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)

We have previously demonstrated that in furazolidone-induced congestive heart failure in turkeys the specific Ca(2+)-ATPase activity of myocardial sarcoplasmic reticulum (SR) is 60% increased in compensation for a 50% depression in net Ca(2+)-sequestration activity. This study tested the hypothesis that SR Ca(2+)-uptake and Ca(2+)-ATPase activities were uncoupled in this cardiomyopathy because of increased Ca(2+)-release channel activity. A novel microassay was used to monitor Ca2+ transport by myocardial homogenates using the fluorescent Ca2+ dye indo 1 to indicate extravesicular ionized Ca2+. The method is applied to cyropreserved biopsy specimens of myocardium and requires only 50 mg tissue. Both SR Ca(2+)-pump and SR Ca(2+)-channel activity were estimated using the channel-inhibitor ruthenium red (RR) and the mitochondrial inhibitor sodium azide. The specificity of the RR inhibition was confirmed using ryanodine. Cardiomyopathy was induced in 2-week-old turkey poults by the addition of 0.07% furazolidone to their feed for 4 weeks. Compared with controls, myocardial maximal Ca(2+)-channel activity relative to maximal Ca(2+)-pump activity was 22% greater and duration of Ca(2+)-channel activity was 100% increased. However, the heart failure birds had 43 and 53% decreases in absolute maximal Ca(2+)-pumping and Ca(2+)-channel activities, respectively. The abnormal Ca(2+)-channel activity resulted in 200% greater time before initiation of net Ca2+ sequestration and 700% greater final myocardial Ca2+ concentrations. For all birds, the Ca(2+)-accumulating activity was highly correlated with Ca(2+)-release activity (all p less than 0.05). These data indicate that in this animal model of congestive heart failure there is defective SR Ca(2+)-channel function resulting in abnormal Ca2+ homeostasis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Myocardial calcium cycling defect in furazolidone cardiomyopathy. 166 32

The role and regulation of (Na, K)-ATPase in cardiac sarcolemma are relatively well recognized today. Less abundant information is available about the time sequence of ischaemia-induced changes in activity and properties of the enzyme. In our experiments global ischaemia to the rat heart induces a time-dependent decrease in the activity and maximum velocity (Vm) value of sarcolemmal (Na, K)-ATPase. The depression of enzyme activity is fast and is expressed as early as 15 min after the onset of ischaemia. After 30 min of ischaemia the Vm decrease slows, probably due to an 'adaptational' decrease of the Km value of the (Na, K)-ATPase. This phenomenon may be interpreted as a mechanism by which the enzyme attempts to keep functioning in a situation when the supply by ATP is deficient. The depression in (Na, K)-ATPase activity is an early indicator of sarcolemmal damage. It outruns the changes in permeability of the cardiac sarcolemma to calcium and predicts ultrastructural damage to myocytes induced by ischaemia.
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PMID:Features of the (Na, K)-ATPase of cardiac sarcolemma with particular reference to myocardial ischaemia. 166 53

1. Acetylcholine (ACh), 7.5 x 10(-5) M, and carbachol, 5 x 10(-6) M (CCh) depressed the frequency of miniature endplate potentials (m.e.p.ps) in the frog (Rana temporaria) sartorius neuromuscular junction with active acetylcholinesterase to about 50-55% of the controls. 2. A similar depression was produced by the nicotinic agonists, nicotine, suberyldicholine and tetramethylammonium. 3. The muscarinic agonists, oxotremorine, methylfurmethide and methacholine were without effect on m.e.p.p. frequency. The muscarinic antagonist, atropine and the nicotinic antagonist, (+)-tubocurarine, had no effect on the depression of m.e.p.p. frequency evoked by CCh. 4. The ganglionic blockers, benzhexonium and IEM-1119, were also without effect on the CCh-evoked depression of m.e.p.p. frequency. 5. Pretreatment of muscles with anticholinesterases did not prevent the CCh-induced drop in m.e.p.p. frequency. 6. The effect of CCh was proportionally the same as in the controls in preparations where the m.e.p.p. frequency was changed by elevation of K+ and in the presence of theophylline, noradrenaline, dibutyryl adenosine 3':5'-cyclic monophosphate (db cyclic AMP) and db cyclic GMP. 7. An inhibitor of Na+,K(+)-ATPase, ouabain, 5 x 10(-5) mol l-1, prevented or reversed the depression of m.e.p.p. frequency by CCh. However, the depression was present in a nominally K(+)-free medium. Insulin and adrenaline, which are considered to be Na+,K(+)-ATPase activators, were without effect on depression of m.e.p.p. frequency. 8. The depression of m.e.p.p. frequency by 5 x 10(-6) M CCh was the same at temperatures between 5 and 30 degrees C with a Q10 near to 1.0. When threshold amounts of CCh were used (6 x 10-7 and 3 x 10-7 M), the depression was less at higher temperatures.9. The receptive structures responsible for the CCh (or ACh)-evoked depression of m.e.p.p. frequency differ pharmacologically from muscarinic, nicotinic ganglionic and neuromuscular junction ACh-receptors as well as from the synaptic cholinesterase, in contrast to previous reports (Duncan & Publicover, 1979).The low temperature-dependence points to the possibility that physical rather than biochemical processes are limiting in this presynaptic effect of cholinomimetics.
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PMID:Depression of miniature endplate potential frequency by acetylcholine and its analogues in frog. 166 83

