Ischemic pre-conditioning affects the subcellular distribution of protein kinase C and calcium/calmodulin-dependent protein kinase II in the gerbil hippocampal CA1 neurons.
Brief ischemic episode, which in itself is not lethal, confers tolerance to subsequent ischemic insults. Since intracellular signal transduction system has been implicated in ischemic cell death, we studied the effect of pre-conditioning on the changes in the subcellular distribution of protein kinase Cgamma (PKCgamma) as well as CaM kinase II (CaMKII). Gerbils were pre-conditioned by a sublethal 2 min cerebral ischemia 24 h prior to lethal 5 min ischemia. The pre-conditioning generally downregulated PKCgamma and CaMKII in the CA1 hippocampus. Especially at the starting point of the second lethal ischemia, the cytosolic PKCgamma level was about 40% lower in the pre-conditioned group. Also, the crude synaptosomal CaMKII level at 24 h reperfusion following the second ischemia was significantly lower in the pre-conditioned group, showing enhanced recovery of CaMKII translocation. Present results suggest that ischemic pre-conditioning may downregulate calcium-mediated cell signaling system, enhancing normalization of calcium homeostasis, perturbed by the second ischemia of lethal duration.
Katsura
K I
KI
The Second Department of Internal Medicine, Nippon Medical School, Tokyo, Japan. k-katsur@nms.ac.jp
Kurihara
J
J
Kato
H
H
Katayama
Y
Y
D000818:Animals; D002545:Brain Ischemia / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002451:Cell Compartmentation / Q000502:physiology*; D016923:Cell Death / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology; D005849:Gerbillinae; D006624:Hippocampus / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D015151:Immunoblotting; D019194:Ischemic Preconditioning; D008297:Male; D009474:Neurons / Q000201:enzymology* / Q000473:pathology; D011493:Protein Kinase C / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013574:Synaptosomes / Q000378:metabolism
D011493:Protein Kinase C; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases