Isoforms of protein kinase C in postsynaptic densities after cerebral ischemia.
Relatively mild ischemic insult can lead to delayed neuronal cell death in vulnerable brain regions. We provide evidence that the protein composition of the postsynaptic densities (PSD) undergoes rapid modification after 15 min postdecapitative as well as 5 min transient global ischemia. We observed a significant increase in cPKC and nPKC protein content in the postischemic PSD. Of the calcium-regulated PKC isoforms, the alpha and beta subtypes increase in PSD over ten times above the control values whereas gamma PKC, an isoform most abundant in the native PSD structure, shows relatively smaller changes under ischemic conditions. For the first time, the PSD membrane translocation of Ca(2+)-independent isoforms delta and epsilon is shown. The yield of the PSD protein preparation from the postischemic cortex was two times higher compared with control. This correlated with an abundant increase in electron density and changes in ultrastructure of PSD isolated from postischemic cortex. Also sections from CA1 gerbils hippocampus after transient ischemia showed persistent enlargement of postsynaptic densities up to 24 h of reperfusion. This was accompanied by elevation of the PSD/cytoskeleton-associated alpha, beta PKC immunoreactivity and other changes in neuronal and glial cell morphology typical of the early postischemic degeneration. Sustained changes in PKC composition and organization of postsynaptic membranes during and after ischemia may cause persistent alteration in synaptic transmission and subsequently contribute to delayed neuronal injury.
Zablocka
B
B
Laboratory of Molecular Neuropathology, Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland. zablocka@cmdik.pan.pl
Gajkowska
B
B
Czechmańska
T
T
Domańska-Janik
K
K
D000818:Animals; D015153:Blotting, Western; D002545:Brain Ischemia / Q000201:enzymology* / Q000473:pathology; D003720:Densitometry; D004591:Electrophoresis, Polyacrylamide Gel; D005849:Gerbillinae; D015151:Immunoblotting; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008854:Microscopy, Electron; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013347:Subcellular Fractions / Q000201:enzymology; D013569:Synapses / Q000201:enzymology* / Q000473:pathology
D007527:Isoenzymes; D009419:Nerve Tissue Proteins; D011493:Protein Kinase C