Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have shown a close temporal relationship between lipid abnormalities and membrane dysfunction in ischemia and that phospholipase-inhibiting drugs limit such derangements. Amiodarone is a potent phospholipase inhibitor, but its potential or that of any other inhibitor to simultaneously attenuate lipid abnormalities and electrophysiological changes in the very early phase of ischemia has never been studied. We therefore investigated simultaneously such changes in early ischemia. In isolated porcine hearts perfused with or without pure amiodarone solutions, electrophysiologic changes before and during 20 min of LAD occlusion were recorded using unipolar electrodes and Franz contact electrode catheters, and full thickness myocardial biopsies obtained for lipid analyses. In untreated hearts (n = 5), occlusion of LAD resulted in the rapid onset of TQ depression/ST elevation within 1 min and plateauing at 10 min. There were mean increases of 33% and 50% in lysophosphatidylcholine and 33% and 70% in lysophosphatidylethanolamine levels at 5-7 min and 20 min of ischemia, respectively. Non-esterified fatty acid (NEFA) content did not change significantly during the first 5-7 min, but increased by 75% after 20 min of LAD occlusion. In treated hearts (n = 5) there was a 37% increase in sinus cycle length after amiodarone administration (503 +/- 85 vs 689 +/- 115 ms, P < 0.01) but no significant change in ventricular effective refractory period (202 +/- 22 vs 204 +/- 21 ms), action potential duration (215 +/- 11 vs 217 +/- 7 ms), or amplitude (31 +/- 6 vs 28 +/- 3 mV) was observed. Also, amiodarone treatment did not alter total phospholipid content, lysophospholipids and NEFA levels of non-ischemic hearts. However, there was significant attenuation (P < 0.01) of the onset of the TQ/ST shift and preservation of action potential amplitude (P < 0.02) during the first 5-7 min of LAD occlusion with concomitant suppression of the increase in both lysophospholipids (hydrolysis products of membrane phospholipids by endogenous phospholipases) and NEFA levels observed after 5-7 and 20 min of ischemia. The results suggest that amiodarone can delay the onset and limit the extent of electrophysiologic change in early myocardial ischemia in temporal association with suppression of myocardial phospholipase activities.
J Mol Cell Cardiol 1993 Sep
PMID:Phospholipase inhibition and the electrophysiology of acute ischemia: studies with amiodarone. 828 71

Subcellular distribution of aminoacyl-tRNA synthetase activities has been studied in normal rabbit liver and under experimental myocardial ischemia (EMI). An increase in the activity of a number of aminoacyl-tRNA synthetases in postmitochondrial and postribosomal supernatants from rabbit liver has been determined 12 hr after EMI. Gel chromatography of the postribosomal supernatant on Sepharose 6B shows that aminoacyl-tRNA synthetase activities are distributed among the fractions with M(r) 1.82 x 10(6), 0.84 x 10(6) (high-M(r) aminoacyl-tRNA synthetase complexes) and 0.12-0.35 x 10(6). In the case of EMI aminoacyl-tRNA synthetase activities are partly redistributed from the 1.82 x 10(6) complex into the 0.84 x 10(6) complex. The catalytic properties of both free and complex leucyl-tRNA synthetases have been compared. KM for all the substrates are the values of the same order in norm and under EMI. A decrease in some aminoacyl-tRNA synthetase activities associated with polyribosomes has been observed 12 hr after EMI. The interaction of aminoacyl-tRNA synthetases with polyribosomes stimulates the catalytic activity of some enzymes and protects them from heat inactivation in vitro. It is assumed that the changes in association of aminoacyl-tRNA synthetases with high-M(r) complexes and compartmentalization of these enzymes on polyribosomes may be related to the alteration of protein biosynthesis under myocardial ischemia.
Mol Cell Biochem 1993 Aug 25
PMID:Subcellular distribution and properties of rabbit liver aminoacyl-tRNA synthetases under myocardial ischemia. 828 66

