期刊
EXPERIMENTAL NEUROLOGY
卷 177, 期 2, 页码 538-546出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1006/exnr.2002.8002
关键词
endoplasmic reticulum; initiation factors; mouse brain; phosphorylation; protein synthesis; stress response; transient focal cerebral ischemia
Transient global cerebral ischemia triggers suppression of the initiation step of protein synthesis, a pro. cess which is controlled by endoplasmic reticulum (ER) function. ER function has been shown to be disturbed after transient cerebral ischemia, as indicated by an activation of the ER-resident eIF2alpha kinase PERK. In this study, we investigated ischemia-induced changes in protein levels and phosphorylation states of the initiation factors eIF2a, eIF2Bepsilon, and eIF4G1 and of p70 S6 kinase, proteins playing a central role in the control of the initiation of translation. Transient focal cerebral ischemia was induced in mice by occlusion of the left middle cerebral artery. Transient ischemia caused a long-lasting suppression of global protein synthesis. eIF2a was transiently phosphorylated after ischemia, peaking at 1-3 h of recovery. eIF2Be and p70 S6 kinase were completely dephosphorylated during ischemia and phosphorylation did not recover completely following reperfusion. In addition, eIF2Bepsilon, eIF4G1, and p70 S6 kinase protein levels decreased progressively with increasing recirculation time. Thus, several different processes contributed to ischemia-induced suppression of the initiation of protein synthesis: a long-lasting dephosphorylation of eIF2Bepsilon and p70 S6K starting during ischemia, a transient phosphorylation of eIF2a during early reperfusion, and a marked decrease of eIF2Bepsilon, eIF4G1, and p70 S6K protein levels starting during vascular occlusion (eIF4G1). Study of the mechanisms underlying ischemia-induced suppression of the initiation step of translation will help to elucidate the role of protein synthesis inhibition in the development of neuronal cell injury triggered by transient cerebral ischemia. (C) 2002 Elsevier Science (USA).
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