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)

Using two-dimensional gel electrophoresis, we have analyzed the polypeptide alteration of the human myeloid leukemia cell line HL60 during differentiation induced by dimethylsulfoxide (DMSO) and 12-0-tetradecanoylphorbol-13-acetate (TPA). Three polypeptides increased in synthesis after DMSO treatment, while 5 polypeptides increased after TPA treatment. Most other polypeptides were synthesized at a reduced rate though their net amounts remained unchanged, indicating that myeloid differentiation was associated not only with an increased synthesis of a few specific polypeptides but also with overall depression of most other polypeptides. One of the early differentiation marker proteins (mol. wt. approx. 20,000, pI approx. 6.0) of granulopoietic cells was increased specifically after DMSO treatment, while one of the monocyte specific marker proteins (mol. wt approx. 46,000, pI approx. 4.8) was detected after TPA treatment. But, the pattern of HL60 cells did not necessarily become similar to that of normal mature granulocytes after DMSO treatment, indicating that HL60 cell differentiation might be partial or incomplete.
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PMID:Alteration of polypeptide synthesis and composition during differentiation of human leukemia cell line HL60. 659 81

The incorporation of radioactivity into HeLa cell polypeptides and DNA after exposure to 45 degrees C heating for 15 min was measured by continuous exposure to radiolabeled precursors. Both polypeptide and DNA synthesis were inhibited by thermal shock. The rate of incorporation of radiolabeled amino acids into whole cell, nuclear, or histone protein recovered to control levels by 5 to 8 hr after thermal shock. The rate of incorporation of radiolabeled thymidine into DNA did not recover to a control level within the first 8 hr after thermal shock. Thermal effects on amino acid and nucleotide precursor pools could not explain the inhibition of either protein or DNA synthesis. Since histone protein synthesis recovers prior to DNA synthesis, we conclude that the inhibition of histone protein synthesis after thermal shock is not responsible for the depression in synthesis of cellular DNA.
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PMID:Macromolecule synthesis in HeLa cells after thermal shock. 665 29

Comparison of three different lines of bovine aortal endothelial cells provides a clear demonstration of reversible morphologic phenotype coincidental with change in expression and growth mode. These phenotypic forms can be externally controlled so that cells may exist either in an epithelioid contact-inhibitable state or as a fibroblastoid non-contact-inhibitable state. Clonal cell line N (normal) shows a strong tendency to maintain the epithelioid phenotype. Clonal cell line Sp (sprout) can readily and reversibly adopt the epithelioid or fibroblastoid phenotype. A factor in normal serum is responsible for maintaining the cells in the epithelioid phenotype. This factor could be a growth factor since several polypeptide growth factors are shown to drive cells from the fibroblastoid phenotype to the epithelioid phenotype within 11 hours. This growth factor-induced change is not mediated through induced DNA synthesis. Clonal cell line V (variant) normally maintains the fibroblastoid phenotype but can be directed to the epithelioid phenotype provided cells are on an appropriate collagenous matrix. Associated with these changes in morphological phenotype are depression of the expression of the pro alpha 2 chain of collagen type I which may be characteristic of the contact-inhibited state and of an 80,000 mol wt polypeptide synthesized only by cells in the fibroblastoid phenotype. An endothelial cell collagen EC1 (mol wt 177,000) was synthesized by all cell lines regardless of phenotype whereas a suspected breakdown product EC3 (mol wt 100,000) was found only in the epithelioid phenotype. Other differences and similarities between cell lines include expression of a 135,000 mol wt glycoprotein GP (V and N), the procollagen of collagen type III (N) of fibronectin (N, V, Sp), and of the pro alpha 1 chain of collagen type I (Sp, V). The characteristic expression of each line and its response to signals controlling morphologic phenotype impinges on the question of whether there exist several distinct types of vascular endothelial cells with different functional potentials controlled by extracellular signals.
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PMID:Signals causing change in morphological phenotype, growth mode, and gene expression of vascular endothelial cells. 710 19

