Mechanism of T. brucei Cell Cytotoxicity by Benzophenone-Derived Bisphophonium Salts

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60077344%3A_____%2F13%3A00488322" target="_blank" >RIV/60077344:_____/13:00488322 - isvavai.cz</a>

Výsledek na webu

<a href="http://www.parazitologie.cz/protozoologie/Protodny2013/JPD_sbornik_2013.pdf" target="_blank" >http://www.parazitologie.cz/protozoologie/Protodny2013/JPD_sbornik_2013.pdf</a>

DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Mechanism of T. brucei Cell Cytotoxicity by Benzophenone-Derived Bisphophonium Salts

Popis výsledku v původním jazyce

A recent report claims that succinate dehydrogenase, respiratory complex II (cII), is the target of a subset of benzophenone-derived bisphophonium salts that inhibit Leishmania donovani proliferation in a low micromolar concentration range. However, this was suggested from the interpretation of broad phenotypes in treated cells and indirect evidence. We show that these compounds are also very potent inhibitors of both the insect (PS) and mammalian (BS) life stage of Trypanosoma brucei. Since cII is not essential in either stage of T. brucei, we explored the mechanism of cell death in this very closely related parasite. RNAi knockdown cell lines of a critical subunit of cII was generated in both life stages and analyzed for growth phenotype, mitochondrial membrane potential, cII assembly and cII activity. Furthermore, wild type and cII RNAi induced T. brucei cells were treated with two of these compounds and then monitored for their effects on and cII activity. We propose that while these new trypanocidal drugs can directly inhibit cII, this is most likely not the major cause of cell death.n

Název v anglickém jazyce

Mechanism of T. brucei Cell Cytotoxicity by Benzophenone-Derived Bisphophonium Salts

Popis výsledku anglicky

A recent report claims that succinate dehydrogenase, respiratory complex II (cII), is the target of a subset of benzophenone-derived bisphophonium salts that inhibit Leishmania donovani proliferation in a low micromolar concentration range. However, this was suggested from the interpretation of broad phenotypes in treated cells and indirect evidence. We show that these compounds are also very potent inhibitors of both the insect (PS) and mammalian (BS) life stage of Trypanosoma brucei. Since cII is not essential in either stage of T. brucei, we explored the mechanism of cell death in this very closely related parasite. RNAi knockdown cell lines of a critical subunit of cII was generated in both life stages and analyzed for growth phenotype, mitochondrial membrane potential, cII assembly and cII activity. Furthermore, wild type and cII RNAi induced T. brucei cells were treated with two of these compounds and then monitored for their effects on and cII activity. We propose that while these new trypanocidal drugs can directly inhibit cII, this is most likely not the major cause of cell death.n

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/LL1205" target="_blank" >LL1205: Charakterizace unikátních vlastností esenciální FoF1 ATP syntázy u původce africké spavé nemoci Trypanosoma bucei za účelem vývoje inhibitorů tohoto komplexu.</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2013

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů