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)

Although oxygen free radicals have been implicated as mediators of cellular injury in myocardial ischemia-reperfusion, the exact nature of defects produced by these radicals is not clear. Because sarcolemmal Ca2+-pump is involved in the efflux of Ca2+ from the cell, this study was undertaken to examine the effects of oxygen free radicals on sarcolemmal ATP-dependent Ca2+ accumulation and Ca2+-stimulated Mg2+-dependent adenosinetriphosphatase (ATPase) activities as well as lipid peroxidation of membrane phospholipids. Isolated rat heart sarcolemmal membranes were incubated with xanthine + xanthine oxidase [a superoxide anion radical (O2-)-generating system], H2O2, or H2O2 + Fe2+ [a hydroxyl radical (HO.)-generating system] and assayed for Ca2+-pump activities. O2- inhibited the Ca2+-pump activities in a time-dependent manner; a significant inhibition of Ca2+-stimulated ATPase activity was seen after 1 min of incubation. Superoxide dismutase showed a protective effect on depression in Ca2+-pump activities caused by O2-.H2O2 inhibited Ca2+-pump activities in a dose-dependent manner; this inhibition was protected by the addition of catalase. HO. depressed the Ca2+-pump activities to a greater extent in comparison with H2O2. Mannitol showed a protective effect on HO.-induced inhibition of Ca2+-pump activities. The promotion of lipid peroxidation by free radicals was evident from increased formation of malondialdehyde. These results indicate that the sarcolemmal membrane is altered on exposure to oxygen free radicals, and this may result in depressing the Ca2+-pump mechanism for Ca2+ efflux from the myocardial cell.
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PMID:Depression of heart sarcolemmal Ca2+-pump activity by oxygen free radicals. 253 32

To understand the involvement of changes in sulfhydryl groups in causing depression of the sarcolemmal Ca2+-pump activities, this study was undertaken to examine the effects of oxygen free radicals on rat heart sarcolemmal sulfhydryl groups, Ca2+-stimulated adenosinetriphosphatase (ATPase), and ATP-dependent Ca2+ accumulation. In addition, the effects of sulfhydryl reagents such as dithiothreitol, cysteine, and N-ethylmaleimide on Ca2+-pump activities were investigated. The inhibition of sarcolemmal Ca2+-pump activities by O2-. (xanthine + xanthine oxidase) and H2O2 was decreased by the addition of dithiothreitol or cysteine in a dose-dependent manner. N-ethylmaleimide also showed inhibitory effects on Ca2+-pump activities both in a dose- and time-dependent manner; dithiothreitol and cysteine prevented changes in Ca2+-pump activities because of N-ethylmaleimide. Heart sarcolemmal sulfhydryl groups were depressed by O2-., H2O2, and .OH (H2O2 + Fe2+) both in a dose- and time-dependent manner. Superoxide dismutase, catalase, and D-mannitol showed protective effects on the sulfhydryl group depression by O2-., H2O2, and .OH, respectively. A significant correlation between changes in sarcolemmal Ca2+-stimulated ATPase activity and sarcolemmal sulfhydryl groups was seen. These results indicate that oxygen free radicals may depress the heart sarcolemmal Ca2+-pump activities by modifying the sulfhydryl groups in the sarcolemmal membrane.
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PMID:Mechanism for depression of heart sarcolemmal Ca2+ pump by oxygen free radicals. 255 Nov 90

Myocardial function in sepsis and endotoxin shock is reviewed. Clinical, whole animal, and isolated tissue studies are compared to answer the question whether sepsis and/or endotoxin directly damage the myocardium. Myocardial performance is considered relative to control of preload, afterload, and heart rate. Despite the fact that these vary widely in different studies, there is overwhelming evidence that myocardial performance is depressed in both sepsis and endotoxin shock. The depression is dose related, occurs early after large doses of endotoxin but may follow a hyperdynamic phase in sepsis or after low doses of endotoxin. Endotoxin itself does not appear to be the depressant factor; the final depressant substance(s) is unknown. Calcium transport by the sarcoplasmic reticulum is depressed. This defect is more prominent in the endocardium than in the epicardium. Myocardial adenosinetriphosphatase (ATPase) and norepinephrine stores may be depleted. The septic myocardium has an increased dependence on sympathetic nerve stimulation. There is little evidence that the cause of the myocardial depression is an inadequate coronary blood flow.
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PMID:Myocardial function in sepsis and endotoxin shock. 269 Jun 45

