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| Fältnamn | Indikatorer | Metadata |
|---|---|---|
| 000 | 02779naa a2200409 4500 | |
| 001 | oai:DiVA.org:uu-223572 | |
| 003 | SwePub | |
| 008 | 140422s2014 | |||||||||||000 ||eng| | |
| 024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-2235722 URI |
| 024 | 7 | a https://doi.org/10.1128/EC.00271-132 DOI |
| 040 | a (SwePub)uu | |
| 041 | a engb eng | |
| 042 | 9 SwePub | |
| 072 | 7 | a ref2 swepub-contenttype |
| 072 | 7 | a art2 swepub-publicationtype |
| 100 | 1 | a Lai, De-Hua4 aut |
| 245 | 1 0 | a Solanesyl Diphosphate Synthase, an Enzyme of the Ubiquinone Synthetic Pathway, Is Required throughout the Life Cycle of Trypanosoma brucei |
| 264 | 1 | c 2014 |
| 338 | a print2 rdacarrier | |
| 520 | a Ubiquinone 9 (UQ9), the expected product of the long-chain solanesyl diphosphate synthase of Trypanosoma brucei (TbSPPS), has a central role in reoxidation of reducing equivalents in the mitochondrion of T. brucei. The ablation of TbSPPS gene expression by RNA interference increased the generation of reactive oxygen species and reduced cell growth and oxygen consumption. The addition of glycerol to the culture medium exacerbated the phenotype by blocking its endogenous generation and excretion. The participation of TbSPPS in UQ synthesis was further confirmed by growth rescue using UQ with 10 isoprenyl subunits (UQ10). Furthermore, the survival of infected mice was prolonged upon the downregulation of TbSPPS and/or the addition of glycerol to drinking water. TbSPPS is inhibited by 1-[(n-oct-1-ylamino)ethyl] 1,1-bisphosphonic acid, and treatment with this compound was lethal for the cells. The findings that both UQ9 and ATP pools were severely depleted by the drug and that exogenous UQ10 was able to fully rescue growth of the inhibited parasites strongly suggest that TbSPPS and UQ synthesis are the main targets of the drug. These two strategies highlight the importance of TbSPPS for T. brucei, justifying further efforts to validate it as a new drug target. | |
| 700 | 1 | a Poropat, Estefania4 aut |
| 700 | 1 | a Pravia, Carlos4 aut |
| 700 | 1 | a Landoni, Malena4 aut |
| 700 | 1 | a Couto, Alicia S.4 aut |
| 700 | 1 | a Perez Rojo, Fernando G.4 aut |
| 700 | 1 | a Fuchs, Alicia G.4 aut |
| 700 | 1 | a Dubin, Marta4 aut |
| 700 | 1 | a Elingold, Igal4 aut |
| 700 | 1 | a Rodriguez, Juan B.4 aut |
| 700 | 1 | a Ferella, Marcelau Uppsala universitet,Mikrobiologi4 aut0 (Swepub:uu)marfe814 |
| 700 | 1 | a Esteva, Monica I.4 aut |
| 700 | 1 | a Bontempi, Esteban J.4 aut |
| 700 | 1 | a Lukes, Julius4 aut |
| 710 | 2 | a Uppsala universitetb Mikrobiologi4 org |
| 773 | 0 | t Eukaryotic Cellg 13:2, s. 320-328q 13:2<320-328x 1535-9778x 1535-9786 |
| 856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-223572 |
| 856 | 4 8 | u https://doi.org/10.1128/EC.00271-13 |
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