Previous studies have demonstrated that transforming growth factor-beta (TGF-beta) can accelerate wound healing, inhibit free radical formation and limit myocardial ischemia/reperfusion injury in a variety of experimental models. However, it is unknown whether exogenous TGF-beta 1 can attenuate the prolonged contractile dysfunction that is observed after a brief, reversible ischemic insult (myocardial stunning). Thus, open-chest dogs undergoing a 15-min left anterior descending coronary artery occlusion and 4 h of reperfusion were given TGF-beta 1 as an intravenous bolus (250 micrograms) at 24 h and again at 1 h before coronary occlusion (n = 5). Control dogs (n = 7) received equivalent amounts of vehicle. The two groups were similar with respect to occluded bed size, collateral blood flow and rate-pressure product. Fundamental physiological parameters, such as body temperature, arterial pH, PO2 and hematocrit, were within normal limits throughout the experiment. In control dogs, regional myocardial function (assessed as systolic thickening fraction) remained depressed throughout the 4 h reperfusion period, indicating severe myocardial stunning. TGF-beta 1 did not produce any significant improvement in the recovery of regional function; 4 h after reperfusion, paradoxical systolic thinning was still present in both treated and control groups, with thickening fraction being -22.5 +/- 6.1% and -31.0 +/- 5.3% of baseline, respectively (P = N.S.). These results demonstrate that a large dose of TGF-beta 1 given before ischemia fails to attenuate myocardial stunning in the open-chest dog, suggesting that this growth factor does not exert protective effects in the setting of reversible myocardial ischemia/reperfusion injury.
J Mol Cell Cardiol 1993 Apr
PMID:Effect of transforming growth factor-beta 1 on myocardial stunning in the intact dog. 834 Sep 31

Lipid peroxidation, presumably the result of free radical-mediated injury, has been shown to occur during myocardial ischemia and reperfusion. Since vitamin E is a very effective, naturally occurring, chain-breaking antioxidant, it was investigated whether a vitamin E-supplemented diet increased myocardial tolerance towards ischemia and reperfusion in pigs. In addition to a standard diet which contained 30 mg vitamin E/kg (approximately daily vitamin E intake 30 mg), ten pigs were fed with 10 g vitamin E (all-rac-alpha-tocopherol acetate, Merck AG, Darmstadt, Germany) daily for at least 4 weeks. Ten control pigs remained on the standard diet. In an open chest preparation, the left anterior descending coronary artery was distally ligated for 45 min followed by 3 d of reperfusion. Infarct size was determined as the ratio of infarcted (tetrazolium stain) to ischemic myocardium (dye technique). Regional systolic shortening was evaluated by sonomicrometry. Vitamin E concentrations in plasma and myocardium were measured by high-performance liquid chromatography. Global hemodynamic characteristics did not differ between the two groups. Oral pretreatment with vitamin E raised the plasma concentration of this vitamin from 1.1 +/- 0.3 to 5.0 +/- 1.0 mg/l and the myocardial content from 4.2 +/- 0.7 to 18.6 +/- 2.7 ng/mg fresh weight. Vitamin E treatment did not reduce infarct size, which amounted to 71.3 +/- 5% in the control group and to 71.7 +/- 8.2% in the treated animals. Furthermore, recovery of regional systolic shortening of the reperfused segment did not significantly differ in the two groups after 3 d of reperfusion; it measured 2 +/- 4% in the controls and 6 +/- 6% (p = 0.16) in the treated animals. Therefore, chronic, oral treatment with vitamin E which raised myocardial and plasma concentrations of this vitamin 4- to 5-fold did not increase myocardial tolerance towards ischemia and reperfusion in this animal model.
J Mol Cell Cardiol 1993 Jan
PMID:Failure of chronic, high-dose, oral vitamin E treatment to protect the ischemic, reperfused porcine heart. 844 Nov 76

Concerning cardiac contractile proteins, antigenicity and myocardiotogenicity were discussed. In normal states, these proteins are immunologically tolerant, and can not provoke any heart-specific disease. Why the proteins can provoke such lethal autoimmune myocarditis has not been completely elucidated. Shortly after cardiac infection or myocardial ischemia, these proteins may work as the antigen for the autoimmune myocarditis. First of all, the role of cardiac myosin has been strongly emphasized. But, the antigen determinants: epitope proteins remain unclear. Either cross-activity to the streptococcal M protein and/or the alpha-helical coiled-coil protein may be an important factor to determine antigenicity. In this autoimmune myocarditis, the roles of T-lymphocyte and cardiac dendritic cell are noticeable. Through further study on the relation between antigen epitope and the infectious agents in the heart; on cardio-cytotoxicity of the T-lymphocyte and on the precise contribution of cardiac dendritic cells, this autoimmune myocarditis will be more clarified.
Mol Cell Biochem 1993 Feb 17
PMID:Cardiac contractile proteins and autoimmune myocarditis. 845 88

