GT1b ganglioside prevents tetanus toxin-induced protein kinase C activation and down-regulation in the neonatal brain in vivo.
A single dose of 0.25 ng of tetanus toxin (TeTx), equivalent to approximately 5 minimal lethal doses, injected intracerebrally to 1-day-old rats, caused translocation, i.e., activation, of Ca(2+)-phosphatidylserine-dependent protein kinase C (PKC) from the cytosolic to the membrane compartment within 1 h. Six hours after treatment with the toxin, a 40-50% reduction in the total brain PKC (cytosolic plus membrane) activity was noticed. GT1b (2 micrograms per brain) ganglioside, a putative receptor for TeTx, completely prevented enzyme translocation when injected intracerebrally 30 min before toxin administration and abolished down-regulation after 6 h from the time of toxin injection. GM1 (2 micrograms per brain), a ganglioside of lesser affinity for TeTx, produced by itself a 20-30% reduction of the total PKC activity and did not reverse TeTx-induced PKC down-regulation after 6 h. 12-O-Tetradecanoylphorbol 13-acetate (TPA) phorbol ester, administered at a concentration of 5 x 10(-5) M, caused activation and down-regulation of the enzyme, although with several orders of magnitude lesser potency. GT1b prevented the TPA-induced down-regulation.
Aguilera
J
J
Department de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Cerdanyola, Spain.
Padrós-Giralt
C
C
Habig
W H
WH
Yavin
E
E
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D002240:Carbohydrate Sequence; D004789:Enzyme Activation / Q000187:drug effects; D005677:G(M1) Ganglioside / Q000494:pharmacology; D005732:Gangliosides / Q000494:pharmacology*; D007700:Kinetics; D008969:Molecular Sequence Data; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D013744:Tetanus Toxin / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
D005732:Gangliosides; D013744:Tetanus Toxin; D005677:G(M1) Ganglioside; C016481:trisialoganglioside GT1; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate