Expression of alternative oxidase inhibits programmed cell death-like phenomenon in bloodstream form of Trypanosoma brucei rhodesiense

2005 ◽  
Vol 54 (4) ◽  
pp. 243-251 ◽  
Author(s):  
Akiko Tsuda ◽  
William H. Witola ◽  
Kazuhiko Ohashi ◽  
Misao Onuma
2005 ◽  
Vol 12 (4) ◽  
pp. 335-346 ◽  
Author(s):  
K Figarella ◽  
M Rawer ◽  
N L Uzcategui ◽  
B K Kubata ◽  
K Lauber ◽  
...  

2010 ◽  
Vol 6 (1) ◽  
pp. e1000731 ◽  
Author(s):  
Hanoch Goldshmidt ◽  
Devorah Matas ◽  
Anat Kabi ◽  
Shai Carmi ◽  
Ronen Hope ◽  
...  

1995 ◽  
Vol 312 (2) ◽  
pp. 479-484 ◽  
Author(s):  
E A C Wiemer ◽  
P A M Michels ◽  
F R Opperdoes

The pyruvate produced by glycolysis in the bloodstream form of the trypanosome is excreted into the host bloodstream by a facilitated diffusion carrier. The sensitivity of pyruvate transport for alpha-cyano-4-hydroxycinnamate and the compound UK5099 [alpha-cyano-beta-(1-phenylindol-3-yl)acrylate], which are known to be selective inhibitors of pyruvate (monocarboxylate) transporters present in mitochondria and the plasma membrane of eukaryotic cells, was examined. The trypanosomal pyruvate carrier was found to be rather insensitive to inhibition by alpha-cyano-4-hydroxycinnamate (Ki = 17 mM) but could be completely blocked by UK5099 (Ki = 49 microM). Inhibition of pyruvate transport resulted in the retention, and concomitant accumulation, of pyruvate within the trypanosomes, causing acidification of the cytosol and osmotic destabilization of the cells. Our results indicate that this physiological state has serious metabolic consequences and ultimately leads to cell death; thereby identifying the pyruvate carrier as a possible target for chemotherapeutic intervention.


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