Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The results of our experiments demonstrated that one hour of ischemia followed by one hour of reflow in the kidney caused a reduction in (Na+K+)ATPase activity and microsomal sulfhydryl content as well as an increase in microsomal lipid peroxidation. Renal venous malondialdehyde concentration was increased soon after reperfusion of the ischemic kidney. All these changes were rectified by an infusion of 0.123 mmol N-(2-mercaptopropionyl)glycine/kg over a 70 min period. On the other hand, an in vitro addition of 0.01-0.5 mM N-(2-mercaptopropionyl)glycine to a membrane preparation in the presence of H2O2 and Fe3+ did not prevent but rather potentiated the free radical effect on the enzyme activity. However, addition of superoxide dismutase alone or with catalase together with 2-MPG were effective in preventing the enzyme depression induced by H2O2. The results therefore indicate that free radical generation participates in the evolution of ischemia/reperfusion cell injury and thiol-reducing agents may be beneficial in alleviating the cell damage in vivo.
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PMID:Effects of N-(2-mercaptopropionyl)glycine on ischemic-reperfused dog kidney in vivo and membrane preparation in vitro. 283 50

Global ischemia in guinea-pig hearts for 60 to 90 min depressed microsomal and mitochondrial Ca2+ uptake activities. Reperfusion of the 60 min ischemic hearts resulted in incomplete recovery of contractile function and calcium uptake activities of both mitochondrial and microsomal fractions. On the other hand, reperfusion of the 90 min ischemic hearts further depressed the microsomal Ca2+ uptake activity. Coronary occlusion for 90 min in dog hearts was found to decrease microsomal Ca2+-pump and sarcolemmal Na+-K+ ATPase activities. Reperfusion of these regional ischemic hearts further depressed the microsomal Ca2+ uptake and Ca2+-stimulated ATPase as well as sarcolemmal Na+-K+ ATPase activities whereas mitochondrial Ca2+ uptake was increased. Perfusion of rat hearts for 60 min with hypoxic medium resulted in depression of the sarcolemmal Na+-dependent Ca2+ uptake and ATP-dependent Ca2+ uptake activities. Reperfusion of these hypoxic hearts failed to recover the sarcolemmal Na+-Ca2+ exchange and Ca2+-pump activities. These results demonstrate that membrane defects with respect to Ca2+ transport processes in ischemic/hypoxic hearts may be associated with irreversible injury.
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PMID:Alterations in heart membrane calcium transport during the development of ischemia-reperfusion injury. 284 10

Heart sarcolemma has been shown to possess three catalytic sites (I, II and III) for methyl transferase activity (Panagia V, Ganguly PK and Dhalla NS. Biochim Biophys Acta 792:245-253, 1984). In this study we examined the effect of phosphatidylethanolamine N-methylation on ATP-independent Ca2+ binding and ATPase activities in isolated rat heart sarcolemma. Both low affinity (1.25 mM Ca2+) and high affinity (50 microM Ca2+) Ca2+ binding activities were decreased following incubation of sarcolemmal membranes with AdoMet under optimal conditions for site II and III. Similarly, Ca2+ ATPase activities measured at 1.25 mM and 4 mM Ca2+ were depressed by phospholipid N-methylation. S-adenosyl homocysteine, a specific inhibitor of phospholipid N-methylation, prevented the depression of low affinity Ca2+ binding and Ca2+ ATPase activities, whereas the methylation-induced effect on the high affinity Ca2+ binding was not influenced by this agent. Pretreatment of sarcolemma with methyl acetimidate hydrochloride, an amino group blocking agent, also prevented the methylation-induced inhibition of both Ca2+ binding and Ca2+ ATPase. A further decrease in Ca2+ binding and Ca2+ ATPase activities together with a marked increase in the intramembranal level of PC was seen when membranes were methylated under the site III conditions in the presence of phosphatidyldimethylethanolamine as exogenous substrate. There was no effect of phospholipid methylation on sarcolemmal Na+-K+ ATPase and Mg2+ ATPase activities. These results indicate a role of phospholipid N-methylation in the regulation of sarcolemmal Ca2+ ATPase and low affinity ATP-independent Ca2+ binding.
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PMID:Decreased Ca2+-binding and Ca2+-ATPase activities in heart sarcolemma upon phospholipid methylation. 284 56