A monoclonal antibody against subfragment 2 (S-2) of smooth muscle myosin, designated MM-9, was generated and characterized. MM-9 potently inhibited subfragment 1 (S-1) release by papain proteolysis of myosin, suggesting that the epitope of MM-9 is at or very close to the S-1/S-2 junction. The depression of Ca2(+)- and Mg2(+)-ATPase activities of myosin at low ionic strength was significantly reduced by MM-9. MM-9 increased the acto dephosphorylated HMM ATPase activity about 3-fold. On the other hand, the antibody had no effect on the KCl-dependence of viscosity of monomeric myosin. These results suggest that the folding of the myosin rod is not the direct determinant of enzymatic activity, and that the subtle conformational change at the S-1/S-2 junction (head-neck region) plays a critical role in determining enzymatic activities.
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PMID:Alteration of the enzymatic properties of smooth muscle myosin by a monoclonal antibody against subfragment 2. 169 93

Steady-state levels of 12 S and 16 S mitochondrial (mt) rRNAs and four mRNAs (NADH dehydrogenase subunits 3 and 4/4L, cytochrome c oxidase subunit III, H(+)-ATPase subunits 6/6L) were estimated by hybridization of cellular RNA with cloned human mt DNA fragments during hypoxia of HeLa cells. When the partial pressure of oxygen (pO2) was shifted from 135 to 15 Torr, the level of all mRNAs coordinately decreased more than 95% in 48 h, while that of rRNAs remained virtually unchanged. mRNA levels recovered within 4-6 h of reexposure to normoxia. The depression was observed at pO2 less than 40 Torr, the physiological pO2 in peripheral tissues. During these transitions, the growth rate of HeLa cells and the copy number of mt DNA per cell remained unchanged. The degradation rate of mt mRNAs in the presence of cordycepin was not affected by pO2. In contrast to the in vivo results, the potential activity of transcription in isolated mitochondria assayed under optimum conditions was not affected by previous hypoxic exposure of the cells. These observations provide evidence for the existence of a new mechanism controlling mitochondrial gene transcription.
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PMID:Hypoxic depression of mitochondrial mRNA levels in HeLa cell. 170 27

The secA gene product is an autoregulated, membrane-associated ATPase which catalyzes protein export across the Escherichia coli plasma membrane. Previous genetic selective strategies have yielded secA mutations at a limited number of sites. In order to define additional regions of the SecA protein that are important in its biological function, we mutagenized a plasmid-encoded copy of the secA gene to create small internal deletions or duplications marked by an oligonucleotide linker. The mutagenized plasmids were screened in an E. coli strain that allowed the ready detection of dominant secA mutations by their ability to derepress a secA-lacZ protein fusion when protein export is compromised. Twelve new secA mutations were found to cluster into four regions corresponding to amino acid residues 196 to 252, 352 to 367, 626 to 653, and 783 to 808. Analysis of these alleles in wild-type and secA mutant strains indicated that three of them still maintained the essential functions of SecA, albeit at a reduced level, while the remainder abolished SecA translocation activity and caused dominant protein export defects accompanied by secA depression. Three secA alleles caused dominant, conditional-lethal, cold-sensitive phenotypes and resulted in some of the strongest defects in protein export characterized to date. The abundance of dominant secA mutations strongly favors certain biochemical models defining the function of SecA in protein translocation. These new dominant secA mutants should be useful in biochemical studies designed to elucidate SecA protein's functional sites and its precise role in catalyzing protein export across the plasma membrane.
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PMID:Isolation and analysis of dominant secA mutations in Escherichia coli. 182 69

A novel, simple, rapid and reproducible microassay is used for kinetic analysis of Ca-sequestration by homogenates of myocardium of turkeys with furazolidone-induced congestive cardiomyopathy. The assay monitors Ca in real-time using dual-emission ratiometric spectrofluorometry and the Ca-indicator dye indo-1. Using this assay and isolated SR studies we make several novel findings regarding the mechanism of SR failure in furazolidone cardiomyopathy. Qualitative differences in Ca-sequestration were not detected between groups. However, compared to controls the furazolidone treatment resulted in: 1) 50% depression in maximal activities (1.54 +/- 0.36 vs 0.73 +/- 0.12 microM/sec); 2) 2-fold increases in post-sequestration concentrations of ionized Ca (79 +/- 23 vs 141 +/- 13 nmol Ca/L homogenate); 3) 2-fold increases in Ca half-life (415 vs 790 msec); and 4) 25% increased passive Ca-binding capacity of homogenates. The Ca-ATPase specific activity of isolated sarcoplasmic reticulum was 60% increased in congestive cardiomyopathy (543 +/- 140 vs 873 +/- 108 nmol ATP hydrolyzed/min/mg membrane protein) although membrane yield was 20% decreased (0.79 +/- 0.09 vs 0.63 +/- 0.03 mg/g heart). The increased ATPase and decreased Ca-uptake activities in combination with the occurrence of 36% cardiac hypertrophy and 19% decreased body weights resulted in estimates of the relative energy cost to the animal for myocardial Ca transport being 5.5-fold increased with cardiomyopathy (20.5 vs 111 nmol ATP hydrolyzed per microM decrease of sarcoplasmic free Ca/kg body weight). These data indicate that congestive cardiomyopathy is associated with markedly increased permeability of sarcoplasmic reticulum to Ca and compensatorily increased Ca-ATPase activity. Accelerated energy consumption due to the increased energy cost of Ca transport and increased time of myocyte activation are predicted to predispose the myocardium to fatigue and irreversible failure.
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PMID:Myocardial Ca-sequestration failure and compensatory increase in Ca-ATPase with congestive cardiomyopathy: kinetic characterization by a homogenate microassay using real-time ratiometric indo-1 spectrofluorometry. 182 61

