Cytotoxic Lipopeptide Muscotoxin A, Isolated from Soil Cyanobacterium Desmonostoc muscorum, Permeabilizes Phospholipid Membranes by Reducing Their Fluidity
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60077344%3A_____%2F15%3A00445230" target="_blank" >RIV/60077344:_____/15:00445230 - isvavai.cz</a>
Nalezeny alternativní kódy
RIV/61388971:_____/15:00445230 RIV/61388955:_____/15:00445230 RIV/60076658:12310/15:43888976 RIV/00216208:11310/15:10314267
Výsledek na webu
<a href="http://dx.doi.org/10.1021/tx500382b" target="_blank" >http://dx.doi.org/10.1021/tx500382b</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/tx500382b" target="_blank" >10.1021/tx500382b</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Cytotoxic Lipopeptide Muscotoxin A, Isolated from Soil Cyanobacterium Desmonostoc muscorum, Permeabilizes Phospholipid Membranes by Reducing Their Fluidity
Popis výsledku v původním jazyce
There is mounting evidence that cyanobacterial lipopeptides can kill mammalian cells, presenting a hazard to human health. Unfortunately, their mechanism of toxicity is poorly understood. We have isolated new cyclic undeca-lipopeptides muscotoxin A and B containing unique lipophilic residue 3-amino-2,5-dihydroxydecanoic acid (5-OH Ahdoa). Muscotoxin B was not used for biological studies due to its poor yield. Muscotoxin A was cytotoxic to YAC-1, Sp/2, and HeLa cancer cell lines (LC50 ranged from 9.9 to 13.2 mu M after 24 h of exposure), causing membrane damage and influx of calcium ions. Subsequently, we studied this lytic mechanism using synthetic liposomes with encapsulated fluorescent probes. Muscotoxin A permeabilized liposomes composed exclusively of phospholipids, demonstrating that no proteins or carbohydrates present in biomembranes are essential for its activity. Paradoxically, the permeabilization activity of muscotoxin A was mediated by a significant reduction in membrane surface fluidity (stiffening), the opposite of that caused by synthetic detergents and cytolytic lipopeptide puwainaphycin F. At 25 degrees C, muscotoxin A disrupted liposomes with and without cholesterol/sphingomyelin; however, at 37 degrees C, it was selective against liposomes with cholesterol/sphingomyelin. It appears that both membrane fluidity and organization can affect the lytic activity of muscotoxin A. Our findings strengthen the evidence that cyanobacterial lipopeptides specifically disrupt mammalian cell membranes and bring new insights into the mechanism of this effect.
Název v anglickém jazyce
Cytotoxic Lipopeptide Muscotoxin A, Isolated from Soil Cyanobacterium Desmonostoc muscorum, Permeabilizes Phospholipid Membranes by Reducing Their Fluidity
Popis výsledku anglicky
There is mounting evidence that cyanobacterial lipopeptides can kill mammalian cells, presenting a hazard to human health. Unfortunately, their mechanism of toxicity is poorly understood. We have isolated new cyclic undeca-lipopeptides muscotoxin A and B containing unique lipophilic residue 3-amino-2,5-dihydroxydecanoic acid (5-OH Ahdoa). Muscotoxin B was not used for biological studies due to its poor yield. Muscotoxin A was cytotoxic to YAC-1, Sp/2, and HeLa cancer cell lines (LC50 ranged from 9.9 to 13.2 mu M after 24 h of exposure), causing membrane damage and influx of calcium ions. Subsequently, we studied this lytic mechanism using synthetic liposomes with encapsulated fluorescent probes. Muscotoxin A permeabilized liposomes composed exclusively of phospholipids, demonstrating that no proteins or carbohydrates present in biomembranes are essential for its activity. Paradoxically, the permeabilization activity of muscotoxin A was mediated by a significant reduction in membrane surface fluidity (stiffening), the opposite of that caused by synthetic detergents and cytolytic lipopeptide puwainaphycin F. At 25 degrees C, muscotoxin A disrupted liposomes with and without cholesterol/sphingomyelin; however, at 37 degrees C, it was selective against liposomes with cholesterol/sphingomyelin. It appears that both membrane fluidity and organization can affect the lytic activity of muscotoxin A. Our findings strengthen the evidence that cyanobacterial lipopeptides specifically disrupt mammalian cell membranes and bring new insights into the mechanism of this effect.
Klasifikace
Druh
J<sub>x</sub> - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)
CEP obor
EE - Mikrobiologie, virologie
OECD FORD obor
—
Návaznosti výsledku
Projekt
Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.
Návaznosti
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Ostatní
Rok uplatnění
2015
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Chemical Research in Toxicology
ISSN
0893-228X
e-ISSN
—
Svazek periodika
28
Číslo periodika v rámci svazku
2
Stát vydavatele periodika
US - Spojené státy americké
Počet stran výsledku
9
Strana od-do
216-224
Kód UT WoS článku
000349656100008
EID výsledku v databázi Scopus
2-s2.0-84945361419