Cytotoxic Lipopeptide Muscotoxin A, Isolated from Soil Cyanobacterium Desmonostoc muscorum, Permeabilizes Phospholipid Membranes by Reducing Their Fluidity
The result's identifiers
Result code in 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>
Alternative codes found
RIV/61388971:_____/15:00445230 RIV/61388955:_____/15:00445230 RIV/60076658:12310/15:43888976 RIV/00216208:11310/15:10314267
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
Cytotoxic Lipopeptide Muscotoxin A, Isolated from Soil Cyanobacterium Desmonostoc muscorum, Permeabilizes Phospholipid Membranes by Reducing Their Fluidity
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
EE - Microbiology, virology
OECD FORD branch
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Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2015
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Chemical Research in Toxicology
ISSN
0893-228X
e-ISSN
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Volume of the periodical
28
Issue of the periodical within the volume
2
Country of publishing house
US - UNITED STATES
Number of pages
9
Pages from-to
216-224
UT code for WoS article
000349656100008
EID of the result in the Scopus database
2-s2.0-84945361419