The factors regulating calcium homeostasis in the cardiac plasma membrane of renal hypertension in the rat (two kidney-one clip, Goldblatt model) have been studied. Comparison of the cardiac sarcolemma from control (C) and hypertensive (H) rats indicates similar protein yield and purity. Study of longer term hypertension (4 to 12 weeks) shows a decrease in the number of calcium channel receptor binding sites (Bmax C: 549 +/- 122 fmol/mg; H: 334 +/- 74 fmol/mg) as well as a depressed calcium pumping ATPase activity (C: 7.6 +/- 2.5 nmol/mg/min; H: 3.8 +/- 1.5 nmol/mg/min). Furthermore, there is a decreased rate of Na+-Ca2+ exchange (C: 5.4 +/- 1.9 nmol/mg/5 s; H: 2.3 +/- 0.9 nmol/mg/5 s). Study of short-term hypertension (1 to 4 weeks) indicates that the earliest change occurs at 1 week with decreased calcium pumping ATPase due to a change of the Vmax of Ca2+ transport (C: 9.7 +/- 1.6 nmol/mg/min; H: 5.4 +/- 1.4 nmol/mg/min). This is then followed by the decreased calcium channel receptor binding. However, the rate and the extent of depression in Ca2+-ATPase activity are much greater than that of Ca2+ channel receptor binding. Since alteration of Ca2+-ATPase is accompanied by an increase in intracellular Ca2+ concentration and there is a temporal association with the onset of myocardial lesions in the hypertensive rats, it is suggested that elevated intracellular calcium concentration as a result of altered Ca2+-ATPase activity may play a significant role in the development of hypertensive cardiomyopathy.
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PMID:Altered calcium regulation in the cardiac plasma membrane in experimental renal hypertension. 284 6

1. LND 623 and LND 796 are two aminosteroid derivatives which exert similar positive inotropic effects to digitalis. Their electrophysiological, toxic and inotropic effects were investigated in both normal and partially K+-depolarized ventricular muscle. 2. In guinea-pig myocardial fibres, LND 623 and LND 796 required tenfold higher concentrations than digoxin to induce the same signs of toxicity; e.g. triggered activities generated from delayed afterdepolarizations, leading to the marked depression of action potential characteristics and inexcitability. These abnormal rhythms and delayed afterdepolarizations were abolished by 1 mM caffeine. The toxic effects were reversed by washout, particularly in the case of LND 796. 3. In normal-K+ solution, LND 623 and LND 796 exhibited concentration-dependent positive inotropic effects on guinea-pig papillary muscle and increased concomitantly resting membrane potential and action potential amplitude. The range of active concentrations (0.1 to 1 microM) of LND 623 was larger than that of digoxin (0.3 to 1 microM). Like digoxin, LND 796 exerted negative inotropic effects at the lowest concentrations (0.01 to 0.03 microM) and positive inotropic effects at high concentrations (1 and 3 microM). 4. In partially K+-depolarized papillary muscle, in the presence of 2 microM histamine, LND 623 (3 and 10 microM) and LND 796 (10 and 30 microM) enhanced the two components P1 and P2 of the contraction and increased slow action potential amplitude, resting potential and maximal rate of depolarization. Low concentrations (0.03 to 0.3 microM) of LND 796 induced negative inotropic effects. beta-Adrenoceptor blockade with atenolol (1 microM) did not modify the activity of LND 623 but significantly enhanced the negative inotropic effect on P2 induced by 1 and 3 microM LND 796 and reduced the positive inotropic effect on P1 and P2 of the highest concentration (30 microM) studied. 5. In the presence of either caffeine (1 mM) or Ca2+-free, Sr2+-rich (3.6 mM) solution, LND 623 and LND 796 produced a positive inotropic effect which was stronger with LND 623. 6. It is suggested that two mechanisms are involved in the inotropic effects of these aminosteroids: (i) an enhanced Ca2 + entry via the slow calcium channels partially brought about by a local release of endogenous catecholamines in the case of LND 796, (ii) an inhibitory effect on Na+-K+ ATPase which, at the highest concentrations, lead to similar signs of cellular toxicity to those described for digitalis drugs. Because of their enlarged positive inotropic range, both aminosteroids may be of interest in the treatment of congestive heart failure.
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PMID:Electrical and mechanical effects of new aminosteroids on guinea-pig isolated ventricular muscle. 285 56

