Exploring the mode of action of ebselen in Trypanosoma brucei hexokinase inhibition.

Glycolysis is essential to Trypanosoma brucei, the causative agent of African sleeping sickness, suggesting enzymes in the pathway could be targets for drug development. Ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one, EbSe) was identified in a screen as a potent inhibitor of T. brucei hexokinase 1 (TbHK1), the first enzyme in the pathway.

Formation of Hirano bodies in Dictyostelium and mammalian cells induced by expression of a modified form of an actin-crosslinking protein.

We report the serendipitous development of the first cultured cell models of Hirano bodies. Myc-epitope-tagged forms of the 34 kDa actin bundling protein (amino acids 1-295) and the CT fragment (amino acids 124-295) of the 34 kDa protein that exhibits activated actin binding and calcium-insensitive actin filament crosslinking activity were expressed in Dictyostelium and mammalian cells to assess the behavior of these modified forms in vivo. Dictyostelium cells expressing the CT-myc fragment: (1) form ellipsoidal regions that contain ordered assemblies of F-actin, CT-myc, myosin II, cofilin and alpha-actinin; (2) grow and develop more slowly than wildtype, but produce normal morphogenetic structures; (3) perform pinocytosis and phagocytosis normally; and (4) produce a level of total actin equivalent to wildtype, but a higher level of F-actin.