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  • 1
    Language: English
    In: Journal of Biosciences, Dec, 2007, Vol.32(3), p.1281(9)
    Description: Byline: Ralph H. Schaloske (1), Dagmar Blaesius (2), Christina Schlatterer (3), Daniel F. Lusche (4) Keywords: Arachidonic acid; chemotaxis; fatty acids; iplA Abstract: Cyclic AMP (cAMP) is a natural chemoattractant of the social amoeba Dictyostelium discoideum. It is detected by cell surface cAMP receptors. Besides a signalling cascade involving phosphatidylinositol 3,4,5-trisphosphate (PIP.sub.3), Ca.sup.2+ signalling has been shown to have a major role in chemotaxis. Previously, we have shown that arachidonic acid (AA) induces an increase in the cytosolic Ca.sup.2+ concentration by causing the release of Ca.sup.2+ from intracellular stores and activating influx of extracellular Ca.sup.2+. Here we report that AA is a chemoattractant for D. discoideum cells differentiated for 8--9 h. Motility towards a glass capillary filled with an AA solution was dose-dependent and qualitatively comparable to cAMP-induced chemotaxis. Ca.sup.2+ played an important role in AA chemotaxis of wild-type Ax2 as ethyleneglycolbis(b-aminoethyl)-N,N,N ,N -tetraacetic acid (EGTA) added to the extracellular buffer strongly inhibited motility. In the HM1049 mutant whose iplA gene encoding a putative Ins(1,4,5)P.sub.3-receptor had been knocked out, chemotaxis was only slightly affected by EGTA. Chemotaxis in the presence of extracellular Ca.sup.2+ was similar in both strains. Unlike cAMP, addition of AA to a cell suspension did not change cAMP or cGMP levels. A model for AA chemotaxis based on the findings in this and previous work is presented. Author Affiliation: (1) Department of Chemistry and Biochemistry, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0601, USA (2) Pharmaceutical Institute, Universty of Tuebingen, Morgenstelle 8, 72076, Tuebingen, Germany (3) Department of Biology, University of Konstanz, Universitaetsstr.10, 78457, Konstanz, Germany (4) W M Keck Dynamic Image Analysis Facility, Department of Biological Sciences, The University of Iowa, Iowa City, IA, 52242, USA Article History: Registration Date: 06/05/2007 Received Date: 02/05/2007 Accepted Date: 01/09/2007 Online Date: 07/05/2008 Article note: These authors contributed equally to this work. This work was carried out at the University of Konstanz, Department of Biology, Universitaetstr.10, 78457 Konstanz, Germany.
    Keywords: Arachidonic Acid -- Health Aspects ; Arachidonic Acid -- Research ; Chemotaxis -- Health Aspects ; Chemotaxis -- Research ; Dictyostelium -- Health Aspects ; Dictyostelium -- Research
    ISSN: 0250-5991
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  • 2
    Language: English
    In: Angewandte Chemie International Edition, 08 March 2010, Vol.49(11), pp.2045-2049
    Description: , commercially available or known compounds are connected to form myrtucommulone A, an anti‐inflammatory and apoptosis‐inducing substance from the common myrtle (see scheme). This strategy can be used, as well to prepare myrtucommulone libraries.
    Keywords: Alkylation ; Apoptosis ; Michael Addition ; Natural Products ; Total Synthesis
    ISSN: 1433-7851
    E-ISSN: 1521-3773
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  • 3
    Language: German
    In: Angewandte Chemie, 08 March 2010, Vol.122(11), pp.2089-2093
    Description: wird Myrtucommulon A, ein entzündungshemmender und Apoptose induzierender Inhaltsstoff der gemeinen Myrte , aus käuflichen oder literaturbekannten Verbindungen synthetisiert (siehe Schema). Die Synthesestrategie ermöglicht ebenfalls die Erzeugung von Myrtucommulon‐Bibliotheken.
    Keywords: Apoptose ; Alkylierungen ; Michael‐Additionen ; Naturstoffe ; Totalsynthesen
    ISSN: 0044-8249
    E-ISSN: 1521-3757
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  • 4
    Language: English
    In: Journal of biosciences, 2007, Vol.32(Supplement), pp.1281-1289
    Description: Cyclic AMP (cAMP) is a natural chemoattractant of the social amoeba Dictyostelium discoideum. It is detected by cell surface cAMP receptors. Besides a signalling cascade involving phosphatidylinositol 3,4,5-trisphosphate (PIP₃), Ca²⁺ signalling has been shown to have a major role in chemotaxis. Previously, we have shown that arachidonic acid (AA) induces an increase in the cytosolic Ca²⁺ concentration by causing the release of Ca²⁺ from intracellular stores and activating influx of extracellular Ca²⁺. Here we report that AA is a chemoattractant for D. discoideum cells differentiated for 8–9 h. Motility towards a glass capillary filled with an AA solution was dose-dependent and qualitatively comparable to cAMP-induced chemotaxis. Ca²⁺ played an important role in AA chemotaxis of wild-type Ax2 as ethyleneglycolbis(b-aminoethyl)-N,N,N′,N′-tetraacetic acid (EGTA) added to the extracellular buffer strongly inhibited motility. In the HM1049 mutant whose iplA gene encoding a putative Ins(1,4,5)P₃-receptor had been knocked out, chemotaxis was only slightly affected by EGTA. Chemotaxis in the presence of extracellular Ca²⁺ was similar in both strains. Unlike cAMP, addition of AA to a cell suspension did not change cAMP or cGMP levels. A model for AA chemotaxis based on the findings in this and previous work is presented. ; p. 1281-1289.
