Induction of protein kinase Cdelta subspecies in neurons and microglia after transient global brain ischemia.
The delayed death of CA1 neurons after global brain ischemia is associated with induction of apoptosis genes and is inhibited by protein synthesis inhibitors, suggesting that the degeneration of CA1 pyramidal neurons is an active process that requires new gene expression. The transient global ischemia model has been extensively used to identify enzymes and other proteins underlying delayed neuronal cell death. The expression of protein kinase C (PKC) subspecies after 20 minutes of global brain ischemia produced by a four-vessel occlusion model in the rat was studied. From the multiple PKC subspecies studied, only PKCdelta mRNA was significantly up-regulated in CA1 pyramidal neurons at 24 hours and in activated microglia at 3 to at least 7 days after ischemia. The induction of PKCdelta mRNA was also found in the cortex at 8 hours and 3 days after ischemia. This cortical but not hippocampal induction was regulated by an alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid/kainate receptor antagonist, 6-nitro-7-sulfamobenzo[f]quinoxaline-2,3-dione, and glucocorticoids. An N-methyl-D-aspartate receptor antagonist, MK-801, was without effect on the induction of PKCdelta subspecies. The selective and prolonged induction of the PKCdelta mRNA and protein first in CA1 pyramidal neurons and at a later stage in activated microglia suggests that the PKCdelta isozyme may take part in regulation of the delayed death of CA1 neurons after transient global brain ischemia.
Koponen
S
S
A. I. Virtanen Institute for Molecular Sciences, University of Kuopio, Finland.
Goldsteins
G
G
Keinänen
R
R
Koistinaho
J
J
D000818:Animals; D015151:Immunoblotting; D007150:Immunohistochemistry; D002546:Ischemic Attack, Transient / Q000201:enzymology*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008297:Male; D017628:Microglia / Q000201:enzymology*; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D051745:Protein Kinase C-delta; D017966:Pyramidal Cells / Q000201:enzymology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D007527:Isoenzymes; D012333:RNA, Messenger; C497260:Prkcd protein, rat; D011493:Protein Kinase C; D051745:Protein Kinase C-delta