydrocarbons (PAHs) degradation, an isolate of the Fusarium solani was found to incorporate benzo[a]pyrene (BaP) into fungal hyphae before degradation and mineralization. The mechanisms involved in BaP uptake and intracellular tr
PMID 24271730

Absence of micronucleus formation in CHO-K1 cells cultivated in platelet lysate enriched medium.

Bernardi M1, Adami V2, Albiero E1, Madeo D3, Rodeghiero F1, Astori G4.Author information 1Hematology Project Foundation Research Laboratories, Contrà S. Francesco 41, Vicenza, Italy; Advanced Cellular Therapy Laboratory, Department of Cellular Therapy and Hematology, San Bortolo Hospital, Via Rodolfi 37, Vicenza, Italy.2High Throughput Screening Core Facility, CIBIO (Centre for Integrative Biology) - University of Trento, via delle Regole 101, Mattarello (TN), Italy.3Hematology Project Foundation Research Laboratories, Contrà S. Francesco 41, Vicenza, Italy.4Advanced Cellular Therapy Laboratory, Department of Cellular Therapy and Hematology, San Bortolo Hospital, Via Rodolfi 37, Vicenza, Italy. Electronic address: astori@hemato.ven.it.AbstractHuman platelet lysate (PL) represents an effective substitute of fetal bovine serum (FBS) for mesenchymal stromal cell (MSC) cultivation. Compared to FBS, PL favors MSC proliferation significantly shortening the population doubling time and avoiding the risks related to the use of animal derivatives. Growth factors contained in the platelets are released upon platelet disruption following freezing/thawing cycles or as we have recently described by using ultrasound. We have investigated whether the increased cell proliferation achieved by using PL could induce mitotic stress and whether the potential formation of free radicals during PL production by ultrasound could cause chromosomal instability in mammalian cells. We have applied an image analysis assisted high content screening (HCS) in vitro micronucleus assay in the Chinese Hamster Ovarian K1 (CHO-K1) rodent mammalian cell line. PL was produced by sonication; for the micronucleus assay, CHO-K1 cells were exposed to increasing concentrations of PL. Cytokinesis was blocked by cytochalasin B, nuclei were stained with bisbenzimide and images were acquired and analyzed automatically using an HCS system, both with a 20× and a 10× objective. Our results suggest that growth stimulus induced by the use of PL did not significantly increase micronucleus formation in CHO-K1 cells compared to negative control. Micronucleus testing in conjunction with HCS could represent a valid tool to evaluate the safety of ancillary materials used in the production of cell-based medicinal products.
Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie.Exp Toxicol Pathol.2014 Mar;66(2-3):111-6. doi: 10.1016/j.etp.2013.11.001. Epub 2013 Nov 28.
Human platelet lysate (PL) represents an effective substitute of fetal bovine serum (FBS) for mesenchymal stromal cell (MSC) cultivation. Compared to FBS, PL favors MSC proliferation significantly shortening the population doubling time and avoiding the risks related to the use of animal derivatives
PMID 24290702

Japanese Journal

Cytochalasin H, an Active Anti-Angiogenic Constituent of the Ethanol Extract of Gleditsia sinensis Thorns

Lee Jun,Yi Jin-Mu,Kim Haejin [他],Lee You Jin,Park Jong-Shik,Bang Ok-Sun,Kim No Soo
Biological and Pharmaceutical Bulletin, 6-12, 2014
… By virtue of in vitro activity-guided fractionation using human umbilical vein endothelial cells (HUVEC) primary endothelial cells, chromatographic separation, and NMR spectral analyses, we isolated and identified the potent active constituent, cytochalasin H, a biologically active secondary metabolite of fungi. …
NAID 130003382111

Biosynthetic assembly of cytochalasin backbone

Fujii Ryuya,Minami Atsushi,Gomi Katsuya,Oikawa Hideaki
Tetrahedron Letters 54(23), 2999-3002, 2013-06-05
… We have succeeded to heterologously express the cytochalasin polyketide synthase-non-ribosomal peptide synthetase (PKS-NRPS) hybrid gene ccsA and the trans-acting enoyl-CoA reductase gene ccsC in Aspergillus oryzae. … The resultant transformant produced a novel metabolite possessing the cytochalasin backbone. …
NAID 120005295657

