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.