Transcriptional induction and translational inhibition of Arc and Cugbp2 in mice hippocampus after transient global ischemia under normothermic condition.
Mild hypothermia protects against neuronal damage after transient global ischemia in experimental animals. The exact mechanism of this protective effect remains to be elucidated. The purpose of the present study was to investigate the molecular mechanisms relevant to different neurologic responses to hypothermia and normothermia. Transient global ischemia was induced in C57BL/6 mice by bilateral common carotid artery occlusion for 10 min. Hypothermia provided robust neuroprotection in the hippocampus region and dramatically reduced the mortality rate. Using adaptor-tagged competitive polymerase chain reaction, we obtained the relative transcription levels of 1210 genes in the hippocampal region and compared the expression patterns of these genes. Two genes, Activity-regulated cytoskeleton-associated protein (Arc) and CUG-binding protein-2 (Cugbp2), showed remarkable and persistent increases in their expression levels in normothermic mice, compared with in both sham and hypothermic mice. Despite the increased transcription of Arc and Cugbp2, an immunohistochemistry analysis did not show comparable increases in the translations of both genes. Only a transient increase in Arc protein was observed in the granule cells of the dentate gyrus at 6 h after reperfusion. A remarkable decrease in Cugbp2 protein was observed in the pyramidal cells of the hippocampal CA1-CA3, in accordance with the progress of neuronal degeneration. A decrease in Cugbp2 protein was not observed in hypothermic mice. These results suggest that transient global ischemia induces the translational inhibition of genes with increased expression not in hypothermic, but in normothermic mice. Thus, translational inhibition might play an important role in the progress of neuronal injury after transient global ischemia.
Otsuka
Noboru
N
Laboratory of Molecular Pharmacology, Division of Pharmaceutical Sciences, Kanazawa University Graduate School of Natural Science and Technology, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan. noboru.otsuka@po.rd.taisho.co.jp
Tsuritani
Katsuki
K
Sakurai
Takanobu
T
Kato
Kikuya
K
Matoba
Ryo
R
Itoh
Jiro
J
Okuyama
Shigeru
S
Yamada
Kiyofumi
K
Yoneda
Yukio
Y
D000818:Animals; D001831:Body Temperature / Q000235:genetics; D000067878:CELF Proteins; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D014176:Protein Biosynthesis / Q000235:genetics; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics*
D000067878:CELF Proteins; C117363:CELF2 protein, human; D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C092069:activity regulated cytoskeletal-associated protein