Correlation between actin content and laser phase shift of adhesive normal and malignant prostate epithelial cells(CELL AND TISSUE ENGINEERING)

Takagi Mutsumi,Tokunaga Naochika
Journal of bioscience and bioengineering 115(3), 310-313, 2013-03
… The decrease in relative actin content by the addition of cytochalasin D resulted in the decrease in phase shift in both cell lines, and these cell lines showed a marked positive correlation between phase shift and relative actin content (r = 0.84). …
NAID 110009596106

Related Pictures

[Haidle-1] Haidle, A. M.; Myers, A. G. (2004). "An Enantioselective, Modular, and General Route to the Cytochalasins: Synthesis of L-696,474 and Cytochalasin B" (pdf). Proceedings of the National Academy of Sciences 101 (33): 12048–12053. doi:10.1073/pnas.0402111101. PMC 514432. PMID 15208404.

[Cooper-2] Cooper, J. A. (1987). "Effects of Cytochalasin and Phalloidin on Actin" (pdf). Journal of Cell Biology 105 (4): 1473–1478. doi:10.1083/jcb.105.4.1473. PMC 2114638. PMID 3312229.

[3] Cox, R. H.; Cutler, H. G.; Hurd, R. E.; Cole, R. J. (1983). "Proton and Carbon-13 Nuclear Magnetic Resonance Studies of the Conformation of Cytochalasin H Derivatives and Plant Growth Regulating Effects of Cytochalasins". Journal of Agricultural and Food Chemistry 31 (2): 405–408. doi:10.1021/jf00116a055.

[4] Ornelles, D. A.; Fey, E. G.; Penman, S. (1986). "Cytochalasin Releases mRNA from the Cytoskeletal Framework and Inhibits Protein Synthesis" (pdf). Molecular and Cellular Biology 6 (5): 1650–1662. PMC 367692. PMID 3785175.

[5] Udagawa, T.; Yuan, J.; Panigrahy, D.; Chang, Y.-H.; Shah, J.; D’Amato, R. J. (2000). "Cytochalasin E, an Epoxide Containing Aspergillus-Derived Fungal Metabolite, Inhibits Angiogenesis and Tumor Growth" (pdf). Journal of Pharmacology and Experimental Therapeutics 294 (2): 421–427. PMID 10900214.

[6] Goddette, D. W.; Frieden, C. (1987). "Actin Polymerization - The Mechanism of Action of Cytochalasin D" (pdf). Journal of Biological Chemistry 261 (34): 15974–15980. PMID 3023337.

[Yahara-7] Yahara, I.; Harada, F.; Sekita, S.; Yoshihira, K.; Natori, S. (1982). "Correlation between effects of 24 different cytochalasins on cellular structures and cellular events and those on actin in vitro" (pdf). Journal of Cell Biology 92 (1): 69–78. doi:10.1083/jcb.92.1.69. PMC 2112011. PMID 7199054.

[8] May, J. A.; Ratan, H.; Glenn, J. R.; Lösche, W.; Spangenberg, P.; Heptinstall, S. (1998). "GPIIb-IIIa antagonists cause rapid disaggregation of platelets pretreated with cytochalasin D. Evidence that the stability of platelet aggregates depends on normal cytoskeletal assembly". Platelets 9 (3–4): 227–232. doi:10.1080/09537109876744. PMID 16793707.

[9] Lang, T.; Toller, W.; Gütl, M.; Mahla, E.; Metzler, H.; Rehak, P.; März, W.; Halwachs-Baumann, G. (2004). "Different effects of abciximab and cytochalasin D on clot strength in thrombelastography" (pdf). Journal of Thrombosis and Haemostasis 2 (1): 147–153. doi:10.1111/j.1538-7836.2004.00555.x. PMID 14717978.

[10] Lang, T.; Johanning, K.; Metzler, H.; Piepenbrock, S.; Solomon, C.; Rahe-Meyer, N.; Tanaka, K. A. (2009). "The effects of fibrinogen levels on thromboelastometric variables in the presence of thrombocytopenia" (pdf). Anesthesia and Analgesia 108 (3): 751–758. doi:10.1213/ane.0b013e3181966675. PMID 19224779.

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