The mechanism of uncoupling of oxidative phosphorylation by carbonyl cyanide p-trifluoromethoxy)phenylhydrazone (FCCP), a typical weak acid protonophore, oleic acid, a fatty acid, and chloroform, a general anesthetic, has been investigated by measuring in mitochondria their effect on (i) the transmembrane proton electrochemical potential gradient (delta mu H) and the rates of electron transfer and adenosine 5'-triphosphate (ATP) hydrolysis in static head, (ii) delta mu H and the rates of electron transfer and ATP synthesis in state 3, and (iii) the membrane proton conductance. Both FCCP and oleic acid increase the membrane proton conductance, and accordingly, they cause a depression of delta mu H [generated by either the redox proton pumps or the adenosinetriphosphatase (ATPase) proton pumps]. Although their effects on ATP synthesis/hydrolysis, respiration, and delta mu H are qualitatively consistent with a pure protonophoric uncoupling mechanism and an additional inhibitory action of oleic acid on both the ATPases and the electron-transfer enzymes, a quantitative comparison between the dissipative proton influx and the rate of either electron transfer or ATP hydrolysis (multiplied by either the H+/e- or the H+/ATP stoichiometry, respectively) at the same delta mu H shows that the increase in membrane conductance induced by FCCP and oleic acid accounts for the stimulation of the rate of ATP hydrolysis but not for that of the rate of electron transfer. Chloroform (at concentrations that fully inhibit ATP synthesis) only very slightly increases the proton conductance of the mitochondrial membrane and causes only a little depression of delta mu H.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Uncoupling of oxidative phosphorylation. 1. Protonophoric effects account only partially for uncoupling. 282 53

Previous studies in hearts of female rats have demonstrated that ventricular hypertrophy due to systolic overload, when combined with hypertrophy induced by a chronic swimming program, results in increased cardiac performance and enhanced contractile protein activity compared with the effects of hypertension alone. To explore how a chronic running program affects the function of hypertensive hearts, renal hypertension was created in female rats, and the animals were subjected to a program of chronic treadmill running. Running alone caused enhanced cardiac function, an increase in myosin adenosinetriphosphatase (ATPase) activity, and an increase in the percent of the V1 myosin isoenzyme. Hypertension alone caused cardiac hypertrophy with a depression in myosin ATPase activity and a decrease in the percent of the V1 isoenzyme. Running improved cardiac function in hearts of normotensive rats but had no effect in hearts of hypertensive rats. Despite the diminished myosin ATPase activity in hearts of hypertensive runners and the decrease in percent of the V1 isoenzyme, cardiac function was well maintained. The results demonstrate that a chronic running program in hypertensive rats, in contrast to a chronic swimming program, had virtually no effect on cardiac performance or contractile proteins. The dissociation between myocardial performance and the contractile proteins implicates other biochemical mechanisms in the adaptations observed.
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PMID:Combined effects of hypertension and chronic running program on rat heart. 295 51

The primary objective of this study was to ascertain if various degrees of marked chronic food restriction (FR) as well as the combination of FR and exercise training of moderate intensity induce changes in the functional properties of the heart that are consistent with previously reported findings indicative of downregulation of high-adenosinetriphosphatase V1 isomyosin expression. Adult female rodents were randomly assigned to one of four experimental groups: 1) free eating, 2) 50% food restricted, 3) 75% food restricted, or 4) 50% food restricted plus treadmill trained. Results show that FR induced significant depression in the functional properties (heart rate, left ventricular pressure, rate of pressure development, and double product) of the heart in all FR groups and that this depression in functional capacity corresponded to the degree of FR. These functional changes were accompanied by significant downregulation of the alpha- and upregulation of the beta-myosin heavy chain gene expressions, as studied at both the mRNA and protein levels. The exercise training induced further alterations in cardiac function; however, these alterations occurred independently of any shifts in isomyosin composition. These results suggest that although severe FR is a potent stimulus to transform both the biochemical and functional properties of the rodent heart, the underlying mechanism(s) concerning these adaptations remains unresolved.
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PMID:Food restriction-induced transformations in cardiac functional and biochemical properties in rats. 845 75

