Biologia, Bratislava 54/Suppl. 6: 41-45, 1999.
ISSN 0006-3088 (Biologia). ISSN 1335-6399 (Biologia. Section Cellular and Molecular Biology).
Possible mechanisms of protein synthesis inhibition in CNS during postischemic reperfusion.
Jozef Burda1*, Miroslava Nemethova1, Cristina Martin De La Vega2, Alberto Alcazar2, Juan L. Fando3 & Matilde Salinas2
1 Institute of Neurobiology, Slovak Academy of Sciences, Soltesovej 4, SK-04001 Kosice, Slovakia; fax: ++421 95 765074, e-mail: email@example.com
2 Servicio de Bioquimica, Departamento de Investigacon, Hospital Ramon y Cajal, 28034, Madrid, Spain
3 Departamento de Bioquimica y Biologia Molecular, Universidad de Alcala, Alcala de Henares, 28871 Madrid, Spain
* corresponding author
Received: January 5, 1999 / Accepted: October 5, 1999
Alterations in protein synthesis during ischemia and subsequent reperfusion may be evaluated in terms of the capacity for protein synthesis or the integrity of the protein synthesising machinery, namely the ribosomes, initiation and elongation factors. Although ischemia per se produces relatively moderate changes which are dependent on the model and duration of the ischemia and intraischemic temperature, generates background for profound protein synthesis alterations occurring during subsequent reperfusion. First minutes of postischemic reperfusion are characterised by a nearly complete block of translation, focused on the inhibition of initiation, which is manifested by the disaggregation of polyribosomes to monosomes and ribosomal subunits. This acute inhibition of protein synthesis, which can be seen in all regions of CNS, seems to be caused by a phosphorylation of a-subunit of initiation factor 2 (eIF-2a) and a decreased activity of initiation factor 2B (eIF-2B). After the common transient inhibition of initiation, most brain regions recover their protein synthesis capability. However, inhibition in selectively vulnerable regions is persistent. The persistent inhibition of translation in selective vulnerable brain regions is presumably caused by an inhibition of ternary complex formation which could be partly independent on the phosphorylation status of eIF2a. Moreover, the massive release of glutamate, responsible for an increase in cytosolic Ca+2, which is able to originate phosphorylation of eukaryotic elongation factor 2 (eEF-2) by a Ca+2/calmoduline-dependent enzyme eEF-2 kinase, could be involved simultaneously in this process.
Key words: transient cerebral ischemia, reperfusion, translation, protein synthesis, initiation factors.