Saline extracts of burn eschar (CEBE) and normal skin (CENS) caused inhibition to mitochondrial respiration and inner membrane function. Ethyl acetate extracts from CEBE (D1) and CENS (D'1) caused depression of the Respiratory Control Ratio, (RCR), an inhibition of respiration rate in state 3 and stimulation to state 4 respiration. Excellent linear correlations exist between the degree of inhibition to state 3, rate of stimulation to state 4 respiration and the logarithm of doses of D1 and D'1. The effective dose ranges (0.75-0.25 mg/ml for D1 and 4-1 mg/ml for D'1) differ by one order of magnitude. The activity of NADH dehydrogenase and succinate dehydrogenase of mitochondria after incubation with the highest toxic dose of D1 or D'1 remained normal. Dinitrophenol (DNP)-stimulated respiration was moderately inhibited by D1 and D'1. No change of oligomycin-sensitive ATPase activity was demonstrated. Exogenous malondialdehyde (MDA) did not show any inhibitory effect. Preliminary studies show that D1 contains a family of free fatty acids (FFA). Incubation of normal mitochondria with D1 increased the content of saturated FFA and a decrease of unsaturated FFA. The role of other peroxidative products is under investigation.
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PMID:Inhibition of mitochondrial respiratory function by an organic solvent extractable component from an extract of burn eschar. 183 77

Reperfusion after reversible ischemia has been shown to result in prolonged depression of contractile function ("myocardial stunning"). Recent studies suggest that oxygen free radicals may mediate postischemic dysfunction. Since heart sarcolemmal membranes, which contain several types of enzymes, ion channels and receptors play important roles to maintain cell functions, the present study was undertaken to examine the effects of oxygen free radicals on heart sarcolemmal membrane functions in vitro. In the presence of a superoxide anion radical-generating system (2mM xanthine plus 0.03 U/ml xanthine oxidase), sarcolemmal Ca(2+)-stimulated ATPase activity and ATP-dependent Ca2+ accumulation were inhibited in an incubating time-dependent manner. Both lipid peroxidation (r = 0.82) and sulfhydryl group content (r = 0.95) showed significant correlations with Ca(2+)-stimulated ATPase activity. ATP-independent Ca2+ bindings were increased upon treating the membranes with xanthine plus xanthine oxidase. Voltage-dependent Ca(2+)-channels were also affected by oxygen free radicals. The maximal number of binding sites (Bmax) for [3H]-nitrendipine binding was depressed without any changes in dissociation constant (Kd). The effects of oxygen free radicals on adrenergic receptors were more complex. Bmax for [3H]-dihydroalprenolol (DHA) binding (beta-receptor) was increased whereas Bmax for [3H]-prazosin binding [alpha 1-receptor) was decreased after incubating the membrane with xanthine plus xanthine oxidase. Kd for [3H]-DHA or [3H]-prazosin binding was increased. Superoxide dismutase showed protective effects on the changes in these membrane functions due to xanthine plus xanthine oxidase. It is suggested that oxygen free radicals damage heart sarcolemmal membrane functions which may lead to cardiac dysfunction in the stunned myocardium.
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PMID:Stunned myocardium and oxygen free radicals--sarcolemmal membrane damage due to oxygen free radicals. 183 72

Male Wistar rats were fed an atherogenic diet for four months to investigate possible diet-induced lipid alterations and brain Ca2+ ATPase activity. Total cholesterol and triglyceride levels were found to be increased significantly in both serum and brain while the phospholipid level was decreased in both. The distribution of serum cholesterol between high-density and low-density lipoproteins was altered when compared to control rats with a decrement in HDL-cholesterol and a pronounced increment in LDL-cholesterol. The atherogenic diet resulted in about 50% depression in brain Ca2+ ATPase activity. It is concluded that alterations in ion transport and neurotransmitter release may be expected due to pronounced inhibition of brain Ca2+ ATPase activity in rats fed an atherogenic diet.
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PMID:Alterations in some lipid components and Ca2+ ATPase activity in brain of rats fed an atherogenic diet. 183 14


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