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A Doody

Publications and source records attributed to A Doody.

3 recordsLinked to original sources
PubMed2006

RNA-interference effectors and their delivery.

RNA-interference, the mechanism by which the expression of a specific protein can be reduced or eliminated, has emerged as a potential way to treat disease. RNA-interference effectors, such as small interfering RNA and small hairpin RNA, are double-stranded nucleic acid sequences expressly designed to have homology to sections of the target protein's mRNA, and when present in the cytosol trigger hydrolysis of the mRNA through the RNA-interference pathway. Because RNA-interference effectors are macromolecular and typically polyanionic, their efficacy is poor when not accompanied by a delivery vehicle. This review outlines the RNA-interference mechanism and discusses the delivery of RNA-interference effectors, with an emphasis on synthetic polymer-based delivery systems.

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PubMed2001

Inhibition of transferrin recycling and endosome tubulation by phospholipase A2 antagonists.

We report here that a broad spectrum of phospholipase A(2) (PLA(2)) antagonists produce a concentration-dependent, differential block in the endocytic recycling pathway of transferrin (Tf) and Tf receptors (TfRs) but have no acute affect on Tf uptake from the cell surface. At low concentrations of antagonists (approximately 1 microm), Tf and TfR accumulated in centrally located recycling endosomes, whereas at higher concentrations (approximately 10 microm), Tf-TfR accumulated in peripheral sorting endosomes. Several independent lines of evidence suggest that this inhibition of recycling may result from the inhibition of tubule formation. First, BFA-stimulated endosome tubule formation was similarly inhibited by PLA(2) antagonists. Second, endocytosed tracers were found in larger spherical endosomes in the presence of PLA(2) antagonists. And third, endosome tubule formation in a cell-free, cytosol-dependent reconstitution system was equally sensitive PLA(2) antagonists. These results are consistent with the conclusion that endosome membrane tubules are formed by the action of a cytoplasmic PLA(2) and that PLA(2)-dependent tubules are involved in intracellular recycling of Tf and TfR. When taken together with previous studies on the Golgi complex, these results also indicate that an intracellular PLA(2) activity provides a novel molecular mechanism for inducing tubule formation from multiple organelles.

Animals↗