Non-antisense cellular responses to oligonucleotides.
Oligonucleotides induce various cellular responses which are not due to the blockade of protein synthesis by an antisense mechanism. Oligonucleotides presenting double-stranded or G-quartet structures (ribo- or deoxyribonucleotides, phosphodiester or phosphorothioated) induce retraction of neurites and aggregation of chicken retinal cells within 10-20 h. This effect is reversible, non-toxic; it appears to require internalization and can be mimicked by treatment of the cells with an RGDS peptide. The oligonucleotides appear to trigger a cascade of intracellular events, affecting the adhesive properties of integrins. In addition, a subset of oligonucleotides induced platelet aggregation, probably through their interaction with membrane receptors. Recognition of these effects is important for the design and interpretation of antisense experiments.
Anselmet
Alain
A
CNRS UMR 8544, Laboratoire de Neurobiologie, Ecole Normale Supérieure, Paris, France. anselmet@biologie.ens.fr
Mayat
Ebrahim
E
Wietek
Stefan
S
Layer
Paul G
PG
Payrastre
Bernard
B
Massoulié
Jean
J
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002449:Cell Aggregation / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D006801:Humans; D016023:Integrins / Q000378:metabolism; D007424:Intracellular Fluid / Q000378:metabolism; D016501:Neurites / Q000187:drug effects; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000493:pharmacokinetics / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology; D010455:Peptides; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D012160:Retina / Q000166:cytology / Q000187:drug effects* / Q000196:embryology; D014162:Transfection
D016023:Integrins; D009841:Oligonucleotides; D009842:Oligopeptides; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; C046617:arginyl-glycyl-aspartyl-serine; D002118:Calcium