The myelin-associated glycoprotein inhibitor BENZ induces outgrowth and survival of rat dorsal root ganglion cell cultures.
The novel myelin-associated glycoprotein (MAG) inhibitor BENZ binds to the N-acetylneuraminic acid (Neu5Ac) portion of the N-terminal Ig-like domain of MAG. Treatment of rat dorsal root ganglion (DRG) cell cultures with BENZ-induced outgrowth of neurofilament 200-positive neurites improved survival of neurons and increased the number of GFAP-positive cells, as determined by fluorescence and confocal laser microscopy and by Western immunoblotting. Furthermore, treatment of DRG cell cultures with BENZ repressed gene and protein expression of the small GTPase RhoA but induced expression of Rho GTP-activating proteins 5 and 24, likely to counteract protein kinase A activity. Specifically, expression of inhibitors of neurite outgrowth, for example, Rock2 and PAK4, was repressed, but cofilin 1, a promoter of axonal growth, was induced. We propose that the MAG inhibitor BENZ abrogates the RhoA-ROCK-cofilin pathway to promote neurite outgrowth. Our findings require confirmation by in vivo animal studies.
Nowicki
Marcin
M
University of Leipzig, Institute of Anatomy, Leipzig, Germany.
Kosacka
Joanna
J
Brossmer
Reinhard
R
Spanel-Borowski
Katharina
K
Borlak
Jürgen
J
D000818:Animals; D000831:Animals, Newborn; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000166:cytology*; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D046228:Microarray Analysis / Q000379:methods; D008954:Models, Biological; D018992:Myelin-Associated Glycoprotein / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019158:N-Acetylneuraminic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016501:Neurites / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000648:ultrastructure*; D051381:Rats; D013997:Time Factors
D018992:Myelin-Associated Glycoprotein; D009419:Nerve Tissue Proteins; D019158:N-Acetylneuraminic Acid