Alterations of Ca2+/calmodulin-dependent protein kinase II and its messenger RNA in the rat hippocampus following normo- and hypothermic ischemia.
The change in the subcellular distribution of Ca2+/calmodulin-dependent protein kinase II was studied in the rat hippocampus following normothermic and hypothermic transient cerebral ischemia of 15 min duration. A decrease in immunostaining of Ca2+/calmodulin-dependent protein kinase II was observed at 1 h of reperfusion which persisted until cell death in the CA1 region. In the CA3 and dentate gyrus areas immunostaining recovered at one to three days of reperfusion. The CA2+/calmodulin-dependent protein kinase II was translocated to synaptic junctions during ischemia and reperfusion which could be due to a persistent change in the intracellular calcium ion homeostasis. The expression of the messenger RNA of the alpha-subunit of Ca2+/calmodulin-dependent protein kinase II decreased in the entire hippocampus during reperfusion, and was most marked in the dentate gyrus at 12 h of reperfusion. This decrease could be a feedback downregulation of the mRNA due to increased Ca2+/calmodulin-dependent protein kinase II activation. Intraischemic hypothermia protected against ischemic neuronal damage and attenuated the ischemia-induced decrease of Ca2+/calmodulin-dependent protein kinase II immunostaining in all hippocampal regions. Hypothermia also reduced the translocation of Ca2+/calmodulin-dependent protein kinase II and restored Ca2+/calmodulin-dependent protein kinase II alpha messenger RNA after ischemia. The data suggest that ischemia leads to an aberrant Ca2+/calmodulin-dependent protein kinase II mediated signal transduction in the CA1 region, which is important for the development of delayed neuronal damage. Hypothermia enhances the restoration of the Ca2+/calmodulin-dependent protein kinase II mediated cell signalling.
Department of Neurobiology, Lund University Hospital, Sweden.
B R
BR
Hu
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F
Kamme
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Wieloch
D000818:Animals; D001345:Autoradiography; D002545:Brain Ischemia / Q000201:enzymology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000096:biosynthesis / Q000378:metabolism*; D015536:Down-Regulation; D004591:Electrophoresis, Polyacrylamide Gel; D006624:Hippocampus / Q000201:enzymology* / Q000648:ultrastructure; D007035:Hypothermia / Q000201:enzymology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008970:Molecular Weight; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D013347:Subcellular Fractions / Q000201:enzymology
D012333:RNA, Messenger; D017871:Calcium-Calmodulin-Dependent Protein Kinases