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Gangliosides Prevent Ischemia‐Induced Down‐Regulation of Protein Kinase C in Fetal Rat Brain
Author(s) -
Magal Ella,
Louis JeanClaude,
And Jose Aguilera.,
Yavin Ephraim
Publication year - 1990
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1990.tb05805.x
Subject(s) - protein kinase c , medicine , endocrinology , ischemia , cytosol , fetus , protein kinase a , intraperitoneal injection , gestation , chemistry , kinase , biology , biochemistry , enzyme , pregnancy , genetics
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 ∼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 Ca 2+ ‐phosphatidylserinc‐indepcndent 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.