Ischemia-induced inhibition of the initiation factor 2α phosphatase activity in the rat brain

被引:23
作者
de la Vega, CM
Burda, J
Salinas, M
机构
[1] Hosp Ramon & Cajal, Dept Invest, Serv Bioquim, E-28034 Madrid, Spain
[2] Slovak Acad Sci, Inst Neurobiol, Kosice 04001, Slovakia
关键词
eIF2 alpha kinases; initiation factor 2; protein phosphatase 1 alpha and 2A; transient cerebral ischemia; translation;
D O I
10.1097/00001756-200104170-00031
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Rats were subjected to the standard four-vessel occlusion model of brain transient ischemia for 30 min. Following different recirculation periods, the level of phosphorylation of the initiation factor 2 subunit alpha (eIF2 alpha) and the eIF2 alpha kinase/s and phosphatase/s activity were determined. eIF2 alpha phosphorylation significantly increased very early during reperfusion (10-30 min), recovering at 4 h of reperfusion. Activation of any eIF2 alpha kinases studied during ischemia or reperfusion was not noted. Conversely, eIF2 alpha phosphatase activity significantly decreased at 10-15 min of reperfusion, reaching values even higher than in controls at 2-4 h of reperfusion. Our results support the hypothesis that the reperfusion-induced phosphorylated eIF2 alpha changes are at least a result of the transiently eIF2 alpha phosphatase inhibition. NeuroReport 12:1021-1025 (C) 2001 Lippincott Williams & Wilkins.
引用
收藏
页码:1021 / 1025
页数:5
相关论文
共 24 条
[1]  
Alcazar A, 1997, J NEUROCHEM, V69, P1703
[2]   Type 1 phosphatase inhibitors reduce the restoration of guanine nucleotide exchange activity of eukaryotic initiation factor 2B in inhibited reticulocyte lysates rescued by hemin [J].
Babu, SVN ;
Ramaiah, KVA .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1996, 327 (02) :201-208
[3]   Characterization of the hemin-sensitive eukaryotic initiation factor 2α kinase from mouse nonerythroid cells [J].
Berlanga, JJ ;
Herrero, S ;
de Haro, C .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (48) :32340-32346
[4]   Characterization of a mammalian homolog of the GCN2 eukaryotic initiation factor 2α kinase [J].
Berlanga, JJ ;
Santoyo, J ;
de Haro, C .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1999, 265 (02) :754-762
[5]  
BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
[6]   PHOSPHORYLATION OF THE ALPHA-SUBUNIT OF INITIATION-FACTOR 2 CORRELATES WITH THE INHIBITION OF TRANSLATION FOLLOWING TRANSIENT CEREBRAL-ISCHEMIA IN THE RAT [J].
BURDA, J ;
MARTIN, ME ;
GARCIA, A ;
ALCAZAR, A ;
FANDO, JL ;
SALINAS, M .
BIOCHEMICAL JOURNAL, 1994, 302 :335-338
[7]   Cellular mechanisms regulating protein phosphatase-1 - A key functional interaction between inhibitor-2 and the type 1 protein phosphatase catalytic subunit [J].
Connor, JH ;
Frederick, D ;
Huang, HB ;
Yang, J ;
Helps, NR ;
Cohen, PTW ;
Nairn, AC ;
DePaoli-Roach, A ;
Tatchell, K ;
Shenolikar, S .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (25) :18670-18675
[8]  
CROUCH D, 1984, J BIOL CHEM, V259, P363
[9]   MAPs and POEP of the roads from prokaryotic to eukaryotic kingdoms [J].
Datta, B .
BIOCHIMIE, 2000, 82 (02) :95-107
[10]   Resistance of initiation factor 2 (eIF-2α) kinases to staurosporine:: An approach for assaying the kinases in crude extracts [J].
de la Vega, CM ;
García, A ;
Martín, ME ;
Alcázar, A ;
Marin, O ;
Quevedo, C ;
Salinas, M .
CELLULAR SIGNALLING, 1999, 11 (06) :399-404