Chemotaxis and the synthesis of specific proteins are inhibited by 3-deazaadenosine and other adenosine analogs in a mouse macrophage cell line.
It has been shown earlier that 3-deazaadenosine but not 3-deazaaristeromycin inhibits chemotaxis of RAW264 cells (Aksamit, R.R., Falk, W., and Cantoni, G.L. (1982) J. Biol. Chem. 257, 621-625). We show here in RAW264 cells that (a) the incorporation of the methyl group of methionine into phosphatidylcholine is inhibited approximately 90% by both 3-deazaadenosine and 3-deazaaristeromycin, (b) 3-deazaadenosine but not 3-deazaaristeromycin inhibits the synthesis of specific proteins, and (c) 3'-deoxyadenosine and erythro-9-(2-hydroxy-3-nonyl)-adenine in the presence of adenosine and homocysteine inhibit chemotaxis and the synthesis of specific proteins. Inhibition of the synthesis of specific proteins can be observed only after the solubilized cellular proteins are separated by two-dimensional polyacrylamide gel electrophoresis, since the adenosine analogs do not significantly affect total protein synthesis. When total protein synthesis is inhibited by incubation of the cells with cycloheximide, puromycin, or actinomycin D, chemotaxis is correspondingly inhibited. The results suggest that the continuous synthesis of one or more cellular proteins is required for chemotaxis by RAW264 cells.
D000241:Adenosine / Q000031:analogs & derivatives*; D000818:Animals; D002460:Cell Line; D002633:Chemotaxis / Q000187:drug effects*; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D007536:Isomerism; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D014176:Protein Biosynthesis / Q000187:drug effects*; D011691:Puromycin / Q000494:pharmacology; D012263:Ribonucleosides / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014372:Tubercidin / Q000494:pharmacology*
D012263:Ribonucleosides; C018258:3-deazaadenosine; D003609:Dactinomycin; D011691:Puromycin; D003513:Cycloheximide; D000241:Adenosine; D014372:Tubercidin