Activation of p38 kinase in the gerbil hippocampus showing ischemic tolerance.
Ischemic tolerance is a phenomenon in which brief episodes of ischemia protect against the lethal effects of subsequent periods of prolonged ischemia. The authors investigated the activation of p38 mitogen-activated protein kinase (p38) in the gerbil hippocampus by Western blotting and immunohistochemistry to clarify the role of p38 kinase in ischemic tolerance. After the 2-minute global ischemia, immunoreactivity indicating active p38 was enhanced at 6 hours of reperfusion and continuously demonstrated 72 hours after ischemia in CA1 and CA3 neurons. Pretreatment with SB203580, an inhibitor of active p38 (0-30 micromol/l), 30 minutes before the 2-minute ischemia reduced the ischemic tolerance effect in a dose-dependent manner. Immunoblot analysis indicated that alteration of the phosphorylation pattern of p38 kinase in the hippocampus after subsequent lethal ischemia was induced by the preconditioning. These findings suggest that lasting activation of p38 may contribute to ischemic tolerance in CA1 neurons of the hippocampus and that components of the p38 cascade can be target molecules to modify neuronal survival after ischemia.
Nishimura
Masaki
M
Department of Neurosurgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Sugino
Toshiyuki
T
Nozaki
Kazuhiko
K
Takagi
Yasushi
Y
Hattori
Itaro
I
Hayashi
Junya
J
Hashimoto
Nobuo
N
Moriguchi
Tetsuo
T
Nishida
Eisuke
E
D000818:Animals; D002545:Brain Ischemia / Q000201:enzymology* / Q000473:pathology*; D002470:Cell Survival; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005849:Gerbillinae; D006624:Hippocampus / Q000201:enzymology* / Q000473:pathology; D007093:Imidazoles / Q000494:pharmacology; D020287:In Situ Nick-End Labeling; D019194:Ischemic Preconditioning; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases
D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580