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  • Puwainaphycins F and G, moderate cytotoxins, which cause necrotic cell death to mammalian cells, were isolated from the soil cyanobacterium Cylindrospermum alatosporum C24/89. Both compounds have been shown to be cyclic decapeptides containing unusual beta-amino fatty acid (2-hydroxy-3-amino-4methyl tetradecanoic acid). Described variants differ in the substitution of threonine by glutamine in the fourth position. Their structures differ from the known puwainaphycins in five amino acids positions as well as in the beta-amino fatty acid unit. The rapid interaction of these compounds with the plasma membrane of the mammal cell leads to an elevation of the concentration of intracellular Ca2+, with kinetics comparable to the well-established calcium ionophore ionomycin. Subsequently, the induction of tyrosine phosphorylation was observed to be followed by the unique transformation of the actin cytoskeleton into ring structures around the nuclei. All of these alterations in the cellular morphology and physiology result in necrotic cell death after ca. 10 h. The IC50 values were determined to be 2.2 mu M for both puwainaphycins. The present data demonstrate the interaction of cyanobacterial secondary metabolites with eukaryotic plasma membrane and point out the possible toxic effects of cyanobacterial lipopeptides for humans.
  • Puwainaphycins F and G, moderate cytotoxins, which cause necrotic cell death to mammalian cells, were isolated from the soil cyanobacterium Cylindrospermum alatosporum C24/89. Both compounds have been shown to be cyclic decapeptides containing unusual beta-amino fatty acid (2-hydroxy-3-amino-4methyl tetradecanoic acid). Described variants differ in the substitution of threonine by glutamine in the fourth position. Their structures differ from the known puwainaphycins in five amino acids positions as well as in the beta-amino fatty acid unit. The rapid interaction of these compounds with the plasma membrane of the mammal cell leads to an elevation of the concentration of intracellular Ca2+, with kinetics comparable to the well-established calcium ionophore ionomycin. Subsequently, the induction of tyrosine phosphorylation was observed to be followed by the unique transformation of the actin cytoskeleton into ring structures around the nuclei. All of these alterations in the cellular morphology and physiology result in necrotic cell death after ca. 10 h. The IC50 values were determined to be 2.2 mu M for both puwainaphycins. The present data demonstrate the interaction of cyanobacterial secondary metabolites with eukaryotic plasma membrane and point out the possible toxic effects of cyanobacterial lipopeptides for humans. (en)
Title
  • The Cyanobacterial Cyclic Lipopeptides Puwainaphycins F/G Are Inducing Necrosis via Cell Membrane Permeabilization and Subsequent Unusual Actin Relocalization
  • The Cyanobacterial Cyclic Lipopeptides Puwainaphycins F/G Are Inducing Necrosis via Cell Membrane Permeabilization and Subsequent Unusual Actin Relocalization (en)
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  • The Cyanobacterial Cyclic Lipopeptides Puwainaphycins F/G Are Inducing Necrosis via Cell Membrane Permeabilization and Subsequent Unusual Actin Relocalization
  • The Cyanobacterial Cyclic Lipopeptides Puwainaphycins F/G Are Inducing Necrosis via Cell Membrane Permeabilization and Subsequent Unusual Actin Relocalization (en)
skos:notation
  • RIV/60076658:12310/12:43883519!RIV13-MSM-12310___
http://linked.open...avai/riv/aktivita
http://linked.open...avai/riv/aktivity
  • I, P(1M0506), P(ED2.1.00/03.0110), V, Z(AV0Z50200510), Z(AV0Z60660521), Z(MSM0021620858)
http://linked.open...iv/cisloPeriodika
  • 6
http://linked.open...vai/riv/dodaniDat
http://linked.open...aciTvurceVysledku
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http://linked.open...iv/duvernostUdaju
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http://linked.open...dnocenehoVysledku
  • 129332
http://linked.open...ai/riv/idVysledku
  • RIV/60076658:12310/12:43883519
http://linked.open...riv/jazykVysledku
http://linked.open.../riv/klicovaSlova
  • SEPARATION; MICROCYSTIS; REARRANGEMENT; DERIVATIZATION; PEPTIDES; LYNGBYA SP; ATP DEPLETION; PAHAYOKOLIDE-A; PROTEIN PHOSPHATASE-1; HEPTAFLUOROBUTYL CHLOROFORMATE (en)
http://linked.open.../riv/klicoveSlovo
http://linked.open...odStatuVydavatele
  • US - Spojené státy americké
http://linked.open...ontrolniKodProRIV
  • [B9B993A1D475]
http://linked.open...i/riv/nazevZdroje
  • CHEMICAL RESEARCH IN TOXICOLOGY
http://linked.open...in/vavai/riv/obor
http://linked.open...ichTvurcuVysledku
http://linked.open...cetTvurcuVysledku
http://linked.open...vavai/riv/projekt
http://linked.open...UplatneniVysledku
http://linked.open...v/svazekPeriodika
  • 25
http://linked.open...iv/tvurceVysledku
  • Hrouzek, Pavel
  • Kopecký, Jiří
  • Kuzma, Marek
  • Novák, Petr
  • Černý, Jan
  • Šimek, Petr
  • Lukesova, Alena
  • Fiser, Radovan
http://linked.open...ain/vavai/riv/wos
  • 000305300100006
http://linked.open...n/vavai/riv/zamer
issn
  • 0893-228X
number of pages
http://bibframe.org/vocab/doi
  • 10.1021/tx300044t
http://localhost/t...ganizacniJednotka
  • 12310
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