Influence of Multidrug Resistance-Associated Proteins on the Excretion of the ABCC1 Imaging Probe 6-Bromo-7-[11C]Methylpurine in Mice

Molecular Imaging and Biology - Multidrug resistance-associated proteins (MRPs) mediate the hepatobiliary and renal excretion of many drugs and drug conjugates. The positron emission tomography...     

Model structure of the immunodominant surface antigen of <Emphasis Type="Italic">Eimeria tenella</Emphasis> identified as a target for sporozoite-neutralizing monoclonal antibody

Eimeria tenella is a coccidian parasite of great economical importance for poultry industry. The surface of Eimeria invasive agents, sporozoites and merozoites, is coated with a family of developmentally regulated glycosylphosphatidylinositol (GPI)-linked surface antigens (SAGs), some of them involved in the initiation of the infection process. Using 2D gel electrophoresis followed by mass spectrometry, an antigenic surface protein EtSAG1 (TA4) of E. tenella sporozoites has been identified as a target of neutralizing monoclonal antibody 2H10E3. To clarify the mechanism of invasion inhibition caused by the EtSAG1-specific antibodies, a structural model of EtSAG1 was generated. It appears that “EtSAG fold” does not bear an evolutionary relationship to any known protein structure. The intra- and interchain disulfide bonds could be assigned to certain pairs of six conserved cysteines found in members of the EtSAG protein family. The outward-facing surface of the antigen was found to comprise an expanded positively charged patch, thus suggesting that the parasite invasion process may be initiated by sporozoite attachment to negatively charged sulfated proteoglycans on the surface of the host cell.     

Extracellular calcium deficiency and ryanodine inhibit Eimeria tenella sporozoite invasion in vitro

An in vitro assay system with Eimeria tenella sporozoites was used to study the effects of extracellular calcium and active agents affecting the invasion of parasites into host cells. At concentrations of 900M Ca²⁺ and less the invasion rates were distinctly decreased. Ryanodine, a herbal alkaloid known for binding to internal Ca²⁺ channels (ryanodine receptors), showed an inhibitory effect on E. tenella sporozoite invasion. Preincubation tests and staining with a fluorescent derivative of ryanodine assured that the compound bound specifically to the sporozoites and affected them rather than the host cells.All experiments described in this publication comply with the current laws of Germany