The interaction of melittin, a polypeptide consisting of 26 amino acid residues, with dimyristoyl phosphatidylcholine bilayers was investigated by vibrational Raman spectroscopy. Spectral peak height intensity ratios, involving vibrational transitions in both the 3000 cm-1 acyl chain methylene carbon-hydrogen stretching mode region and the 1100 cm-1 acyl chain carbon-carbon skeletal stretching mode interval, served as temperature profile indices for monitoring the bilayer order-disorder processes. For a lipid : melittin molar ratio of 14 : 1 two order-disorder transitions were observed. In comparison to a gel to liquid crystalline phase transition of 22.5 degrees C for the pure lipid, the lower transition, exhibiting a 2 degree C width, is centered at 17 degrees C and is associated with a depression of the main lipid phase transition of dimyristoyl phosphatidylcholine. The second thermal transition, displaying a 7 degree C interval, occurs at approx. 29 degrees C and is associated with the melting behavior of approximately seven immobilized boundary lipids which surround the inserted hydrophobic segment of the polypeptide. For a lipid : melittin molar ratio of 10 : 1 two thermal transitions are also observed at 11 and 30 degrees C. As before, they represent, respectively, the main gel to liquid crystalline phase transition and the melting behavior of approximately four boundary lipids attached to melittin. From these data alternative schemes are suggested for disposing the immobilized lipids around the hydrophobic portion of the polypeptide within the bilayer.
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PMID:Interaction of melittin with dimyristoyl phosphatidylcholine liposomes: evidence for boundary lipid by Raman spectroscopy. 739 74

C2 domains are regulatory sequence motifs that occur widely in nature. Synaptotagmin I, a synaptic vesicle protein involved in the Ca2+ regulation of exocytosis, contains two C2 domains, the first of which acts as a Ca2+ sensor. We now describe the three-dimensional structure of this C2 domain at 1.9 A resolution in both the Ca(2+)-bound and Ca(2+)-free forms. The C2 polypeptide forms an eight-stranded beta sandwich constructed around a conserved four-stranded motif designated as a C2 key. Ca2+ binds in a cup-shaped depression between two polypeptide loops located at the N- and C-termini of the C2-key motif.
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PMID:Structure of the first C2 domain of synaptotagmin I: a novel Ca2+/phospholipid-binding fold. 769 23

Roles for ubiquitin (an 8.5 kDa polypeptide) involve its conjugation to proteins as a signal to initiate degradation and as a stress protein. We investigated ubiquitin conjugation and ubiquitin-dependent proteolytic activities in cultured bovine lens epithelial cells (BLECs) upon oxidative challenge. A 44% decrease in intracellular glutathione confirmed oxidative stress upon incubation with 1 mM H2O2. After 30 min incubation, endogenous high-molecular-mass ubiquitin conjugates decreased 73%, and intracellular proteolysis decreased about 50%. In the supernatants of the oxidatively treated BLECs, the ability to form high-molecular-mass ubiquitin conjugates with exogenous 125I-labelled ubiquitin decreased 28%, and ATP-dependent degradation of oxidized alpha-crystallin decreased 36%. When the H2O2-treated BLECs were allowed to recover for 60 min, intracellular proteolysis returned to the level of control cells. There was also a subsequent transient enhancement of intracellular proteolysis and a simultaneous recovery of endogenous high-molecular-mass ubiquitin conjugates. In parallel cell-free experiments, conjugating activity with exogenous 125I-labelled ubiquitin and ATP-dependent degradation of oxidized alpha-crystallin increased 35% and 72% respectively compared with non-oxidatively treated BLECs. ATP-independent proteolysis showed little response to exposure or removal of H2O2. These results indicate that (1) the rate of intracellular proteolysis in BLECs is associated with the level of endogenous high-molecular-mass ubiquitin conjugates and (2) oxidative stress may inactivate the ubiquitin conjugation activity with coordinate depression of proteolytic capability. Enhancement in ubiquitin conjugation and proteolytic activities during recovery from oxidative stress may be important in removal of damaged proteins and restoration of normal function of BLECs. The inactivation of ubiquitin-dependent proteolysis by oxidation may be involved in the accumulation of altered proteins and other adverse sequelae in the oxidatively challenged aging lens.
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PMID:Oxidative stress and recovery from oxidative stress are associated with altered ubiquitin conjugating and proteolytic activities in bovine lens epithelial cells. 771 89

