Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuronal protein synthesis is severely depressed following stress such as heat-shock, hypoxia, and hypoglycemia. Following reversible cerebral ischemia, protein synthesis is transiently inhibited in ischemia-resistant areas, but persistently depressed in vulnerable brain regions. Eukaryotic initiation factor 2 (eIF-2) activity, that is, the formation of the ternary complex eIF-2.GTP.initiator 35S-Met-tRNA, a rate-limiting step in the initiation of cellular protein synthesis, was studied in the rat brain during and following 15 min of transient global cerebral ischemia. At 30 min and 1 hr of reperfusion, a general decrease of eIF-2 activity by approximately 50% was seen in the postmitochondrial supernatant (PMS). In the relatively resistant neocortex and CA3 region of the hippocampus, the eIF-2 activity returns to control levels at 6 hr of reperfusion, but remains depressed in the vulnerable striatum and the CA1 region. Similarly, the activity of the guanine nucleotide exchange factor (GEF), which catalyzes the exchange of GTP for GDP bound to eIF-2, a crucial step for the continued formation of the ternary complex, is transiently reduced in neocortex but persistently depressed in striatum. The postischemic decrease in eIF-2 activity is further attenuated by agarose-bound alkaline phosphatase, and mixing experiments revealed that a vanadate-sensitive phosphatase may be responsible for the depression. Addition of partially purified GEF to PMS from postischemic neocortex restored eIF-2 activity to control levels. We conclude that ischemia alters the balance between phosphorylation and dephosphorylation reactions, leading to an inhibition of GEF and a depression of ternary complex formation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Stress-induced inhibition of protein synthesis initiation: modulation of initiation factor 2 and guanine nucleotide exchange factor activities following transient cerebral ischemia in the rat. 847 77

Aminoacyl-tRNA syntheses (AARS) can catalyze the adenosine triphosphate (ATP)-dependent acylation of their cognate tRNA(s) with a specific amino acid. They can be seen as an index to reflect the energy metabolic rate of ischemic brain cells in ischemic penumbra. This study examined the relationship between arginyl-tRNA synthetase (ArgRS), one of the AARS, and cerebral ischemia in rats. The model of middle cerebral artery occlusion (MCAO) was established in rats. The expression levels of ArgRS protein and mRNA were detected in rat brain tissues at different time points following MCAO by Western blotting and RT-PCR, respectively. The results showed that the MCAO model was successfully established. Western blotting and RT-PCR analysis revealed that the ArgRS protein and mRNA were expressed in brain cells in both ischemic and normal penumbra tissues. The expression levels of ArgRS protein and mRNA peaked at 6 h after MCAO and decreased gradually. At 24 h, the expression levels of ArgRs protein and mRNA in ischemic penumbral tissues were lower than those in normal tissues. The expression levels of ArgRS mRNA and protein in ischemic penumbra varied with ischemic time, suggesting that the energy metabolism of brain cells in penumbra changed dynamically after ischemia to ensure the endogenous self-protection of the body. The brain oxygen supply should be improved as soon as possible, especially within 6-12 h after ischemia, so as to meet the demand for energy metabolism in ischemic penumbra and make sure the cell structure remains stable.
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PMID:Expression of arginyl-tRNA synthetase in rats with focal cerebral ischemia. 2471 Sep 27

tiRNAs are small non-coding RNAs generated by angiogenin-mediated tRNA cleavage during cellular stress. Some tiRNAs were shown to be cytoprotective, while other reports indicate that the generation of tiRNAs is cytotoxic. We used rat model of focal cerebral ischemia-reperfusion (I/R) injury to study the generation and regulation of tiRNAs following in vivo I/R and the impact of neuroprotective therapy on their generation. tiRNAs were induced after I/R and Minocycline therapy reduced global tiRNA levels. Our results showed that tRNA cleavage is tRNA species specific, and neuroprotective treatment does not affect all tiRNA species. We also evaluated the temporal changes in several tRNA modifying enzymes and showed a correlation between their expression and tRNA cleavage. In conclusion, we show that tiRNAs can serve as biomarkers for stroke and stroke therapy, further adding them to the repertoire of tools that can be used to monitor and treat stroke.
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PMID:Stress Induced tRNA Halves (tiRNAs) as Biomarkers for Stroke and Stroke Therapy; Pre-clinical Study. 3220 75

The gerbil is a well-known model for studying cerebral ischemia. The CA1 of the hippocampus is vulnerable to 5 min of ischemia, while the CA2-4 and dentate gyrus (DG) are resistant to it. Short-lasting ischemia, a model of transient ischemic attacks in men, results in CA1 neuron death within 2-4 days of reperfusion. Untargeted metabolomics, using LC-QTOF-MS, was used to enrich the knowledge about intrinsic vulnerability and resistance of hippocampal regions and their early post-ischemic response (IR). In total, 30 significant metabolites were detected. In controls, taurine was significantly lower and guanosine monophosphate was higher in CA1, as compared to that in CA2-4,DG. LysoPG and LysoPE were more abundant in CA1, while LysoPI 18:0 was detected only in CA2-4,DG. After IR, a substantial decrease in the citric acid level in CA1, an accumulation of pipecolic acid in both regions, and opposite changes in the amount of PE and LysoPE were observed. The following metabolic pathways were identified as being differentially active in control CA1 vs. CA2-4,DG: metabolism of taurine and hypotaurine, glycerophospholipid, and purine. These results may indicate that a regulation of cell volume, altered structure of cell membranes, and energy metabolism differentiate hippocampal regions. Early post-ischemia, spatial differences in the metabolism of aminoacyl-tRNA biosynthesis, and amino acids and their metabolites with a predominance of those which upkeep their well-being in CA2-4,DG are shown. Presented results are consistent with genetic, morphological, and functional data, which may be useful in further study on endogenous mechanisms of neuroprotection and search for new targets for therapeutic interventions.
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PMID:Hippocampal Sector-Specific Metabolic Profiles Reflect Endogenous Strategy for Ischemia-Reperfusion Insult Resistance. 3322 47