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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human placenta is an organ with a long period of growth in cell number later succeeded by cessation of cell division but some continued growth in cell size. The RNA concentration and content per cell (RNA/DNA ratio) are reduced between the end of the first trimester and the end of pregnancy, and there is a change in availability of placental chromatin for transcription when incubated in vitro with RNA polymerase II. Synthesis and secretion of placental peptide hormones on membrane-bound polyribosomes also undergo changes during pregnancy. During early pregnancy, levels of human chorionic gonadotropin are maximal, declining in later pregnancy, levels of human chorionic gonadotropin are maximal, declining in later pregnancy. The messenger RNA for this hormone undergoes similar changes in relative amount in the placenta. In contrast, the plasma level of placenta lactogen increases progressively during pregnancy, and in parallel with this, the placenta content of mRNA for this hormone increases throughout later pregnancy. It is concluded that placental programing regulates the relative amounts of mRNA for each hormone, and this in turn determines the amounts secreted at any stage of pregnancy. Nutritional status of the mother can affect placental RNA content, most clearly established in studies on rats in which a diet low in protein or with added alcohol results in a reduced capacity to form and secrete placental lactogen. The extent of this depression parallels the reduction in placental RNA content. It is suggested that underproduction of placental lactogen may be a factor in reducing flow of nutrients from the maternal tissues to the fetus in later pregnancy, under conditions of malnutrition.
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PMID:Placental protein and peptide hormone synthesis: impact of maternal nutrition. 735 83

Dolichol is an isoprenoid lipid involved in the assembly of many membrane-bound and secreted glycoproteins. Dolichol biosynthesis can be considered as a branch of the cholesterol biosynthetic pathway subsequent to the reaction catalyzed by beta-hydroxy-beta-methylglutaryl coenzyme A reductase (hydroxymethylglutaryl-CoA reductase, EC 1.1.1.34), the major regulatory enzyme of cholesterol biosynthesis. Changes in reductase activity can also affect the rate of dolichol synthesis. Since the majority of plasma glycoproteins are synthesized by the liver, we have measured the rate of dolichol synthesis in mouse-liver slices after various treatments which alter hepatic beta-hydroxy-beta-methyl-glutaryl-CoA reductase activity in vivo. The rate of hepatic dolichol synthesis was decreased by dietary cholesterol and fasting, and increased by feeding cholestyramine. There is also a diurnal variation in the rate of dolichol synthesis. A plot of the rate of dolichol synthesis versus the rate of cholesterol synthesis suggests that, after the formation of isoprene units, the branch of dolichol biosynthesis is saturated at a lower concentration of isoprene intermediates than is required to saturate the branch of cholesterol biosynthesis. After 2 weeks of cholesterol feeding and the consequent depression of hepatic dolichol synthesis, the rate of [3H]mannose incorporation into liver and plasma glycoproteins was unchanged, indicating that the rate of dolichol biosynthesis was not rate-limiting for total glycoprotein synthesis under these conditions.
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PMID:Regulation of hepatic dolichol synthesis by beta-hydroxy-beta-methylglutaryl coenzyme A reductase. 741 Mar 82

Opium and its derivatives are potent analgesics that can also induce severe side effects, including respiratory depression and addiction. Opioids exert their diverse physiological effects through specific membrane-bound receptors. Three major types of opioid receptors have been described, termed delta, kappa, and mu. The recent molecular cloning of these receptor types opens up the possibility to identify the ligand-binding domains of these receptors. To identify the ligand-binding domains of the kappa and delta receptors, we have expressed in COS-7 cells the cloned mouse delta and kappa receptors and chimeric delta/kappa and kappa/delta receptors in which the NH2 termini have been exchanged. The opioid antagonist naloxone binds potently to wild-type kappa receptor but not to wild-type delta receptor. The kappa/delta chimera bound [3H]naloxone with high affinity. In contrast, the kappa-specific agonist [3H]U-69,593 did not bind to the kappa/delta chimera. These findings indicate that selective agonists and antagonists interact with different recognition sites in the kappa receptor and localize the antagonist-binding domain to the NH2 terminus. Consistent with the results of radioligand-binding studies, the kappa/delta chimera did not mediate kappa-agonist inhibition of cAMP formation. In contrast, the delta/kappa chimera did mediate kappa-agonist inhibition of cAMP formation, but this effect was not blocked by naloxone. Furthermore, a truncated kappa receptor lacking its NH2 terminus was able to mediate agonist inhibition of cAMP accumulation in a naloxone-insensitive manner. This result further indicates that the NH2 terminus of the kappa receptor contains the selective antagonist-binding domain. The ability to dissociate agonist- and antagonist-binding sites will facilitate the development of more specific kappa agonists, which could have analgesic properties devoid of side effects.
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PMID:Agonists and antagonists bind to different domains of the cloned kappa opioid receptor. 805 54

