The cyanobacterial cyclic lipopeptides puwainaphycins F/G are inducing necrosis via cell membrane permeabilization and subsequent unusual actin relocalization
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
22551534
DOI
10.1021/tx300044t
Knihovny.cz E-zdroje
- MeSH
- aktiny chemie metabolismus MeSH
- buněčná smrt účinky léků MeSH
- HeLa buňky MeSH
- lidé MeSH
- lipopeptidy chemie izolace a purifikace farmakologie MeSH
- mikrofilamenta účinky léků metabolismus MeSH
- molekulární struktura MeSH
- nádorové buněčné linie MeSH
- permeabilita buněčné membrány účinky léků MeSH
- protinádorové látky chemie izolace a purifikace farmakologie MeSH
- screeningové testy protinádorových léčiv MeSH
- sinice chemie MeSH
- vápník metabolismus MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- aktiny MeSH
- lipopeptidy MeSH
- protinádorové látky MeSH
- puwainaphycin F MeSH Prohlížeč
- puwainaphycin G MeSH Prohlížeč
- vápník MeSH
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 β-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 β-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 Ca(2+), 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 IC(50) values were determined to be 2.2 μM 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.
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