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 influence of brain ischemia on the subcellular distribution and activity of Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) was studied in various cortical rat brain regions during and after cerebral ischemia. Total CaM kinase II immunoreactivity (IR) and calmodulin binding in the crude synaptosomal fraction of all regions studied increase but decrease in the microsomal and cytosolic fractions, indicative of a translocation of CaM kinase II to synaptosomes. The translocation of CaM kinase II to synaptic junctions occurs but not to synaptic vesicles. The translocation in neocortex and CA3/DG (dentate gyrus) is transient, whereas in the hippocampal CA1 region, it persists for at least 1 day of reperfusion. The Ca2+/calmodulin-dependent activity of CaM kinase II in the subsynaptosomal fractions of neocortex is persistently decreased by up to 85%, despite the increase in CaM kinase II IR. The decrease in activity is more pronounced than the decline in IR, suggesting that CaM kinase II is covalently modified in the postischemic phase. The persistent translocation of CaM kinase II in the vulnerable ischemic CA1 region indicates that a pathological process is sustained in the area after the reperfusion phase and this may be of significance for ischemic brain injury.
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PMID:Persistent translocation of Ca2+/calmodulin-dependent protein kinase II to synaptic junctions in the vulnerable hippocampal CA1 region following transient ischemia. 779 23

Antioxidative effects of the nitrovasodilator nicorandil (SG-75) and denitrated SG-75 (SG-86) were examined in vivo and in vitro. When the isolated rat liver was reperfused with Krebs-Henseleit solution after a 90-min ischemia, microsomal GSH S-transferase activity was increased significantly by oxidative modification of the sulfhydryl group of the enzyme. The increase in the transferase activity after ischemia/reperfusion was depressed by SG-75 but not by SG-86. Furthermore, only SG-75 significantly inhibited lipid peroxidation and the activation of microsomal GSH S-transferase induced by hydrogen peroxide treatment of liver microsomes. These data indicate that SG-75 has an antioxidative action and the nitro group of SG-75 may play a critical role for this action.
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PMID:Antioxidative action of the nitrovasodilator nicorandil: inhibition of oxidative activation of liver microsomal glutathione S-transferase and lipid peroxidation. 779 21

A variety of events, including inhalation of atmospheric chemicals, trauma, and ischemia-reperfusion, may cause generation of reactive oxygen species in the lung and result in airways constriction. The specific metabolic mechanisms that translate oxygen radical production into airways constriction are yet to be identified. In the lung, calcium homeostasis is central to release of bronchoactive and vasoactive chemical mediators and to regulation of smooth muscle cell contractility, i.e., airway constriction. In the present work, we characterized Ca(2+)-transport in the microsomal fraction of mouse lungs, and determined how reactive oxygen species, generated by Fe2+/ascorbate and H2O2/hemoglobin, affected Ca2+ transport. The microsomal fraction of pulmonary tissue accumulated 90 +/- 5 nmol Ca2+/mg protein by an ATP-dependent process in the presence of 15 mM oxalate, and 16 +/- 2 nmol Ca2+ in its absence. In the presence of oxalate, the rate of Ca2+ uptake was 50 +/- 5 nmol Ca2+/min per mg protein at pCa 5.9 (37 degrees C). The Ca(2+)-ATPase activity was 50-60 nmol Pi/min per mg protein (pCa 5.9, 37 degrees C) in the presence of alamethicin. Inhibitors of mitochondrial H(+)-ATPase had no effect on the Ca2+ transport. Half-maximal activation of Ca2+ transport was produced by 0.4-0.5 microM Ca2+. Endoplasmic reticulum Ca(2+)-pump (SERC-ATPase) was found to be predominantly responsible for the Ca(2+)-accumulating capacity of the pulmonary microsomes. Incubation of the microsomes in the presence of either Fe2+/ascorbate or H2O2/hemoglobin resulted in a time-dependent accumulation of peroxidation products (TBARS) and in inhibition of the Ca2+ transport. The inhibitory effect of Fe2+/ascorbate on Ca2+ transport strictly correlated with the inhibition of the Ca(2+)-ATPase activity. These results are the first to indicate a highly active microsomal Ca2+ transport system in murine lungs which is sensitive to endogenous oxidation products. The importance of this system to pulmonary disorders exacerbated by oxidative chemicals remains to be studied.
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PMID:Pulmonary microsomes contain a Ca(2+)-transport system sensitive to oxidative stress. 789 26

