Protein kinase C-gamma and calcium/calmodulin-dependent protein kinase II-alpha are persistently translocated to cell membranes of the rat brain during and after middle cerebral artery occlusion.
The levels of protein kinase C-gamma (PKC-gamma ) and the calcium/calmodulin-dependent kinase II-alpha (CaMKII-alpha) were measured in crude synaptosomal (P2), particulate (P3), and cytosolic (S3) fractions of the neocortex of rats exposed to 1-hour and 2-hour middle cerebral artery occlusion (MCAO) and 2-hour MCAO followed by 2-hour reperfusion. During MCAO, PKC levels increased in P2 and P3 in the most severe ischemic areas concomitantly with a decrease in S3. In the penumbra, PKCgamma decreased in S3 without any significant increases in P2 and P3. Total PKC-gamma also decreased in the penumbra but not in the ischemic core, suggesting that the protein is degraded by an energy-dependent mechanism, possibly by the 26S proteasome. The CaMKII-alpha levels increased in P2 but not P3 during ischemia and reperfusion in all ischemic regions, particularly in the ischemic core. Concomitantly, the levels in S3 decreased by 20% to 40% in the penumbra and by approximately 80% in the ischemic core. There were no changes in the total levels of CaMKII-alpha during MCAO. The authors conclude that during and after ischemia, PKC and CaMKII-alpha are translocated to the cell membranes, particularly synaptic membranes, where they may modulate cellular function, such as neurotransmission, and also affect cell survival. Drugs preventing PKC and/or CaMKII-alpha translocation may prove beneficial against ischemic cell death.
Matsumoto
Shohei
S
Laboratory for Experimental Brain Research, Wallenberg Neuroscience Center, Lund University Hospital, Lund, Sweden. shohei@tokyo-med.ac.jp
Shamloo
Mehrdad
M
Matsumoto
Eriko
E
Isshiki
Atsushi
A
Wieloch
Tadeusz
T
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000201:enzymology* / Q000473:pathology; D015153:Blotting, Western; D001923:Brain Chemistry / Q000502:physiology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000503:physiopathology; D008297:Male; D020768:Middle Cerebral Artery / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism*; D021381:Protein Transport; D051381:Rats; D017208:Rats, Wistar; D013347:Subcellular Fractions / Q000201:enzymology; D013574:Synaptosomes / Q000201:enzymology
C087857:protein kinase C gamma; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases