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)

Ubiquitin-protein conjugates in the hippocampus were analyzed by immunoblotting with a monoclonal anti-ubiquitin antibody. In the CA1 region, Triton X-100 insoluble ubiquitin-protein conjugates increased after 24 hr following 20 min of ischemia. When the total hippocampi were fractionated subcellularly, ubiquitin-protein conjugates increased in the particulate, especially in the mitochondrial fraction. The ubiquitin-protein conjugates were solubilized by SDS, or were partially solubilized by urea. The results indicate that insoluble ubiquitin-protein conjugates increase after ischemia.
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PMID:Subcellular distribution of ubiquitin-protein conjugates in the hippocampus following transient ischemia. 132 64

Triton X-100-, digitonin- and urea-insoluble ubiquitin conjugates (UC) in the mitochondrial fractions of the gerbil cortex and hippocampus were analysed. In the cortex, following 5 min of forebrain ischemia, UC increased at 30 min of reperfusion and returned to the control level at 24 h. Although chronological changes in UC in the hippocampus were similar to the cortex, a more sustained increase of UC was observed. Immunoblot analysis showed that UC above 50 kDa increased in both regions. The results indicate that insoluble UC increase in the early recovery stage after ischemic neuronal damages.
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PMID:Post-transient ischemia increase in ubiquitin conjugates in the early reperfusion. 132 67

The polar distribution of Na(+)-K(+)-ATPase to the basolateral membrane of proximal tubule cells is essential for the efficient and vectorial reabsorption of Na+ and may be dependent on the formation of a metabolically stable, detergent-insoluble complex of Na(+)-K(+)-ATPase with the actin membrane cytoskeleton. The present studies utilized immunocytochemical techniques to demonstrate and quantify the apical redistribution of Na(+)-K(+)-ATPase during mild ischemia (15 min) that occurred in proximal (1.3 +/- 0.9 vs. 4.5 +/- 1.1 particles/100 microns surface membrane, P less than 0.01) but not distal tubule cells. Treatment of control apical membranes with 2-(2-methoxyethoxy)ethyl 8-(cis-2-n-octylcyclopropyl)octanoate (A2C), a fluidizing agent, markedly increased membrane fluidity without any effect on Na(+)-K(+)-ATPase activity. In brush-border membrane vesicles isolated after ischemia, however, A2C further increased an already elevated Na(+)-K(+)-ATPase activity. During ischemia, total cellular Na(+)-K(+)-ATPase activity remained unaltered, but the Triton X-100-soluble (noncytoskeleton associated) fraction of Na(+)-K(+)-ATPase increased significantly following 15 and 30 min. There was a corresponding decrease in the Triton X-100-insoluble fraction of Na(+)-K(+)-ATPase, with the ratio of detergent-soluble to -insoluble Na(+)-K(+)-ATPase increasing from 13 +/- 2 to 32 +/- 5% (P less than 0.01) during 30 min of ischemia. Western blot analysis of the Triton X-100-soluble fraction, following 30 min of ischemic injury, revealed the presence of Na(+)-K(+)-ATPase, actin, fodrin, and uvomorulin. However, in a fraction highly enriched for Na(+)-K(+)-ATPase, neither actin, fodrin, nor uvomorulin was detected.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytoskeleton disruption and apical redistribution of proximal tubule Na(+)-K(+)-ATPase during ischemia. 132 35

The interrelation between intracellular cAMP content and activity of lysosomal hydrolases was studied in rat liver and heart during ischemia of varying genesis and after recirculation. The activity of acid phosphatase (AP) and cathepsin D (CD) was determined in the fraction enriched with lysosomes (FEL) and in the supernatant fraction (SF) at 30,000 x g. Ischemia of isolated perfused heart of 20 to 60 min as described by Langendorff was accompanied by an increase in the SF/FEL ratio. Postischemic reperfusion resulted in a further increase in this ratio. In a terminal state induced by cardiac arrest of 10 min and within the first postresuscitation hours the SF/FEL ratio in the rat liver also increased. Processing of the liver FEL with 0.025% concentration of detergent Triton X-100 was also indicative of lability of lysosomal membranes during recirculation. The intracellular cAMP content changed differently. During ischemia of the myocardium, the cAMP level rose by 40 min and remained increased after 20 and 40 min of reperfusion. The cAMP content in the liver decreased after 10 min of circulatory arrest and increased in the postresuscitation period achieving its peak 4 h after resuscitation. Intra-abdominal injection of lyposomes with incapsulated cAMP to rats in the postresuscitation period and the study of the effect of dibutyryl-cAMP, caffeine and isoproterenol on the activity of acid hydrolases of ischemic heart and after postischemic reperfusion showed that an increase in the cAMP content achieved in various ways was conducive to stabilization of lysosomal membranes.
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PMID:Role of cAMP in regulation of activity of acid hydrolases of rat heart and liver during ischemia and after recirculation. 166 65

