Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The high speed supernatant (cell sap) obtained from ischemic livers is less efficient than normal in supporting protein synthesis in cell-free systems. Cell saps from ischemic livers contain a reduced amount of transfer-RNA; the transfer of leucine to the specific tRNA is impaired; the incorporation of leucyl-tRNA into protein is reduced, although less than the incorporation of the corresponding amino acid. The binding of aminoacyl-tRNA to ribosomal subunits and exogenous messengers (polyuridylic acid and uridyl-3'-5'-uridyl-3'-5'-guanosine), is less efficient with ischemic than with normal cells sap, thus indicating a defective activity of elongation factor 1. The total amount-and possibly the intracellular distribution-of elongation factor 2 is also altered in ischemic livers. These changes, which are the expression of a multifunctional deficit of ischemic cell sap, are in general correlated with the duration of ischemia and do not seem to appear around the "point of no return" of the ischemic liver cells.
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PMID:Protein synthesis in liver injury. Soluble factors of protein synthesis in the cytosol from ischemic rat liver. 126 41

Comparative studies of the state of aggregation and activity of tRNA-methyltransferases in cytosol (105,000 X g supernatant) from normal and ischemic rabbit liver and myocardium were carried out. The optimal conditions (pH, protein concentration, ionic composition of incubation mixture) for the determination of activity of tRNA-methyltransferases were elaborated. The protein fraction precipitated at 55% saturation of ammonium sulfate was shown to inherit the highest activity of tRNA-methyltransferases. In rabbit liver cytosol, the bulk of the tRNA-methyltransferase activity (approximately 50%) was found to be associated with high molecular weight complexes containing aminoacyl-tRNA-synthetases. The tRNA-methyltransferase activity was increased almost 1.4-fold both in the myocardium cytosol under total ischemia of isolated heart (30 min, 37 degrees C) and in liver cytosol under experimental myocardial infarction (EMI, occlusion of anterior coronary artery for 12 hours). Moreover, the labilization of high molecular weight complexes was observed: up to 80% of the tRNA-methyltransferase activity was localized in the fraction of lower molecular weight complexes and free enzyme fraction. In the total set of eight methylated nucleotides (products of submethylated tRNA methylation by liver enzymes), the decreased m1A content and the increased m7G and m1G contents were observed at EMI. It was assumed that the observed changes in the state of aggregation of tRNA-methyltransferases, in particular, their dissociation from the high molecular weight amino-acyl-tRNA-synthetase complexes are prerequisites for the suppression of protein biosynthesis under ischemic conditions.
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PMID:[Comparative characteristics of tRNA-methyltransferases from rabbit liver and myocardium under normal conditions and in experimental ischemia]. 266 25

Catalytic properties and thermostability of leucyl-tRNA-synthetase were studied both in free form and in the form of high molecular complexes, isolated from pig myocardium under normal state and after 15 min and 30 min ischemia. Km values of free and associated forms of leucyl-tRNA-synthetase were similar either in normal state or after 15-30 min ischemia. Complex-formation protected the enzyme from thermic inactivation under normal and ischemic conditions. Reverse redistribution of the leucyl-tRNA-synthetase activity was found in the fractions of free enzyme and high molecular complex depending on duration of ischemia.
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PMID:[Study of the properties of leucyl-tRNA synthetase from porcine myocardium in a normal state and in experimental ischemia]. 281 81

A number of aminoacyl-tRNA synthetases from rabbit liver during experimental myocardial infarction and from pig myocardium upon 15-min of autolysis were found to increase their activity in aminoacylation. Direct correlations between the activities of high molecular weight complexes and of the total extracts were not observed. It was shown that the specific activity of endogenous inorganic pyrophosphatase increased markedly during the ischemia of myocardium both in total myocardium extracts and in high molecular weight complexes.
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PMID:[Aminoacyl-tRNA-synthetases and their high molecular weight complexes in experimental myocardial ischemia]. 615 Apr 36

