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Studies on the effect of mevinolin (lovastatin) and mevastatin (compactin) on the fusion of L6 myoblasts

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Abstract

The effect of mevastatin and mevinolin on the fusion of L6 myoblasts was studied. Both compounds were potent inhibitors of myoblast fusion at concentrations as low as 0.25 μM, 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 causing 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 differentiation. The presence of both compounds inhibited the incorporation of labeled mannose from GDP-mannose into lipid-sugar and N-linked glycoprotein, but the inhibition was reversed by addition of exogenous dolichol phosphate to the incorporation mixture. The main conclusion from these studies is that mevinolin and mevastatin are inhibiting myoblast fusion by affecting the synthesis of fusogenic cell surface N-linked glycoproteins probably by affecting the synthesis of dolichol phosphate containing oligosaccharides that are required as intermediates in N-linked glycoprotein biosynthesis.

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Abbreviations

HMG-CoA:

3-hydroxy-3-methylglutaryl coenzyme A

Dol:

dolichol

Dol-P:

dolichol phosphate

Man:

mannose

GlcNAc:

N-acetylglucosamine

Glc:

glucose

conA:

concanavalin A

WGA:

wheat germ agglutinin

CPK:

creatine phosphokinase

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Authors and Affiliations

  1. Department of Chemistry, University of Manitoba, R3T 2N2, Winnipeg, Manitoba, Canada

    R. S. Belo & J. C. Jamieson

  2. Department of Microbiology, University of Manitoba, R3T 2N2, Winnipeg, Manitoba, Canada

    J. A. Wright

  3. Manitoba Institute of Cell Biology, Winnipeg, Manitoba, Canada

    J. A. Wright

Authors
  1. R. S. Belo
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  2. J. C. Jamieson
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  3. J. A. Wright
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Belo, R.S., Jamieson, J.C. & Wright, J.A. Studies on the effect of mevinolin (lovastatin) and mevastatin (compactin) on the fusion of L6 myoblasts. Mol Cell Biochem 126, 159–167 (1993). https://doi.org/10.1007/BF00925694

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  • DOI: https://doi.org/10.1007/BF00925694

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