Beta-adrenoceptor blocking agents may have, in addition to their primary action, also ancillary effects on the cell membrane. In the present paper the non-specific interaction of exaprolol with the ATPase systems in isolated rat heart sarcolemmal membranes was investigated. When preincubated with sarcolemmal membranes in vitro, exaprolol in concentrations below 10(-4) mol.l-1 had no significant effect on sarcolemmal Mg2+-, Ca2+- and (Na+ + K+)-ATPase activities. At exaprolol concentration of 10(-4) mol.l-1 the Mg2+- and Ca2+-ATPase activities became inhibited whereas the (Na+ + K+)-ATPase activity was markedly stimulated. A kinetic analysis of these interactions revealed a non-competitive inhibition of Mg2+- and Ca2+-ATPase. In the case of (Na+ + K+)-ATPase a synergistic type of stimulation characterized by an exaprolol-induced conversion of an essential sulfhydryl group in the active site of the enzyme to the more reactive [S-] form has been observed thus increasing the affinity of the enzyme to ATP. Exaprolol concentrations exceeding 5 X 10(-4) mol.l-1 induced an overall depression of the investigated enzyme activities.
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PMID:Exaprolol as a modulator of heart sarcolemmal (Na+ + K+)-ATPase. Evidence for interaction with an essential sulfhydryl group in the catalytic centre of the enzyme. 286 95

Using isolated polypeptides of the F0 sector of bovine heart mitochondrial H+-ATPase, antisera were developed detecting specifically two components of F0. These two components were identified as F0I and oligomycin-sensitivity-conferring protein (OSCP) respectively. Both F0I and OSCP were digested by mild trypsin treatment of submitochondrial particles depleted of the catalytic part of H+-ATPase (USMP). Proteolysis was largely prevented by binding of F1 to F0. Proteolysis of F0I resulted in the formation of three immunoreactive, membrane-bound fragments of apparently 26 kDa, 25.5 kDa and 18 kDa, respectively, indicating that F0I contains trypsin-accessible Arg or Lys residues located close to the end and the middle part of the protein, respectively, which are in intimate contact with F1. Digestion of USMP with trypsin resulted in depression of passive H+ conduction through F0 which could be ascribed to proteolysis of F0I.
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PMID:Topological and functional characterization of the F0I subunit of the membrane moiety of the mitochondrial H+-ATP synthase. 289 6

Single fast myotomal fibres and small bundles of slow fibres (from the adductor pectoralis profundus muscle) were isolated from the Antarctic teleost Notothenia neglecta. Fibres were skinned by a brief detergent treatment. The effects of phosphate on the mechanical properties and ATPase activity of fast and slow fibres were studied. 20 mM-phosphate inhibited maximum isometric tension in slow fibres by 34%, but by only 11% in fast fibres. A half-maximal response was obtained at approximately 5 mM-phosphate. These concentrations are within the range measured in muscle, and the effect is probably of physiological significance. This species is of particular interest, since there is evidence that the energy supply to the fast muscle is largely based on phosphocreatine breakdown, which would result in large changes in intracellular phosphate concentration during exercise. The maximum contraction velocity of both fast and slow fibres was not affected by 10 mM-phosphate, nor was the ATPase activity of the slow fibres during isometric contraction. The phosphate-induced depression in tension in slow fibres was associated with a proportional decrease in stiffness. The rate of force recovery after rapid, small amplitude stretches and releases was increased by phosphate, as was the rate of rise of force during stretch activation. The results are discussed with reference to the different patterns of energy supply for contraction in muscle, and an attempt is made at explaining the data in terms of changes in cross-bridge kinetics.
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PMID:Effects of phosphate on the contractile properties of fast and slow muscle fibres from an Antarctic fish. 293 48