Previously the plasma membrane-bound or purified Ca(2+)-translocation ATPase (Ca2+ pump) was found to be activated and phosphorylated by protein kinase C in vitro (K. K. W. Wang et al. 1991, J. Biol. Chem. 266, 9078-9085). We now show that in intact human erythrocytes phorbol-12-myristate 13-acetate (PMA), a known stimulator of protein kinase C, decreases the amplitude of the intracellular calcium ([Ca2+]i) transient induced by 2.5 microM CaCl2 and 10 microM A23187. Since PMA did not affect Ca2+ influx, the decrease in amplitude was most likely due to the stimulation of the Ca2+ pump, the major mechanism of calcium extrusion in these cells. The effect was dose-dependent, the maximum decrease in amplitude (33%) occurring at 1 microM PMA. The depression of the [Ca2+]i transient was further enhanced by the phosphatase inhibitor okadaic acid. It was reversed by the protein kinase C inhibitor staurosporine and could not be mimicked by inactive PMA analogues. In erythrocytes labeled with [32P]orthophosphate, PMA treatment phosphorylated the Ca(2+)-ATPase in a dose-dependent manner. The phosphorylation was inhibited by staurosporine and was slightly enhanced by okadaic acid. Changes in lipid phosphorylation and content were studied under the same conditions in intact cells. The turnover of 32P and lipid phosphate in phosphatidylinositol 4,5-bisphosphate (PIP2) was inhibited by 1 mM adriamycin, concomitant with an increased amplitude of the [Ca2+]i transient. The PIP2 content and its 32P radioactive did not, however, change with PMA stimulation. We conclude that while both protein kinase C and polyphosphoinositides are regulators of Ca(2+)-ATPase activity in the intact human erythrocyte, stimulation of the enzyme activity by PMA is predominantly protein kinase C-mediated.
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PMID:Regulation of the activity and phosphorylation of the plasma membrane Ca(2+)-ATPase by protein kinase C in intact human erythrocytes. 821 16

In 14 men and nine women referred because of severe primary hypertriglyceridemia, our specific aim in a 54-week single-blind treatment (Rx) period was to determine whether triglyceride (TG) lowering with a Type V diet and Lopid would lead to improvement in symptoms of depression, improvement in an index of life stressors, change in locus of control index, and improved cognition, as serially tested by Beck (BDI), Hassles (HAS) and HAS intensity indices, Locus of Control index, and the Folstein Mini-Mental status exam. On Rx, median TG fell 47%, total cholesterol (TC) fell 15%, and HDLC rose 19% (all p < or = 0.001). BDI fell at all nine Rx visits (p < or = 0.001), a major reduction in a test of depressive symptoms. The HAS score also fell at all nine visits (p < or = 0.05 - < or = 0.001). Comparing pre-Rx baseline BDI vs BDI at 30 and 54 weeks on Rx, there was a major shift towards absence or amelioration of depressive symptoms (chi 2= 5.9, p = 0.016). On Rx, the greater the percent reduction in TG, the greater the percent fall in BDI (r = 0.47, p < or = 0.05); the greater the percent reduction in TC, the greater the percent fall in HAS (r = 0.41, p < or = 0.05). Improvement in the BDI and HAS accompanied treatment of severe hypertriglyceridemia, possibly by virtue of improved cerebral perfusion and oxygenation. There may be a reversible causal relationship between high TG and symptoms of depression.
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PMID:Improvement in symptoms of depression and in an index of life stressors accompany treatment of severe hypertriglyceridemia. 839 21

