Time course of the translocation and inhibition of protein kinase C during complete cerebral ischemia in the rat.
The time course for the ischemia-induced changes in the subcellular distribution of protein kinase C (PKC) (alpha), (beta II), and (gamma) and the activity of PKC were studied in the neocortex of rats subjected to 1, 2, 3, 5, 10, and 15 min of global cerebral ischemia. In the particulate fraction, a 14-fold increase in PKC (gamma) levels was seen at 3 min of ischemia, which further increased at 5-15 min of ischemia. At 15 min of ischemia, PKC (alpha) and (beta II) levels had increased two- and six-fold, respectively. In the cytosolic fraction, a transient early 1.4-fold increase in PKC (beta II) and PKC (gamma) levels was seen, whereas no change in the levels PKC (alpha) was noted. PKC (gamma) levels then progressively declined, reaching 50% at 15 min of ischemia. At 5 min of ischemia, a 43% decrease in PKC activity was seen in the particulate fraction, reaching 50% at 15 min of ischemia concomitant with a 27% decrease in the cytosolic fraction. There was no change in the activator-independent PKC activity. Pretreatment with the ganglioside AGF2 prevented the redistribution of PKC (gamma) in the particulate fraction at 5 min, but not at 10 min of ischemia. The observed time course for the translocation of PKC (gamma) parallels the ischemia-induced release of neurotransmitters and increased levels of diacylglycerols, arachidonate, and increased levels of diacylglycerols, arachidonate, and intracellular calcium and delineates this subspecies as especially ischemia-sensitive. Ganglioside pretreatment delayed the translocation of PKC (gamma), possibly by counter-acting the effects of ischemia-induced factors that favor PKC binding to cell membranes.
Department of Neurobiology, Experimental Research Center, University Hospital, Lund, Sweden.
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Cardell
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Wieloch
D000818:Animals; D001692:Biological Transport; D002545:Brain Ischemia / Q000201:enzymology*; D005677:G(M1) Ganglioside / Q000031:analogs & derivatives / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013347:Subcellular Fractions / Q000201:enzymology; D013997:Time Factors
D007527:Isoenzymes; D005677:G(M1) Ganglioside; C051355:siagoside; D011493:Protein Kinase C