STUDIES ON THE EFFECT OF MEVINOLIN (LOVASTATIN) AND MEVASTATIN (COMPACTIN) ON THE FUSION OF L6 MYOBLASTS

The effect of mevastatin and mevinolin on the fusion of L6 myoblasts w as studied. Both compounds were potent inhibitors of myoblast fusion a t concentrations as low as 0.25 mu M, but fusion was restored when the inhibitors were removed. Both compounds resulted in decreased binding of conA and WGA to cell surface oligosaccharides showing they were ca using a reduction in N-linked cell surface glycoproteins. There was a reduction in creatine phosphokinase activities in the presence of both compounds showing that they were affecting biochemical differentiatio n. The presence of both compounds inhibited the incorporation of label ed mannose from GDP-mannose into lipid-sugar and N-linked glycoprotein , but the inhibition was reversed by addition of exogenous dolichol ph osphate to the incorporation mixture. The main conclusion from these s tudies is that mevinolin and mevastatin are inhibiting myoblast fusion by affecting the synthesis of fusogenic cell surface N-linked glycopr oteins probably by affecting the synthesis of dolichol phosphate conta ining oligosaccharides that are required as intermediates in N-linked glycoprotein biosynthesis.