We investigated the role of creatine kinase bound to sarcoplasmic reticulum membranes of fast skeletal muscle in the local regeneration of ATP and the possible physiological significance of this regeneration for calcium pump function. Our results indicate that ADP produced by sarcoplasmic reticulum Ca(2+)-ATPase is effectively phosphorylated by creatine kinase in the presence of creatine phosphate. This phosphorylation is an important function of the membrane-bound creatine kinase because accumulation of ADP has a depressive effect on Ca(2+)-uptake by sarcoplasmic reticulum vesicles. The concentration-dependent depression of Ca(2+)-uptake by ADP was especially pronounced when there was strong back inhibition by high intravesicular [Ca2+]. ATP regenerated by endogenous creatine kinase was not in free equilibrium with the ATP in the surrounding medium, but was used preferentially by Ca(2+)-ATPase for Ca(2+)-uptake. Efficient translocation of ATP from creatine kinase to Ca(2+)-ATPase, despite the presence of an ATP trap in the surrounding medium, can be explained by close localization of creatine kinase and Ca(2+)-ATPase on the sarcoplasmic reticulum membranes. These results suggest the existence of functional coupling between creatine kinase and Ca(2+)-ATPase on skeletal muscle sarcoplasmic reticulum membranes. Several factors (amount of membrane-bound creatine kinase, oxidation of SH groups of creatine kinase, decrease in [phosphocreatine]) can influence the ability of creatine kinase/phosphocreatine system to support a low ADP/ATP ratio and fuel the Ca(2+)-pump with ATP. These factors may become operative in the living cells, influencing functional coupling between creatine kinase and Ca(2+)-ATPase and may have an indirect effect on Ca(2+)-pump function before Ca(2+)-ATPase itself is affected.
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PMID:Functional coupling between sarcoplasmic-reticulum-bound creatine kinase and Ca(2+)-ATPase. 850 36

The effect of cisplatin and the new drug cycloplatam (amine (cyclopentylamine)-S-(-)-malatoplatinum (II)) on protein kinase C (PKC) activity and Ca(2+)-dependent binding of PKC to T lymphocytes membranes was studied in vivo and in vitro. At first, the effect of the drugs on PKC activity of intact and activated lymphocytes was studied in vivo. In 48 hours after intraperitoneal injection of mice with therapeutic doses of the drugs, PKC activity of intact lymphocytes was differentially affected. Cisplatin did not practically alter the enzyme activity, whereas cycloplatam inhibited the PKC activity by 37% versus control. In lymphocytes activated by mouse P-388 leukemia cells in vivo, the drugs caused almost complete suppression of PKC activity and Ca(2+)-dependent binding of the enzyme to the membranes. The drugs were effective in intact cells. After incubation of intact lymphocytes in vitro for 24 hours with cisplatin or cycloplatam (10(-5)M), PKC activity was increased 1.62- and 1.35-fold, respectively, versus control. Ca(2+)-dependent binding of the enzyme to the membranes was also increased 1.61- and 1.36-fold by cisplatin and cycloplatam, respectively. On the contrary, at 10(-4) M concentration under similar conditions, the drugs did not affect the PKC activity of the lymphocytes. Furthermore, cycloplatam, unlike cisplatin, reduced the PKC binding to cellular membranes by 31%. The mechanisms of the drugs effects on PKC activity are suggested. The data indicate that increase or decrease of PKC activity induced by the drugs cause stimulation or depression of functional activity of T lymphocytes, respectively. Thus, the membrane-bound PKC can play the key role in initiation and development of immunomodulatory effects of cisplatin and cycloplatam.
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PMID:[Effect of anti-tumor agents cisplatin and cycloplatam on membrane protein kinase C activity in murine T-lymphocytes]. 901 Dec 34

