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)

1. Changes of structural proteins in experimental and human myocardial infarction were studied by the determination of myosin- and actomyosin-ATPase activities and gel electrophoretic analysis in the presence of sodium dodecyl sulfate (SDS). 2. In animal experiments using dogs, the relative amounts of myosin and alpha-actinin decreased at 24 to 48 hours after coronary ligation, became lowest at 72 hours, and remained at this level for 2 weeks and returned to almost normal value at 28 days. 3. Myosin- and actomyosin-ATPase activities decreased rapidly during 24 to 48 hours after ligation with temporary increase in their activities in the initial stage of ischemia and followed the similar time course as that of the amounts of myosin and alpha-actinin. 4. SDS gel electrophoretic analysis of structural proteins of infarcted tissues of the human hearts obtained from 5 cadavers showed also marked decrease of the contents of myosin and alpha-actinin with relative preservation of actin, tropomyosin and troponin-T.
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PMID:Changes of cardiac structural proteins in myocardial infarction. 92 15

The purpose of this study is to clarify whether cysteine proteinases play an important role in the degradation of myocardial proteins in the infarcted tissue. We studied the effects of a cysteine proteinase inhibitor, Ep459, on degradation of cardiac structural proteins caused by ischemia due to coronary artery ligation for 24 h. Proteolytic effects of purified cysteine proteinases on isolated cardiac tissue were also examined. Using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, degradation of cardiac structural proteins, particularly of myosin heavy chain, alpha-actinin and troponin-I was observed in the infarcted tissue. Treatment with Ep459 significantly reduced protein degradation and total activity of cathepsins B and L in the infarcted tissue, compared with the findings in the untreated group. The electrophoretic pattern of the infarcted myocardium was similar to that of myofibrillar proteins degraded by cathepsins B and L. These results suggest that cysteine proteinases, particularly cathepsins B and L, are involved in degradation of myofibrillar proteins in myocardial infarction.
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PMID:Degradation of myocardial structural proteins in myocardial infarcted dogs is reduced by Ep459, a cysteine proteinase inhibitor. 300 24

The purpose of this study was to make clear the changes of structural proteins in the ischemic contracture muscle. Ischemia experiments were conducted on the forelimb of canines. Contracture proteins (myosin, actin, alpha-actinin) were isolated and analysed by using SDS-polyacrylamide gel electrophoresis. In the muscle group after 7-hour-ischemia, the muscle structural proteins were changed remarkably, along the time course after the release of tourniquet. After 7 days, myosin heavy chain decreased to 1/2 to 1/3 the original value. It was especially myosin heavy chain that changed remarkably among muscle structural proteins. Actin showed changes after 10-hour-ischemia.
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PMID:[The study of structural proteins in the ischemic contracture muscle]. 343 76

We studied the effects of propranolol on degradation of cardiac structural proteins resulting from ischemia induced by 24 h ligation of the coronary artery in dogs. Degradation of myocardial myosin heavy chain, alpha-actinin and troponin-I was used as an indicator of degradation of cardiac structural proteins. In dogs with left circumflex coronary artery ligation, propranolol, given orally in the dose of 10 or 30 mg/kg, significantly reduced degradation of cardiac structural proteins. This can be supported by the facts that treatment with propranolol, 10 or 30 mg/kg, reduced release of cathepsins B, L and D from lysosome to cytosol in the ischemic tissue and that the reduced acidity of the ischemic tissue was improved by treatment with propranolol, 30 mg/kg. In conclusion, propranlol delays the necrotic development of the severely ischemic myocardial tissue as shown by reduced protein degradation.
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PMID:Effects of propranolol on tissue necrosis in experimental myocardial infarction in dogs. 382 60

