Inhibition of nerve growth factor-induced B-50/GAP-43 expression by antisense oligomers interferes with neurite outgrowth of PC12 cells.
Substantial evidence has now been gathered for the involvement of B-50/GAP-43 in neuronal development and regeneration. The precise role of this protein, however, is still debated. In an earlier study, a linear correlation between NGF-induced neurite outgrowth and B-50/GAP-43 levels was observed in PC12 cells. To establish the involvement of B-50/GAP-43 expression in neurite outgrowth in these cells, we interfered with the expression by antisense oligomers and measured the outgrowth. In the present study, a B-50/GAP-43 antisense 5'-oligomer interfered both with the NGF-induced increase in B-50/GAP-43 and with neurite outgrowth, whereas an antisense 3'-oligomer was ineffective. We conclude, that in PC12 cells under normal conditions B-50/GAP-43 expression and neurite outgrowth are or become coupled upon NGF-induction, in contrast to the situation in PC12 clones with no or very low B-50/GAP-43 expression.
Jap Tjoen San
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Division of Molecular Neurobiology, Rudolf Magnus Institute, University Utrecht, The Netherlands.
Schmidt-Michels
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Oestreicher
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Gispen
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Schotman
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D000818:Animals; D001483:Base Sequence; D019922:GAP-43 Protein; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D016501:Neurites / Q000502:physiology* / Q000648:ultrastructure; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D016716:PC12 Cells; D051381:Rats
D019922:GAP-43 Protein; D008562:Membrane Glycoproteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D016376:Oligonucleotides, Antisense