The authors investigated the high affinity binding of [3H] muscimol to the receptor of synaptic plasma membranes (SPM) isolated from a normoxic and ischemic brain. Brain ischemia enhanced the [3H] muscimol binding to the receptor, located in native (Triton X-100 untreated) membranes. Scatchard's analysis showed that the total number of binding sites (BMAX) and the KD value increased by about 60%. The higher KD value persisted during 20 min of the reperfusion period. Concomitantly, ischemia stimulated the activity of phospholipase C and phospholipase A2, acting against phosphatidylinositol (PI). The degradation of PI and a transient accumulation of docosahexaenoic and arachidonic acids may be important factors involved in the modification of high affinity agonist binding to the GABAA receptor of SPM isolated from the brain submitted to ischemia.
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PMID:Brain ischemia increased high affinity binding of [3H]muscimol into synaptic plasma membrane receptor. 196 57

A previously validated small mammal trauma model, hind-limb ischemia secondary to infrarenal aortic ligation in the rat, was utilized to investigate the effects of traumatic injury on hepatic glucuronidation activity. As was previously observed with hepatic oxidative drug metabolism, model trauma resulted in a significant decrease in the in vivo glucuronidation of chloramphenicol, with a 23% drop in clearance of this drug. The effect on in vivo pharmacokinetics appeared to result from a complex interaction between trauma's differential influences on conjugating enzyme(s), deconjugating enzyme(s), and hepatic UDP-glucuronic acid levels, as well as the relative physiological importance of these variables. Hepatic UDP-glucuronyltransferase activities towards both p-nitrophenol and chloramphenicol were elevated (44-54%) after model injury when measured in native hepatic microsomes. However, microsomes which had been "activated" by treatment with Triton X-100 showed no significant difference between control and traumatized animals. Serum beta-glucuronidase activities were elevated by 58%, while hepatic beta-glucuronidase rose by about 16%. Nevertheless, in vivo deconjugation showed no significant change. Model trauma also resulted in a 46% decrease in hepatic UDP-glucuronic acid content. Thus, the observed post-traumatic depression of in vivo chloramphenicol glucuronidation could be due either to a diminished availability of a necessary cofactor (UDP-glucuronic acid) or to an alteration in enzyme kinetics or function in vivo.
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PMID:Effects of model traumatic injury on hepatic drug metabolism in the rat. IV. Glucuronidation. 286

Free arachidonic acid is released rapidly in the brain at the onset of ischemia and during convulsions. The transient nature of this phenomenon indicates the existence of an active reacylation system for this fatty acid, likely an arachidonoyl-CoA synthetase-arachidonoyl transferase. The first of these enzymatic activities in brain microsomes was studied and it was found that [1-14C]arachidonic acid is rapidly activated and shows an absolute requirement for ATP and CoA. MgCl2 enhances this activity 10-fold. The optimum pH is 8.5, and the apparent Km values for the radiolabeled substrate, ATP, CoA, and MgCl2 are 36, 154, 8, and 182 microM, respectively. The apparent Vmax is 32.4 nmol/min/mg protein for arachidonic acid. The presence of Triton X-100 (0.1%) in the assay medium caused a significant reduction in apparent Km (9.4 microM) and Vmax (25.7 nmol/min/mg protein) values. The enzymatic activity is thermolabile with a T1/2 of less than 1 min at 45 degrees C and a maximal activity at 40 degrees C. The breaking point or transition temperature is 25 degrees C in an Arrhenius plot. The activation energies were 95 kJ/mol from 0 to 25 degrees C and 30 kJ/mol from 25 to 40 degrees C. Fatty acid competition studies showed inhibition by unlabeled docosahexaenoic and arachidonic acids with a Ki of 31 and 37 microM, respectively, in the absence and 18 and 7.7 microM in the presence of Triton X-100. Palmitic acid and oleic acid slightly inhibited the reaction whereas linoleic acid inhibited it to a moderate extent. It is concluded that this very active enzyme can activate arachidonic acid as well as docosahexaenoic acid in brain microsomes. In addition, this reaction may be involved in regulating the pool size of these free fatty acids in brain by rapid removal through activation, thus limiting eicosanoid formation. Moreover, the rapid formation of polyenoic acyl-coenzyme A may participate in the retention of essential fatty acids in the central nervous system.
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PMID:Kinetic properties of arachidonoyl-coenzyme A synthetase in rat brain microsomes. 663 46