This study determined whether dynamic exercise training of diabetic rats would increase the expression of the GLUT-4 glucose transport protein in prepared cardiac sarcolemmal membranes. Four groups were compared: sedentary control, sedentary diabetic, trained control, and trained diabetic. Diabetes was induced by intravenous streptozotocin (60 mg/kg). Trained control and diabetic rats were run on a treadmill for 60 min, 27 m/min, 10% grade, 6 days/wk for 10 wk. Sarcolemmal membranes were isolated by using differential centrifugation, and the activity of sarcolemmal K(-)-p-nitrophenylphosphatase (pNPPase; an indicator of Na(+)-K(+)-adenosinetriphosphatase activity) was quantified. Hearts from the sedentary diabetic group exhibited a significant depression of sarcolemmal pNPPase activity. Exercise training did not significantly alter pNPPase activity. Sedentary diabetic rats exhibited an 84 and 58% decrease in GLUT-4 protein and mRNA, respectively, relative to control rats. In the trained diabetic animals, sarcolemmal GLUT-4 protein levels were only reduced by 50% relative to control values, whereas GLUT-4 mRNA were returned to control levels. The increase in myocardial sarcolemmal GLUT-4 may be beneficial to the diabetic heart by enhancing myocardial glucose oxidation and cardiac performance.
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PMID:Exercise training increases sarcolemmal GLUT-4 protein and mRNA content in diabetic heart. 907 70

The Ca2+ uptake by isolated cardiac sarcoplasmic reticulum (SR) was compared between Richardson's ground squirrels and rats at 37, 25, 15, and 5 degrees C. The rate of SR Ca2+ uptake in ground squirrels was significantly higher than in rats over the temperature range. This marked species difference was observed over a Ca2+ concentration range from 0.1 to 10 microM. The Arrhenius plot for Ca2+ uptake was linear for ground squirrels between 37 and 5 degrees C but showed a depression from linearity for rats at 5 degrees C. This temperature sensitivity was also reflected in rat SR Ca2+-adenosinetriphosphatase activity. Analysis of [3H]ryanodine binding in SR suggests that more Ca2+ release channels are in an open state at low temperatures in rats than in ground squirrels. Together, these results suggest that species differences in the response of SR to low temperature may account for the rise in cytosolic free Ca2+ in cold-sensitive species and may be responsible, at least in part, for the inability of cold-sensitive hearts to function at low temperature.
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PMID:Ca2+ uptake by cardiac sarcoplasmic reticulum at low temperature in rat and ground squirrel. 914 10

Familial hemiplegic migraine (FHM) is a rare and genetically heterogeneous autosomal dominant subtype of migraine with aura. Mutations in the genes CACNA1A and SCNA1A, encoding the pore-forming alpha(1) subunits of the neuronal voltage-gated Ca2+ channels Ca(V)2.1 and Na+ channels Na(V)1.1, are responsible for FHM1 and FHM3, respectively, whereas mutations in ATP1A2, encoding the alpha2 subunit of the Na+, K+ adenosinetriphosphatase (ATPase), are responsible for FHM2. This review discusses the functional studies of two FHM1 knockin mice and of several FHM mutants in heterologous expression systems (12 FHM1, 8 FHM2, and 1 FHM3). These studies show the following: (1) FHM1 mutations produce gain-of-function of the Ca(V)2.1 channel and, as a consequence, increased Ca(V)2.1-dependent neurotransmitter release from cortical neurons and facilitation of in vivo induction and propagation of cortical spreading depression (CSD: the phenomenon underlying migraine aura); (2) FHM2 mutations produce loss-of-function of the alpha2 Na+,K+-ATPase; and (3) the FHM3 mutation accelerates recovery from fast inactivation of Na(V)1.5 (and presumably Na(V)1.1) channels. These findings are consistent with the hypothesis that FHM mutations share the ability of rendering the brain more susceptible to CSD by causing either excessive synaptic glutamate release (FHM1) or decreased removal of K+ and glutamate from the synaptic cleft (FHM2) or excessive extracellular K+ (FHM3). The FHM data support a key role of CSD in migraine pathogenesis and point to cortical hyperexcitability as the basis for vulnerability to CSD and to migraine attacks. Hence, they support novel therapeutic strategies that consider CSD and cortical hyperexcitability as key targets for preventive migraine treatment.
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PMID:Familial hemiplegic migraine. 1739 38


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