We assessed the protection afforded against myocardial ischemia/reperfusion by nitecapone in the Langendorff heart model using male Sprague-Dawley rats. We found that when present in the perfusate 10 microM nitecapone improved the mechanical function of the heart and lowered the enzyme leakage of lactate dehydrogenase after 40 minutes of global ischemia. In nitecapone treated hearts the content of oxidized proteins and lipids (carbonyl groups and endogenous lipid fluorescent products) decreased. Nitecapone partially prevented the loss of total sulfhydryl groups and vitamin E after ischemia and reperfusion. We suggest that the mechanism of nitecapone protection most likely involves direct antioxidant action and enhancing the activity of other antioxidants.
Biochem Mol Biol Int 1993 Mar
PMID:Nitecapone protects the Langendorff perfused heart against ischemia-reperfusion injury. 848 62

To determine whether calcium channel blockade is effective in the prevention of the cascade of events leading to the thin walled, decompensated ventricle observed in ischemic heart failure, inhibition of transsarcolemmal transport of calcium by nisoldipine was examined in rats in which luminal narrowing of the left main coronary artery was utilized to produce global cardiac ischemia. Coronary artery narrowing was produced in rats at 2 months of age and animals were maintained on nisoldipine (10 mg/kg body weight) (CANN) or water (CANW) until time of sacrifice 1 month later. Surgical intervention resulted in a 50% reduction in coronary artery luminal diameter in both experimental groups and was associated with an increase in kidney and lung weights in only CANW animals. Heart weights were also increased in the water treated coronary artery narrowed group. In CANW rats, systemic arterial and left ventricular systolic pressures were reduced whereas left ventricular diastolic pressures were elevated. Peak rates of pressure rise and decay and cardiac output were also reduced in CANW rats. Treatment with nisoldipine prevented the detrimental impact of ischemic heart disease to an extent that all measured parameters in CANN rats were found to be intermediate between unoperated controls and CANW animals. Thus, calcium channel blockade was therapeutic in the prevention of cardiac dysfunction and failure seen after the onset of ischemic heart disease in rats. Furthermore, the detrimental impact of ischemic heart disease was ameliorated by early and continuous treatment with the calcium channel blocker, nisoldipine.
J Mol Cell Cardiol 1995 Sep
PMID:Nisoldipine improves ventricular function in rats with ischemic heart failure. 852 45

N-3 polyunsaturated fatty acids have been epidemiologically demonstrated to decrease the incidence of ischaemic heart disease. The present study was undertaken to examine the effects of long-term treatment with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on hypoxia/reoxygenation injury of isolated adult rat cardiomyocytes. Rats, fed with standard rat chow, were treated with 100 to 1000 mg/kg/day EPA or 1000 mg/kg/day DHA for 4 weeks and their cardiomyocytes were isolated by collagenase treatment. The cardiomyocytes, approximately 90% of which were rod-shaped, were subjected to 150-min hypoxia/15-min reoxygenation, and their survivals at the ends of hypoxia and reoxygenation were determined. Treatment with either 1000 mg/kg/day of EPA or DHA resulted in a significant increase in the survival of the cardiomyocytes (39.9 +/- 1.1 and 38.3 +/- 3.0%, n = 14 and 8, respectively v 26.7 +/- 1.6%, n = 8, for untreated group). Treatment with EPA increased eicosapentaenoic (377% increase), oleic (25% increase) and linoleic acid (37% increase) contents in the myocardial total phospholipids without changes in the total phospholipid content, whereas treatment with DHA did not increase DHA incorporation into the myocardial phospholipids. The results suggest that EPA and DHA protect the myocardial cells against hypoxia-reoxygenation-induced injury. Although alterations in myocardial phospholipid composition were observed by treatment with EPA or DHA, the primary mechanism underlying the benefit of EPA or DHA intake is unlikely to be related to increased incorporation of their own fatty acids into the myocardial phospholipids, or the mechanism may be different in each n-3 unsaturated fatty acid employed.
J Mol Cell Cardiol 1995 Sep
PMID:The effects of long-term treatment with eicosapentaenoic acid and docosahexaenoic acid on hypoxia/rexoygenation injury of isolated cardiac cells in adult rats. 852 62