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

A 34-year-old female IDDM patient complained of chest oppression in hypoglycemic episodes and electrocardiograms revealed reversible ischemic changes occurring concomitantly with hypoglycemia. The ECG changes improved and the chest oppression disappeared following increasing blood glucose level by glucose intake. Master's double load test and treadmill load test were positive for ischemic changes. Radioisotopic myocardial scintigraphy by thallium and BMIPP did not show any filling defects and coronary angiography revealed no remarked stenosis in the coronary arteries. She had no mitochondrial tRNA(Leu) (A-->G) gene mutation at nucleotide position 3243, but both the patient and her mother had a G-to-A transition within the replication origin of the light strand at nucleotide position 5744 of the mitochondrial gene. As the patient's maternal family had no history of ischemic heart disease, it is not clear whether mitochondrial gene mutation at nucleotide position 5744 reflects the occurrence of cardiac ischemia. Some disorders of microcirculation in capillary vessels in cardiac muscles may occur in such patients.
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PMID:An IDDM patient who complained of chest oppression with ischemic changes on ECG in insulin-induced hypoglycemia. 959 72

There are some human diseases associated with mitochondrial DNA genome defect. Now many studies think that: oxygen radical resulting from oxidative phosphorylation(OXPHOS) disorder caused by myocardium ischemia and the increased OXPHOS induction damage mitochondrial DNA. Chronic damage accumulations lead to mitochondrial DNA deletion or point mutation in the end which show mitochondrial DNA 5.0 kb or 7.4 kb deletion and point mutation at position C15452A in the cytochrome b gene; the conservative sequence mutation of tRNA gene such as A4300G, C4320T point mutation in the tRNA Ilegene, A3243G point mutation in the tRNA leu gene etc result in defective contractile proteins whose persistent and inefficient contraction may increase the myocardium's metabolic demands for ATP and leads to cardiac hypertrophy. In this article, we review the study on the association of mitochondrial DNA mutation with ischemic cardiomyopathy and hypertrophic cardiomyopathy.
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PMID:[The research progress of the association of mitochondrial DNA mutation with cardiomyopathy]. 1253 76

Patient studies suggested that accumulation of pathogenic mitochondrial (mt) DNAs having large-scale deletion or point mutation and the resultant mitochondrial respiratory abnormalities are associated with a wide variety of disorders, such as mitochondrial diseases, neurodegenerative diseases, diabetes, and aging. Although the pathogenicities of these mtDNA mutations were proved by co-transmission of the mutant mtDNAs and respiration defects to human mtDNA-less cells, there is as yet no convincing reverse genetic evidence to explain whether accumulation of these pathogenic mutant mtDNAs in tissues is responsible for the expressions of various clinical phenotypes. In such situation, we have succeeded in generating mice with pathogenic deletion mutant mtDNA, named "mito-mice", by introduction of mitochondria with mtDNA which is deleted 4,696 bp (nt 7,759-12,454) including 6 tRNA genes and 7 structural genes (del-mtDNA). In the mito-mice, del-mtDNA was transmitted maternally, and its accumulation induced mitochondrial dysfunction in various tissues, resulting in mitochondrial disease phenotypes, such as low body weight, lactic acidosis, ischemia, myopathy, hart block, deafness, male infertility, and renal failure. Thus, mito-mice are the first model animal for mtDNA-based diseases, and the mice should be valuable for screening effective drugs and testing therapies.
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PMID:[Model mouse for mitochondrial DNA-based diseases]. 1919 48

Ischaemia associated reduction in local tissue pH is well documented but the mechanisms through which it influences cell survival remain poorly understood. Using renal epithelial HK-2 cells we demonstrate acidotic pH6.4 protects against oxygen glucose deprivation (OGD) induced cell death. Initial exploration of the mechanisms responsible using microarray analysis revealed acidotic inhibition of OGD induced aminoacyl-tRNA synthetase (ARS) gene expression. These genes are key components of protein translation, which was markedly attenuated by reduced pH. Inhibition of protein synthesis using the ARS inhibitor halofuginone or cycloheximide protected against OGD induced injury. To explore further we focussed on the transcription factor CREB, identified by pathway analysis of microarray data and observed a pH dependent decrease in OGD induced activation. Inhibition of CREB/CBP interaction prevented OGD induced isoleucyl-ARS (IARS) expression, reduced protein synthesis and protected against OGD induced cellular injury. In addition we also observed that acidotic pH attenuated the OGD induced pro-apoptotic unfolded protein response (UPR) activated gene DDIT3. We suggest that maladaptive activation of CREB and ARS gene expression, through the maintenance of protein synthesis contributes to ER stress and UPR activation and that acidotic pH through inhibition of CREB activation inhibits protein synthesis and ultimately UPR activated apoptotic signals.
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PMID:Inhibition of protein translation as a mechanism of acidotic pH protection against ischaemic injury through inhibition of CREB mediated tRNA synthetase expression. 2389 26

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


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