Linked Life Data

19517454

Source:http://linkedlifedata.com/resource/pubmed/id/19517454

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2009-8-17
pubmed:abstractText
Enniatins (ENN) and beauvericin (BEA) exert cytotoxic properties. Here, we observed that their impact on Ca(2+)-homeostasis can be reversed by exogenous ATP. Thus, we investigated whether membrane-located ATP-binding cassette (ABC) transporters influence ENNs- and BEA-induced cytotoxicity. In short-term exposure assays breast cancer resistance protein (ABCG2)-overexpression weakly but significantly reduced the cytotoxic activity of BEA but not ENNs. In contrast, multidrug resistance-associated protein-1 (ABCC1)- and P-glycoprotein (ABCB1)-overexpression was not protective under identical conditions. ABCG2-mediated resistance against BEA was reversible by ABCG2 modulators. In long-term exposure assays, ABCG2 and ABCB1 significantly protected against ENNs- and to a lesser extent BEA-induced cytotoxicity. Moreover, both fusariotoxins potently inhibited the ABCG2- and ABCB1-mediated efflux of specific fluorescent substrates, with BEA being more effective. Additionally, ATPase and photoaffinity-labelling assays proofed interaction of both substances with ABCG2 and ABCB1. Remarkably, 2 years selection of KB-3-1 cells against both fusariotoxins resulted only in two-fold ENNs but negligible BEA resistance. Interestingly, the selected sublines displayed upregulation of multidrug resistance proteins and crossresistance to other chemotherapeutics. Summarizing, ABCG2 and ABCB1 slightly but significantly protect human cells against ENNs- and BEA-induced cytotoxicity. However, both mycotoxins potently interact with ABCB1 and ABCG2 transport functions suggesting influences on bioavailability of xenobiotics and pharmaceuticals.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/ABCB1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/ABCG2 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/ATP-Binding Cassette Transporters, http://linkedlifedata.com/resource/pubmed/chemical/Calcium, http://linkedlifedata.com/resource/pubmed/chemical/Depsipeptides, http://linkedlifedata.com/resource/pubmed/chemical/Multidrug Resistance-Associated..., http://linkedlifedata.com/resource/pubmed/chemical/Mycotoxins, http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins, http://linkedlifedata.com/resource/pubmed/chemical/P-Glycoprotein, http://linkedlifedata.com/resource/pubmed/chemical/beauvericin, http://linkedlifedata.com/resource/pubmed/chemical/enniatins, http://linkedlifedata.com/resource/pubmed/chemical/multidrug resistance-associated...
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1613-4133
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
53
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
904-20
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Interactions between ABC-transport proteins and the secondary Fusarium metabolites enniatin and beauvericin.
pubmed:affiliation
Department of Pharmacology and Toxicology, University of Vienna, Vienna, Austria.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't