Earlier studies by Rouslin and coworkers showed that, during myocardial ischemia in slow heart-rate species which include rabbits and all larger mammals examined including humans, there is an IF1-mediated inhibition of the mitochondrial ATPase due to an increase in the amount of IF1 bound to the ATPase (Rouslin, W., and Pullman, M.E., J. Mol. Cell. Cardiol. 19,661-668, 1987). Earlier work by Guerrieri and colleagues demonstrated that IF1 binding to bovine heart ESMP was accompanied by parallel decreases in ATPase activity and in passive proton conduction (Guerrieri, F., et al., FEBS Lett. 213, 67-72, 1987). In the present study rabbit was used as the slow heart-rate species and rat as the fast heart-rate species. Rat is a fast heart-rate species that contains too little IF1 to down regulate the ATPase activity present. Mitochondria were prepared from control and ischemic hearts and ESMP were made from aliquots by sonication at pH 8.0 with 2 mM EDTA. Oligomycin-sensitive ATPase activity and IF1 content were measured in SMP prepared from the control and ischemic mitochondrial samples. After identical incubation procedures, oligomycin-sensitive ATPase activity, oligomycin-sensitive proton conductivity, and IF1 content were also measured in ESMP samples. The study was undertaken to corroborate further what appear to be fundamental differences in ATPase regulation between slow and fast heart-rate mammalian hearts evident during total myocardial ischemia. Thus, passive proton conductivity was used as an independent measure of these regulatory differences. The results show that, consistent with the low IF1 content of rat heart cardiac muscle mitochondria, control rat heart ESMP exhibit approximately twice as much passive proton conductivity as control rabbit heart ESMP regardless of the pH of the incubation and assay. Moreover, while total ischemia caused an increase in IF1 binding and a commensurate decrease in passive proton conductivity in rabbit heart ESMP regardless of pH, neither IF1 content nor proton conductivity changed significantly in rat heart ESMP as a result of ischemia.
 ...
PMID:ATPase activity, IF1 content, and proton conductivity of ESMP from control and ischemic slow and fast heart-rate hearts. 859 81

The purpose of this study was to evaluate the protective effect of a new endotoxin analogue, monophosphoryl lipid A (MLA) in a rabbit model of myocardial ischemia/reperfusion and to show if this protection was mediated via synthesis of 70 kDa heat shock protein (HSP 70). Three groups of New Zealand White rabbits underwent 30 min coronary occlusion, followed by 4 hours reperfusion. First group of rabbits (n = 6) were treated with 0.35 ml vehicle (40 % propylene glycol, 10 % ethanol in water). The second and third group of rabbits (n = 6-8) were treated with MLA (35 micrograms/kg, i.v.) 12 and 24 hours prior to ischemia and reperfusion. MLA treatment either 12 or 24 h prior to ischemia/reperfusion demonstrated significantly reduced infarct size (12.5 +/- 1.7 and 14.7 +/- 2.1% for 12 and 24 h) when compared with vehicle control (40.4 +/- 8.6%, mean +/- S.E.M, p < 0.05). No significant differences in the infarct size was observed between the 12 and 24 h MLA treated groups. The area at risk was not significantly different between the three groups. Baseline values of heart rate, systolic and diastolic blood pressure were not significantly different between the control and MLA treated groups. However, the systolic as well as diastolic blood pressure during reperfusion were significantly lower in rabbits treated with MLA. Western blot analysis of the protein extracts of the hearts (n = 2/group) demonstrated no increase in the expression of the inducible form of HSP 70 following treatment with MLA. We conclude that MLA has significant anti-infarct effect in rabbit which is not mediated by the cardioprotective protein HSP 70. The anti-infarct effect of this drug is superior to the reported protective effects of delayed ischemic or heat stress preconditioning. We hypothesize that the pharmacologic preconditioning afforded by MLA is accomplished via a unique pathway that bypasses the usual intracellular signaling pathways which lead to the myocardial protection with the expression of heat shock proteins.
Mol Cell Biochem 1996 Mar 09
PMID:Monophosphoryl lipid A induces pharmacologic 'preconditioning' in rabbit hearts without concomitant expression of 70-kDa heat shock protein. 870 70


<< Previous 1 2 3 4 5 6 7 8 9 10