The susceptibility of the lipids of canine cardiac sarcolemma to attack by soluble lysosomal lipases was studied to simulate in vitro the lipolytic injury that occurs during ischemia. The sarcolemmal fraction was incubated at 37 degrees C with the soluble portion of rat hepatic lysosomes (the lysosol) under conditions (pH 5.0, 5 mM ethylenediaminetetraacetic acid) appropriate for the activity of the major lysosomal lipases. Incubation of sarcolemma with lysosol resulted in a 78% lipolysis of sarcolemmal triacylglycerols, a lesser degradation of glycerophospholipids, and a parallel production of free fatty acids and lysophospholipids. The hydrolysis of sphingomyelin was negligible but was greatly stimulated (75%) by the addition of Triton X-100 (1 mg). Endogenous lipolytic activities of the sarcolemma did not contribute significantly to the observed lipid hydrolysis either in the presence or absence of detergent. The lipolysis of sarcolemmal triacylglycerols, glycerophospholipids, and sphingomyelin (Triton X-100 stimulated) were inhibited by varying concentrations of chlorpromazine. Thus cardiac sarcolemma is susceptible to hydrolysis of lysosomal lipases, and chlorpromazine inhibits this potentially injurious process.
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PMID:Hydrolysis of sarcolemma by lysosomal lipases and inhibition by chlorpromazine. 706 77

Ischaemia of the dog intestine lasting 1 h causes desquamation of the epithelium at the villus tips and congestion in the villus capillaries. The crypt cells are relatively undamaged. These changes are associated with a loss of active transport of organic solutes, determined in vitro, a reduction in mucosal sucrase activity and an abolition of glucose absorption in vivo. A profuse net loss of water and electrolytes into the lumen in vivo develops. The net sodium loss is due primarily to an inhibition of the lumen-blood flux of this ion, the blood-lumen flux being relatively unchanged. In uraemic dogs, the loss of urea into the lumen is the same in control and ischaemic loops, testifying to the lack of change in the unidirectional water flow from blood to lumen. Perfusion of the dog intestine with 1% Triton X-100 leads to morphological changes that have certain similarities with those provoked by ischaemia. Damage was restricted to the villus tips, protection from further alterations apparently being provided by a mucus layer that forms on the mucosal surface; the crypt region remained unchanged. After 10 min exposure, organic solute transport in vitro and glucose absorption in vivo were both reduced by not abolished; sodium and water absorption in vivo were suppressed, but no net secretion occurred. To account for these observations, we have suggested that the normal crypt cell is a secretory element with respect to sodium and water. During maturation, its absorptive properties develop such that the mature enterocyte, possessing both absorptive and secretory mechanisms, is capable of net absorption of sodium. After destruction of the villus tips, net secretion continues in the crypts; if there are insufficient villus cells remaining to ensure reabsorption, a net secretory capacity is observed.
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PMID:Source of net water and electrolyte loss following intestinal ischaemia. 736 61

Binding of a variety of ligands for brain excitatory amino acid receptors was examined in membrane preparations extensively washed and treated with Triton X-100 that were obtained from the hippocampus and cerebral cortex of gerbils that survived for different periods after transient global brain ischemia. Bilateral occlusion of the carotid arteries for 5 min did not affect the binding of [3H](+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imi ne (MK-801) to an open ion channel associated with the N-methyl-D-aspartate (NMDA)-sensitive subclass in both central structures of gerbils that survived for 1 to 4 weeks after the injury when determined at equilibrium in the presence of 3 different endogenous agonists including L-glutamic acid (Glu), glycine (Gly) and spermidine at maximally effective concentrations. In contrast, the ischemic occlusion significantly diminished [3H]MK-801 binding when determined before equilibrium in the presence of the 3 stimulants in hippocampal membranes without altering that in cortical membrane 2 weeks after the insult, so that the initial association rates were invariably reduced by more than 60%. Moreover, the occlusion not only reduced the binding of both [3H]Glu and [3H]D,L-(E)-2-amino-4-propyl-5-phosphono-3-pentenoic acid to the NMDA domain on the NMDA receptor ionophore complex, but also decreased the binding of both [3H]Gly and [3H]5,7-dichlorokynurenic acid to the Gly domain. However, the insult did not induce any detectable changes under the experimental conditions employed in either the binding of [3H]DL-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) to the AMPA-sensitive subclass or the binding of kainic acid (KA) to the KA-sensitive subclass in both central regions of animals that survived for 2 weeks. These results suggest that transient global brain ischemia may predominantly impair neuronal and/or glial cells enriched of the NMDA receptor ionophore complex in gerbil hippocampus.
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PMID:Excitatory amino acid receptor binding in hippocampus of gerbils with transient global brain ischemia. 768 42


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