Decreased GAP-43 accumulation in neurite tips of cultured hippocampal neurons by acrylamide.
The critical axonopathy- producing effect of acrylamide (ACR) is hypothesized to be an interruption of fast vesicular transport resulting in a deficiency of distal axonal proteins. This study used the accumulation of growth associated protein- 43 (GAP-43) in neurite tips of cultured hippocampal neurons as a model to examine the effect of an ACR block of fast transport on the eventual protein concentration within the distal axon. Twenty-four hour incubation with ACR produced a dose-dependent reduction with 0.5mM and 1.0mM concentrations in the percent of neurites with a terminal GAP-43 accumulation. No change in cell size (area), cell body GAP-43 fluorescence, distal neurite fluorescence, absolute tip fluorescence or neurite length were observed. Another known inhibitor of transport, colchicine (COL) also caused a significant decrease in the percent of neurites with a GAP-43 accumulation; propionamide (PA), a non-neurotoxic analogue of ACR, had no effect on protein accumulation. These findings support the hypothesis that the disruption of fast transport by ACR can lead to depletion of vital proteins in the distal axon.
Clarke
C H
CH
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, USA.
Sickles
D W
DW
D020106:Acrylamide; D000178:Acrylamides / Q000494:pharmacology*; D000577:Amides / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D003078:Colchicine / Q000494:pharmacology; D019922:GAP-43 Protein; D006133:Growth Substances / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats
D000178:Acrylamides; D000577:Amides; D019922:GAP-43 Protein; D006133:Growth Substances; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D020106:Acrylamide; C034666:propionamide; D003078:Colchicine