NCO-700 is a newly synthesized inhibitor of both cathepsin B and calcium-activated neutral protease. We examined whether NCO-700 inhibits degradation of myofibrillar proteins induced by cardiac ischemia in dogs anesthetized with pentobarbital. Cardiac ischemia was produced by complete occlusion of the left anterior descending coronary artery (LAD) for 3 or 6 hr. Myofibrils were prepared from the ischemic myocardium, in which LAD was occluded, and from the nonischemic myocardium, in which LAD was not occluded. Electrophoresis of myofibrils prepared from the ischemic myocardium revealed that there were many degradation bands of myofibrillar proteins as well as the bands corresponding to alpha-actinin (AN), the 55 kDa protein (55 K), actin (A), tropomyosin (TM), troponin I (TN I), myosin light chain 1 (LC1) and myosin light chain 2 (LC2). In addition, the content of AN, 55 K, A, TM, TN I, LC1 and LC2 in the ischemic myofibrils was lower than that in the nonischemic myofibrils. Treatment with NCO-700 at the total dose of 20 mg/kg, which was injected intravenously before and during ischemia, inhibited both appearance of the degradation bands and the decrease in the content of A, TM, TN I, LC1 and LC2 being produced by cardiac ischemia. NCO-700, however, did not inhibit the decrease in the content of 55K and AN being induced by ischemia.
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PMID:Inhibition with NCO-700, a protease inhibitor, of degradation of cardiac myofibrillar proteins during ischemia in dogs. 406 61

In this work we studied the alteration of Z-line alpha-actinin in striated skeletal muscle, under conditions of experimental ischemia, by immunohistochemical techniques. alpha-Actinin was extracted and purified from rabbit striated skeletal muscle and used, as an antigen, for the production of antibodies, in sheep. Electrophoresis was performed on PAA sla-gel and the Ag-Ab reaction test on agarose slab-gel (immunodiffusion). Antibodies were used for the indirect immunoperoxidase technique on semithin sections of rabbit striated skeletal muscle, included in in Araldehyde, and observed with phase-contrast microscopy. alpha-Actinin from ischemic muscle because of stenosis of the iliac artery, undergoes a progressive alteration, from the third hour of ischemia, going out of its usual sites. From the fifth to the eighth hour it gradually disappears until it leaves rare and residual points of positive reaction only in correspondence to the Z-lines.
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PMID:[Morphological changes alpha-actinin in skeletal striated muscle in the rabbit in experimental ischemia]. 676 19

The aim of this research is to show the alterations of alpha-actinin in rabbit myocardium after DMF treatment administered by forced inhalation. Z-lines observed with light and phase-contrast microscopy, appeared to be intact and they were clearly displayed by the indirect PAP-reaction. But if you consider that in normal muscle Z lines do not get coloured by the PAP-reaction without a previous light treatment with trypsin. It may be inferred that, in this case, The DMF has had the same effect as the trypsin, causing alteration to the protein structure. Besides the sarcomeric structure is undoubtedly altered by the DMF, causing alterations, in our opinion, similar to those found in rabbit skeletal muscle, under conditions of acute experimental ischemia.
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PMID:[Structural and ultrastructural changes in the rabbit myocardium exposed to dimethylformamide vapors]. 676 21

The decrease in Ca2+ responsiveness of myofilaments in stunned myocardium implies that there may be structural changes in proteins composing the contractile machinery. To elucidate the lesion in stunned myocardium, isolated guinea pig hearts were subjected to global ischemia at 37 degrees C and reperfused. SDS-PAGE revealed that the contents of desmin, alpha-actinin, and spectrin decreased in the myofibrillar fraction isolated from hearts reperfused after 60-minute ischemia compared with nonischemic control hearts. To examine the change of cytoskeletal proteins in stunned myocardium, immunohistochemical studies with antibodies against these proteins were performed after 15 minutes of ischemia. In stunned myocardium, the staining was largely intact, but there were some lesions where desmin was not stained and alpha-actinin and spectrin were only weakly identified. The percentage of normally stained areas in the myocardium (percent stained area), quantified by image processing, was significantly lower in stunned myocardium (79.6 +/- 3.6%, mean +/- SEM) than in nonischemic control myocardium (96.5 +/- 0.7%). Percent recovery of developed pressure significantly correlated with percent stained area (r = .82, P < .001). In hearts subjected to 15-minute ischemia but not reperfused, or in hearts reperfused with Ca(2+)-free solution after 15-minute ischemia, staining by the antibodies remained intact, suggesting that the change of the cytoskeletal proteins is mediated by Ca2+ overload during reperfusion. In hearts treated with the protease inhibitor leupeptin (50 mumol/L) or calpain inhibitor I (100 mumol/L), both developed pressure and staining were well preserved. These results indicate that contractile dysfunction in stunned myocardium has a strong correlation with the disappearance of cytoskeletal proteins that may be mediated by a Ca(2+)-dependent intracellular protease activated during reperfusion. The disruption of cytoskeletal proteins is a possible mechanism for stunning, although it may be a secondary effect of protease activation.
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PMID:Inhomogeneous disappearance of myofilament-related cytoskeletal proteins in stunned myocardium of guinea pig. 878 78

