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Cerebral ischemia leads to a massive increase in cytoplasmic calcium activity resulting from an influx of calcium ions into cells and a release of calcium from mitochondria and endoplasmic reticulum (ER). It is widely believed that this increase in cytoplasmic calcium activity plays a major role in ischemic cell injury in neurons. Recently, this concept was(More)
In the physiological state, there appears to be a regulatory link between endoplasmic reticulum (ER) Ca(2+) homoeostasis and the initiation of neuronal protein synthesis. Exposing neuronal cell cultures to thapsigargin (Tg), an irreversible inhibitor of sarcoplasmic/ER Ca(2+)-ATPase (SERCA), induced an almost complete suppression of protein synthesis, which(More)
Changes in neuronal calcium activity in the various subcellular compartments have divergent effects on affected cells. In the cytoplasm and mitochondria, where calcium activity is normally low, a prolonged excessive rise in free calcium levels is believed to be toxic, in the endoplasmic reticulum (ER), in contrast, calcium activity is relatively high and(More)
The endoplasmic reticulum (ER) is a subcellular compartment playing a central role in calcium storage and signaling. Disturbances of ER calcium homeostasis constitute a severe form of stress interfering with central functions of this structure including the folding and processing of newly synthesized membrane and secretory proteins. Blocking the folding and(More)
A new group of proteins, small ubiquitin-like modifier (SUMO) proteins, has recently been identified and protein sumoylation has been shown to play a major role in various signal transduction pathways. Here, we report that transient global cerebral ischemia induces a marked increase in protein sumoylation. Mice were subjected to 10 mins severe forebrain(More)
Various physiological, biochemical and molecular biological disturbances have been put forward as mediators of neuronal cell injury in acute and chronic pathological states of the brain such as ischemia, epileptic seizures and Alzheimer's or Parkinson's disease. These include over-activation of glutamate receptors, a rise in cytoplasmic calcium activity and(More)
Mice were subjected to 60 min occlusion of the left middle cerebral artery (MCA) followed by 1-6 h of reperfusion. Tissue samples were taken from the MCA territory of both hemispheres to analyse ischaemia-induced changes in the phosphorylation of the initiation factor eIF-2alpha, the elongation factor eEF-2 and p70 S6 kinase by western blot analysis. Tissue(More)
  • Wulf Paschen
  • Journal of cerebral blood flow and metabolism…
  • 2003
Shutdown of translation is a highly conserved response of cells to a severe form of metabolic, thermal, or physical stress. After the metabolic stress induced by transient cerebral ischemia, translational recovery is observed only in cells that withstand the transient interruption of blood supply, implying that restoration of translation critically(More)
Biosynthesis of the polyamines spermidine and spermine and their precursor putrescine is controlled by the activity of the two key enzymes ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMDC). In the adult brain, polyamine synthesis is activated by a variety of physiological and pathological stimuli, resulting most prominently in an(More)
This study was designed to investigate whether small ubiquitin-like modifier (SUMO) conjugation is activated after focal cerebral ischemia. Transient ischemia induced a dramatic increase in SUMO2/3 protein conjugates. The most pronounced changes were found in the parietal cortex. SUMO2/3 conjugation was particularly high in neurons located at the border of(More)