Gangliosides prevent ischemia-induced down-regulation of protein kinase C in fetal rat brain.
Complete obstruction of the maternal blood flow to fetal rats at 20 days of gestation for a period of 10 min causes a significant shift of approximately 22% in protein kinase C (PKC) activity from a cytosolic to a membrane-bound form in the fetal brain. This translocation can be entirely reversed without losses in activity by a single intraperitoneal injection into the gravid rat of either a mixture of disialo- and trisialoganglioside [polysialoganglioside (PSG)] or by GM1 (50 mg/kg of body weight) given 3 h before onset of the ischemic episode. Cessation of blood flow for 15 min followed by a reperfusion period of 24 h results in a 47% loss in total PKC activity. This down-regulation can be almost entirely prevented upon intraperitoneal administration of GM1 3 h before, but also during and even 90 min after the onset of ischemia. The PSG mixture is also effective, particularly when given 3 h before the insult. Down-regulation of PKC is accompanied by an increase in a Ca2(+)-phosphatidylserine-independent kinase [protein kinase M (PKM)] activity, which rises from 30 pmol/min/mg of protein in control animals to a maximal value of 83.1 pmol/min/mg of protein after 15 min of ischemia and 6 h of reperfusion. By 24 h, PKM activity is 46.8 pmol/min/mg of protein. Administration of GM1 blocks completely the appearance of PKM, a result suggesting that PKC down-regulation and PKM activity elevation are intimately associated events and that both are regulated by GM1 ganglioside.
Magal
E
E
Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
Louis
J C
JC
Aguilera
J
J
Yavin
E
E
D000818:Animals; D001921:Brain / Q000196:embryology / Q000201:enzymology*; D002545:Brain Ischemia / Q000201:enzymology*; D015536:Down-Regulation; D005677:G(M1) Ganglioside / Q000494:pharmacology; D005732:Gangliosides / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats
D005732:Gangliosides; D005677:G(M1) Ganglioside; C016481:trisialoganglioside GT1; D011493:Protein Kinase C