Our objective in experiments reported here was to identify myofilament proteins of rat hearts either lost or degraded by cardiac ischemia (15- or 60-minute duration) with and without 45 minutes of reperfusion. We correlated these changes with alterations in myofilament sensitivity to Ca2+ and maximum force generation. Protein degradation and loss were assessed by high-performance liquid chromatography, SDS-PAGE, Western blotting analysis, and amino acid sequencing. Compared with nonischemic control hearts, bundles of skinned fibers from hearts subjected to ischemia alone demonstrated a decrease in maximum force generation and an increase in sensitivity to Ca2+. These changes in function were increased with the duration of the ischemia and with reperfusion. With increasing duration of ischemia, there was an increased loss and degradation of myofibrillar alpha-actinin and troponin I (TnI) at its C-terminus. Alpha-actinin and TnI were most susceptible to ischemia, but with 60 minutes of ischemia/reperfusion, there was also degradation of myosin light chain-1 (MLC1) involving a clip of residues 1 to 19. The MLC1 degradation product was detected in the reperfusion effluent (along with troponin T, tropomyosin, and alpha-actinin) but not in the tissue with 60 minutes of ischemia with no reperfusion. Moreover, with ischemia the following proteins became associated with the myofibrils: GAPDH and proteins of the mitochondrial ATP synthase complex. Our results provide new evidence regarding the mechanism by which ischemia/reperfusion causes myocardial injury and support the hypothesis that an important element in the injury is altered activity and structure of the myofilaments.
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PMID:Breakdown and release of myofilament proteins during ischemia and ischemia/reperfusion in rat hearts: identification of degradation products and effects on the pCa-force relation. 946 97

Nitric oxide, produced in macrophages by the high output isoform inducible NO synthase (iNOS), is associated with cytotoxic effects and modulation of Th1 inflammatory/immune responses. Ischemia and reperfusion lead to generation of high NO levels that contribute to irreversible tissue damage. Ischemia and reperfusion, as well as their in vitro simulation by hypoxia and reoxygenation, induce the expression of iNOS in macrophages. However, the molecular regulation of iNOS expression and activity in hypoxia and reoxygenation has hardly been studied. We show in this study that IFN-gamma induced iNOS protein expression (by 50-fold from control, p < 0.01) and nitrite accumulation (71.6 +/- 14 micro M, p < 0.01 relative to control), and that hypoxia inhibited NO production (7.6 +/- 1.7 micro M, p < 0.01) without altering iNOS protein expression. Only prolonged reoxygenation restored NO production, thus ruling out the possibility that lack of oxygen, as a substrate, was the cause of hypoxia-induced iNOS inactivation. Hypoxia did not change the ratio between iNOS monomers and dimers, which are essential for iNOS activity, but the dimers were unable to produce NO, despite the exogenous addition of all cofactors and oxygen. Using immunoprecipitation, mass spectroscopy, and confocal microscopy, we demonstrated in normoxia, but not in hypoxia, an interaction between iNOS and alpha-actinin 4, an adapter protein that anchors enzymes to the actin cytoskeleton. Furthermore, hypoxia caused displacement of iNOS from the submembranal zones. We suggest that the intracellular localization and interactions of iNOS with the cytoskeleton are crucial for its activity, and that hypoxia inactivates iNOS by disrupting these interactions.
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PMID:Hypoxia inactivates inducible nitric oxide synthase in mouse macrophages by disrupting its interaction with alpha-actinin 4. 1296 Mar 52


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