Correlation between inhibition of myelin basic protein (arginine) methyltransferase by sinefungin and lack of compact myelin formation in cultures of cerebral cells from embryonic mice.
Sinefungin, a known inhibitor of protein methylation, inhibited the myelin basic protein (arginine) methyltransferase activity in homogenates of cultured cerebral cells from embryonic mice. Fifty percent inhibition was achieved with 25 microM sinefungin. Electron microscopic examination of the myelin fraction, isolated by gradient density centrifugation and obtained from untreated cells, revealed numerous ringlike multilamellar membranous substructures that had a major dense line periodicity, compactness, and the general appearance expected of myelin obtained by the same technique from whole brain. Cells treated with 30 microM sinefungin, which inhibits myelin basic protein methyltransferase in broken cell preparations about 60%, produced ringlike structures that were devoid of multilamellar periodicity and compactness reminiscent of the vacuolated myelin observed in subacute combined degeneration and in nitrous-oxide- or cycloleucine-treated animals in which methyltransferase activity is also inhibited. The sinefungin-induced change in multilamellar periodicity cannot be attributed to a lack of myelin basic protein, since the ratio of myelin basic protein to total protein did not decrease in sinefungin-treated cells. This primary culture system should be useful for further evaluating the hypothesis that the methylation of myelin basic protein is related to the formation of compact myelin.
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D001923:Brain Chemistry / Q000187:drug effects; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D008780:Methyltransferases / Q000037:antagonists & inhibitors; D051379:Mice; D009185:Myelin Proteins / Q000032:analysis; D009186:Myelin Sheath / Q000187:drug effects*; D011496:Protein Methyltransferases / Q000037:antagonists & inhibitors*; D011484:Protein-Arginine N-Methyltransferases / Q000037:antagonists & inhibitors*
D009185:Myelin Proteins; D000076983:Histone Methyltransferases; D008780:Methyltransferases; D011496:Protein Methyltransferases; D011484:Protein-Arginine N-Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D000241:Adenosine; C006235:sinefungin