To evaluate the pathogenesis of lipid peroxidation in skin-flap necrosis and to select a novel herbal antioxidant to suppress lipid peroxidation and salvage the flaps, in vitro and in vivo experiments were instituted. In vitro studies revealed (1) the potentiality of the cutaneous microsomal system (vesicular fragment of endoplasmic reticulum) to generate oxyradicals by FeCl3 (oxidative agent), since NADPH-dependent lipid peroxidation was elevated time-dependently, (2) suppression of microsomal lipid peroxidation by herbal antioxidants (dose- and time-dependently), further supporting the theory of oxyradical-induced lipid peroxidation in the skin, and (3) that ellagic acid showed the strongest response, with curcumin, chlorogenic acid, and alpha-tocopherol (tocopherol) being moderate, and ferulic acid and gallic acid remaining weakest. Thus ellagic acid, curcumin, chlorogenic acid, and tocopherol at doses of 10, 60, 80 and 100 microM (twice I50, the dose which could inhibit lipid peroxidation by 50 percent) were chosen for in vivo assessments, respectively. In vivo studies were performed using rat back skin random flaps (70 x 15 mm and based anteriorly) and circular island flaps (20 mm in diameter and raised on superficial epigastric vessels). Control flaps were painted with a Tris-ethanol solution, and test flaps were painted with either ellagic acid, curcumin, chlorogenic acid, or tocopherol (above-mentioned doses per 250 microliters of Tris-ethanol per 300 mm2 of flap surface 1 hour before the operation and once a day for 3 postoperative days). Doses, frequency, and period of drug application were based on in vitro and in vivo pilot experiments. The results were as follows: (1) a direct and time-dependent relation was noticed between lipid peroxide levels and the rate of necrosis in both types of flap; (2) time-dependent elevation of lipid peroxide levels of skin, subcutaneous fat, and exudate of island flaps during ischemia and those of skin and subdermal fat after reperfusion indicated pre- and post-reflow states of lipid peroxidation rather than the original conception of merely reperfusion state; and (3) in good agreement with the results of in vitro experiments, ellagic acid exerted the strongest effect to suppress lipid peroxide levels of skin and to augment the viability of random flaps more than that of island flaps.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Involvement of lipid peroxidation in necrosis of skin flaps and its suppression by ellagic acid. 797 56

The activity of 1-alkyl-sn-glycero-3-phosphate (AGP) acetyltransferase was studied using microsomal fractions isolated from cerebral cortices of 15-day-old rabbits. Fraction P3A was isolated using buffered 0.32 M sucrose containing mercaptoethanol, EDTA and NaF. This fraction had specific AGP acetyltransferase activities which were 4.9-times those of microsomal fraction P3B isolated in 0.32 M sucrose alone. This P3B activity was increased 2.4-times after a preincubation in the presence of ATP, MgCl2 and a high-speed supernatant fraction from cerebral cortex. Further, the activities of both P3A and P3B were almost completely eliminated by preincubation in the presence of alkaline phosphatase. Thus an activation of the AGP acetyltransferase by phosphorylation was indicated. While there was little inhibition of the P3A AGP acetyltransferase in the presence of added ATP, the magnesium salt form of ATP (1 mM) was severely inhibitory, bringing about 86% inhibition for P3A and 91% for P3B. The inhibitory effects of MgADP and MgAMP were smaller, and MgATP was a much more effective inhibitor than MgCTP, MgGTP and MgUTP which brought about 20-38% inhibitions of P3A activity at 1 mM concentrations. The effect of MgATP may be of particular relevance to the synthesis of platelet activating factor (PAF) following a period of ischemia in brain. Falling MgATP levels during energy failure could relieve the inhibition of AGP acetyltransferase seen in healthy cells and allow the formation of 1-alkyl-2-acetyl-sn-glycero-3-phosphate, which is the first committed intermediate in the de novo pathway of PAF synthesis.
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PMID:MgATP inhibits the synthesis of 1-alkyl-2-acetyl-sn-glycero-3-phosphate by microsomal acetyltransferase of immature rabbit cerebral cortex. 801 76

Renal ischemia causes redistribution of Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase) to the apical membrane of proximal tubules. We determined the time course of regeneration of Na(+)-K(+)-ATPase polarity and sought evidence of increased enzyme production during recovery as a means to restore polarity. Anesthetized rats underwent 45 min renal ischemia and reflow of 15 min, 2 h, 6 h, and 24 h. Immunofluorescent and electron microscopy showed loss of strict basolateral localization of Na(+)-K(+)-ATPase at 15 min reflow with repolarization by 24 h in sublethally injured cells. Both alpha 1- and beta-subunits were only in microsomal fractions at all reflow intervals. Immunodetectable levels of both subunits declined to 60-70% of control by 24 h reflow. Levels of mRNA for each subunit declined in parallel through 24 h to 55% of control. Overall transcription was profoundly depressed through 6 h but had recovered to near control by 24 h. Specific transcription of alpha 1- and beta-subunit mRNA was markedly decreased after ischemia and only partially recovered by 24 h. These results suggest that recycling of misplaced units rather than new Na(+)-K(+)-ATPase production is the means by which renal epithelia initially repolarize after ischemic injury.
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PMID:Expression and molecular regulation of Na(+)-K(+)-ATPase after renal ischemia. 804 68