Protein kinase C was purified to homogeneity from liver of the anoxia-tolerant turtle (Trachemys scripta elegans). Two isozymes were present and were identified as PKC alpha and PKC beta by hydroxylapatite chromatography and cross-reaction with specific antibodies to the mammalian isozymes. Kinetic characterization of the isozymes showed that both required phospholipids and Ca2+ for activation and both were inhibited by low concentrations of PKC inhibitors. The PKC alpha was activated more strongly by phosphatidylinositol and lysophosphatidylinositol compared with PKC beta. Treatment with trypsin did not activate turtle PKC isozymes, but generated inactive PKC beta, whereas PKC alpha was resistant to inactivation. Anoxia exposure of turtles in vivo, via submergence in N2-gassed water at 7 degrees C, altered the activity and subcellular distribution of PKC in liver. After 1 hr of anoxic exposure at 7 degrees C, the activity of membrane-bound PKC had increased by 2.4-fold and represented a translocation of 40% of PKC beta and more than 80% of PKC alpha from the cytosol to the membrane-associated fraction. With longer submergence, however, membrane-bound PKC activity was suppressed again. This two-phase response to anoxia by PKC suggests that an activation of PKC, through its translocation to the membrane, is important in mediating the initial metabolic responses to submergence, which include an activation of glycogenolysis during the hypoxia transition period. With sustained anoxia exposure, the subsequent reduction of PKC activity may be part of the overall mechanism of metabolic rate depression that allows endurance of prolonged anoxia.
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PMID:Liver protein kinase C isozymes: properties and enzyme role in a vertebrate facultative anaerobe. 902 85

Diabetes mellitus is associated with alterations in lipid metabolism and cardiac dysfunction despite an absence of coronary arteriosclerotic changes. To investigate mechanisms of cardiac dysfunction in diabetic cardiomyopathy, we studied the relation between activities of membrane-bound enzymes and surrounding phospholipids in rats with diabetes induced with a single intravenous injection of streptozotocin (65 mg/kg). We found that total phospholipid content of sarcoplasmic reticulum membrane increased significantly 8 weeks after treatment with streptozotocin owing to increases in phosphatidylcholine and phosphatidylethanolamine, a decrease in arachidonic acid, and an increase in docosahexaenoic acid in the early stage of diabetes. Sarcolemmal Na+/K(+)-ATPase activity and the number of receptors decreased in isolated cardiomyocytes of diabetic rats 8 weeks after streptozotocin administration. The Ca2+ uptake of both sarcoplasmic reticulum and mitochondria decreased simultaneously in permeabilized, isolated cardiomyocytes from diabetic rats. The depression of membrane-bound enzyme activities was correlated with alterations in phospholipids, which are closely related to the microenvironment of membrane-bound enzymes and influence intracellular Ca2+ metabolism. Because these changes in phospholipids and fatty acids were reversible with insulin therapy, they are diabetes-specific and might be a cause of cardiac dysfunction in diabetes.
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PMID:Changes in microsomal membrane phospholipids and fatty acids and in activities of membrane-bound enzyme in diabetic rat heart. 934 28

Retrograde signaling from the postsynaptic cell to the presynaptic neuron is essential for the development, maintenance, and activity-dependent modification of synaptic connections. This review covers various forms of retrograde interactions at developing and mature synapses. First, we discuss evidence for early retrograde inductive events during synaptogenesis and how maturation of presynaptic structure and function is affected by signals from the postsynaptic cell. Second, we review the evidence that retrograde interactions are involved in activity-dependent synapse competition and elimination in developing nervous systems and in long-term potentiation and depression at mature synapses. Third, we review evidence for various forms of retrograde signaling via membrane-permeant factors, secreted factors, and membrane-bound factors. Finally, we discuss the evidence and physiological implications of the long-range propagation of retrograde signals to the cell body and other parts of the presynaptic neuron.
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PMID:Retrograde signaling in the development and modification of synapses. 945 71


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