One of the leading causes of mortality in diabetics is myocardial disease. In the past few years this subject has generated a significant amount of interest with the result that myocardial problems associated with diabetes are far better understood. Though originally thought to occur as a result of atherosclerosis, various studies have shown that heart disease can occur in the absence of atherosclerosis, suggesting a diabetic cardiomyopathy. Using diabetic animals, it has been possible to characterize diabetes-induced myocardial abnormalities. Diabetic rat hearts do not respond to conditions of high stress as well as controls. The functional depression is accompanied by altered cardiac enzyme systems. A decrease in myosin ATPase activity which appears to be a result of diabetes-induced hypothyroidism is seen. Also, a depression of sarcoplasmic reticular calcium ATPase, along with a depression of calcium uptake by the SR, is seen in diabetic rat hearts. Na+, K+ ATPase activity has also been shown to be depressed and the depression appears to correlate with depressed atrial contractility. High levels of circulating fats in diabetics may alter the integrity of membranes leading to altered enzyme activities. Insulin treatment has been relatively successful at reversing or preventing myocardial changes in the diabetic rat. Other treatments that have been studied include thyroid hormone treatment, since the depression of myosin ATPase can be corrected by such treatment; and carnitine treatment, as the elevation of long chain acyl carnitines (LCAC) and the resulting depression of calcium uptake in the SR can be so normalized. These treatments have not been successful at normalizing cardiac function. A combination of the two treatments normalized function only partially, suggesting that factors besides myosin ATPase and SR calcium uptake are involved. Other treatments that have been tried include vanadate, methyl palmoxirate, and choline and methionine. Vanadate treatment has proved to be encouraging in that it normalizes both function and hyperglycemia. Methyl palmoxirate, a fatty acid analog, normalized only the elevation of LCAC but did not affect function. Methionine and choline were only partially successful in preventing the functional alterations of diabetic rat hearts. The purpose of the present article is to review our understanding of diabetes-induced myocardial problems and their possible causes. Findings from our laboratory and others are described in which attempts have been made to normalize cardiac function.
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PMID:Diabetes-induced abnormalities in the myocardium. 293 41

The effect of a single dose of 5 mg/kg body weight of aflatoxin B1 on rat liver mitochondrial enzymes, succinate dehydrogenase (SDH) and Mg++ adenosine triphosphatase (Mg++-ATPase) and on certain lipids were studies at various intervals of time from 3 to 24 hours. A significant decrease in the specific activity of SDH was observed after 6, 12, 18 and 24 hr treatment. The Mg++-ATPase activity remained unaffected up to 12 hr but appreciably decreased after, 18 and 24 hr of the treatment. The level of phospholipids and cholesterol were not altered after 3, 6 and 12 hr treatment, thereafter (18 and 24 hr) an increase was observed in both the lipids following the aflatoxin treatment. Medroxyprogesterone acetate (MPA) did not cause any alteration in the specific activities of these enzymes as well as levels of cholesterol and phospholipids. The treatment with MPA caused significant increase in contents of cytochromes P-450, b5 and activities of Arylhydrocarbon hydroxylase (AHH), UDP-glucuronyl transferase (UDP-GT) and NADPH-cytochrome C-reductase of hepatic microsomes. It was observed that pretreatment with medroxyprogesterone acetate (MPA) could significantly minimuze the depression caused in mitochondrial SDH and Mg++-ATPase activities by aflatoxin B1.
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PMID:Modification of aflatoxin B1-induced changes in certain mitochondrial enzymes and lipids by medroxyprogesterone acetate. 294 74


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