The activity of Na+,K(+)-ATPase in the microsomal fraction of rabbit kidney cortex was strongly decreased by ischemia and increased slightly, but not significantly, after reperfusion. These changes were correlated with a dramatic increase in lipid peroxidation in microsomes isolated from both ischemic and reperfused kidneys. This correlation may point to irreversible impairment of the enzymatic function under the influence of either oxygen free radicals or lipid peroxidation.
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PMID:Na+,K(+)-ATPase activity of rabbit kidney cortex membranes in ischemia and reperfusion. 814 Aug 29

Rat experiments have shown preliminary administration of phenobarbital and zixoryn (before ischemia) fails to prevent the hepatic monoxygenase system from ischemic lesion, followed by profound destructive changes in the liver, though the functional activity of the microsomal system remained high. Phenobarbital and zixoryn induction of monooxygenases in the postischemic period contributed to the complete restoration of the levels of microsomal cytochromes and the metabolic activity of xenobiotics in the liver just in its early periods. It is concluded that it is advisable to use the inductors in the postischemic restorative period to correct the detoxifying function of the liver.
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PMID:[The correction of the liver detoxifying function with phenobarbital and ziksorin before and after ischemia]. 831 5

Phospholipases A2 comprise a family of enzymes that hydrolyze the acyl bond at the sn-2 position of phospholipids to generate free fatty acids and lysophospholipids. In the central nervous system products of PLA2 regulate neurotransmission. In addition, the lysophospholipids, free fatty acids, eicosanoids, platelet activating factor and reactive oxygen species, generated by enhanced PLA2 activity and arachidonic acid metabolism, may be responsible for many destructive cellular processes in neuronal tissue. There are interactions between glutamate and PLA2 and its products which suggest that PLA2 activity plays an important role in excitotoxic neuronal cell injury associated with ischemia. Our laboratory has demonstrated that multiple forms of Ca(2+)-dependent PLA2 are present in the gerbil brain. These forms differ from previously described forms and from each other. After ischemia and reperfusion, cytosolic, mitochondrial/synaptosomal and microsomal PLA2 enzymatic activities are enhanced. These stable modifications of enzymatic activity cannot be explained by a direct effect of Ca2+ alone and our data suggest that regulatory influences other than Ca2+ may play an important role in PLA2 activation and mediation of cellular injury after an ischemic insult.
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PMID:Phospholipase A2 (PLA2) activity in gerbil brain: characterization of cytosolic and membrane-associated forms and effects of ischemia and reperfusion on enzymatic activity. 835 4

Presently we describe, for the first time, induction of microsomal heme oxygenase-1 (HO-1) mRNA and protein in response to ischemia/reperfusion and therefore define HO-1 as stress protein in the kidney. Specifically, Northern blot analysis of kidneys of rats subjected to bilateral ischemia for 30 min revealed an increase of 8- to 10-fold in the level of 1.8 Kb HO-1 mRNA 6 hr after reperfusion. The increase in transcript level was maintained when assessed after 24 hr. The levels of 1.3 and 1.9 Kb transcripts for the second isozyme of HO, HO-2, were decreased at both time points. The increase in HO-1 mRNA was reflected in HO-1 protein level, as judged by Western blot analysis and at the level of activity as judged by the rate of bilirubin formation. An absence of change in adrenal HO-1 mRNA level subsequent to renal ischemia/reperfusion suggested that the induction of kidney HO-1 did not reflect a generalized response of the rat organs to stress; rather, it was a target organ specific response. Moreover, in kidneys subjected to ischemia 6 and 24 hr after reperfusion, significant increases in the cellular content of heme were observed; heme is a known inducer of HO-1 synthesis. Ischemia/reperfusion also adversely affected concentration of cytochrome P-450 in both mitochondrial and the microsomal fractions of the kidney. We suggest that increase in tissue heme levels may be a significant factor in damage caused by ischemia/reperfusion to renal tissue, whereby the metalloporphyrin promotes oxygen-free radical formation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Induction of kidney heme oxygenase-1 (HSP32) mRNA and protein by ischemia/reperfusion: possible role of heme as both promotor of tissue damage and regulator of HSP32. 842 44


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