    Keywords: Dictyostelium Discoideum ; Calcium ; Adenosine Monophosphate ; Cyclic Gmp ; Genes ; Chemoattractants ; Receptors ; Calcium Signaling ; Chemotaxis ; Mutants ; Models ; Dose Response ; Cyclic Amp ; Ethylene Glycol Tetraacetic Acid ; Arachidonic Acid
    ISSN: 0250-5991
    Source: AGRIS (Food and Agriculture Organization of the United Nations)
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  • 5
    Language: English
    In: Journal of Biosciences, 2007, Vol.32(Supplement 3), pp.1281-1289
    Description: Cyclic AMP (cAMP) is a natural chemoattractant of the social amoeba Dictyostelium discoideum . It is detected by cell surface cAMP receptors. Besides a signalling cascade involving phosphatidylinositol 3,4,5-trisphosphate (PIP 3 ), Ca 2+ signalling has been shown to have a major role in chemotaxis. Previously, we have shown that arachidonic acid (AA) induces an increase in the cytosolic Ca 2+ concentration by causing the release of Ca 2+ from intracellular stores and activating influx of extracellular Ca 2+ . Here we report that AA is a chemoattractant for D. discoideum cells differentiated for 8–9 h. Motility towards a glass capillary filled with an AA solution was dose-dependent and qualitatively comparable to cAMP-induced chemotaxis. Ca 2+ played an important role in AA chemotaxis of wild-type Ax2 as ethyleneglycolbis(b-aminoethyl)-N,N,N′,N′-tetraacetic acid (EGTA) added to the extracellular buffer strongly inhibited motility. In the HM1049 mutant whose iplA gene encoding a putative Ins(1,4,5)P 3 -receptor had been knocked out, chemotaxis was only slightly affected by EGTA. Chemotaxis in the presence of extracellular Ca 2+ was similar in both strains. Unlike cAMP, addition of AA to a cell suspension did not change cAMP or cGMP levels. A model for AA chemotaxis based on the findings in this and previous work is presented.
    Keywords: Arachidonic acid ; chemotaxis ; fatty acids ; iplA
    ISSN: 0250-5991
    E-ISSN: 0973-7138
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  • 6
    Language: English
    In: Apoptosis, 2008, Vol.13(1), pp.119-131
    Description: Myrtucommulone (MC) is a unique, nonprenylated acylphloroglucinol contained in the leaves of myrtle ( Myrtus communis ). Here, we addressed the potential of MC to induce apoptosis of cancer cells. MC potently induced cell death of different cancer cell lines (EC 50 3–8 μM) with characteristics of apoptosis, visualized by the activation of caspase-3, -8 and -9, cleavage of poly(ADP-ribose)polymerase (PARP), release of nucleosomes into the cytosol, and DNA fragmentation. MC was much less cytotoxic for non-transformed human peripheral blood mononuclear cells (PBMC) or foreskin fibroblasts (EC 50 cell death = 20–50 μM), and MC up to 30 μM hardly caused processing of PARP, caspase-3, -8 and -9 in human PBMC. MC-induced apoptosis was mediated by the intrinsic rather than the extrinsic death pathway. Thus, MC caused loss of the mitochondrial membrane potential in MM6 cells and evoked release of cytochrome c from mitochondria. Interestingly, Jurkat cells deficient in caspase-9 were resistant to MC-induced cell death and no processing of PARP or caspase-8 was evident. In cell lines deficient in either CD95 (Fas, APO-1) signalling, FADD or caspase-8, MC was still able to potently induce cell death and PARP cleavage. Conclusively, MC induces apoptosis in cancer cell lines, with marginal cytotoxicity for non-transformed cells, via the mitochondrial cytochrome c/Apaf-1/caspase-9 pathway.
    Keywords: Cancer ; Apoptosis ; Mitochondria ; Caspase ; Myrtucommulone
    ISSN: 1360-8185
    E-ISSN: 1573-675X
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  • 7
    Language: English
    Description: Tübingen, Univ., Diss., 2009
    Source: Networked Digital Library of Theses and Dissertations
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