The large ribosomal subunit of the thermophilic fungus Thermomyces lanuginosus was treated with 2.96 M NH4Cl to remove specific complements of ribosomal proteins, and the core particles thereby derived were imaged by bright field transmission electron microscopy, and recurring views computed by single particle electron image analysis. A new characteristic projection was elucidated which showed a large depression or channel passing through the subunit. Such a channel has been perceived in the prokaryotic large ribosomal subunit under certain conditions and has been postulated to be the exit pathway for the nascent polypeptide chain, but its existence has not hitherto been demonstrated in eukaryotes.
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PMID:Does the eukaryotic large ribosomal subunit have a channel passing through it? 781 Dec 76

Several analogs of an alanine-rich alpha-helical antifreeze polypeptide were synthesized and studied to evaluate the role of charged amino acids on structure and activity. alpha-Helix content and thermal stability were assessed by circular dichroism spectrometry and antifreeze activity by freezing point depression (thermal hysteresis) and ice crystal growth rate measurements. Rearrangement, deletion and replacement of charged amino acids resulted in reduced helicity and antifreeze activity in some cases, but the effects were not dramatic. We conclude that the i+4 ion pair Lys18/Glu22 helps to stabilize the alpha-helix but is not absolutely essential for activity. NH2-terminal Asp does not contribute significantly to helix stability or activity, but the COOH terminus is sensitive to modification, since replacement of Arg37 can lead to reduced helix content and activity. In general, factors which reduce alpha-helix content also reduce antifreeze activity.
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PMID:Structure-function relationships in an antifreeze polypeptide. The role of charged amino acids. 834 24

Acetohydroxy acid synthase (AHAS, EC 4.1.3.18) catalyzes the thiamin pyrophosphate (TPP)-dependent decarboxylation of pyruvate and condensation of the resulting two-carbon moiety with a second alpha-keto acid. It belongs to a family of homologous, TPP-dependent enzymes which catalyze different reactions which start from decarboxylation of alpha-keto acids. A model for the structure of Escherichia coli AHAS isozyme II, based on its homology with pyruvate oxidase and experimental testing of the model by site-directed mutagenesis, has been used here to study how AHAS controls the chemical fate of a decarboxylated keto acid. Because of the potential conformational freedom of the reacting substrates, residues interacting with the substrate could not be identified directly from the model of AHAS. Three residues were considered as candidates for involvement in the recognition of alpha-ketobutyrate, as the amino acids at these sites in a unique low-specificity AHAS are different from those in typical AHASs, which are highly specific for reaction with alpha-ketobutyrate as second substrate, in preference to pyruvate. These residues were altered in AHAS II by site-directed mutagenesis. Replacement of Trp464 lowers the specificity by at least 1 order of magnitude, with minor effects on the activity or stability of the enzyme, suggesting that Trp464 contributes > or = 1.3 kcal mol-1 to interaction with the "extra" methyl of alpha-ketobutyrate. Mutations of Met460 or Thr70 have small effects on specificity and do affect other properties of the protein. A model for enzyme-substrate interactions can be proposed on the basis of these results. The model of AHAS also explains previously reported spontaneous mutants of AHAS resistant to sulfonylurea herbicides, which probably bind in the narrow depression which provides access to the bound TPP. A role for the C terminus of the enzyme polypeptide in determination on the reaction pathway is also possible.
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PMID:Homology modeling of the structure of bacterial acetohydroxy acid synthase and examination of the active site by site-directed mutagenesis. 897 2

The efficacy of aprotinin to reduce intraoperative bleeding tendency in cardiac operations has been demonstrated in several studies. Aprotinin is a polybasic polypeptide and has antigenic properties. Anaphylactic reactions to aprotinin have been described. The aim of the present study was to evaluate the prevalence of adverse reactions to reexposure to high-dose aprotinin. The clinical outcome of all patients undergoing heart operations in our institution between 1988 and 1995 with at least two exposures to aprotinin was investigated. There were 248 reexposures to aprotinin in 240 patients: 101 adult and 147 pediatric cases. The total aprotinin doses were 4.9 x 10(6) (interquartile range 2 x 10(6)) KIU (adults) and 1.3 x 10(6) (interquartile range 1.2 x 10(6)) KIU (pediatric patients). The time between the first and second aprotinin exposures was 344 (interquartile range 1039) days. Seven adverse reactions to aprotinin were found (2.8%). The severity of the reaction ranged from mild (no intervention) to severe (longer-lasting circulatory depression despite vasopressor therapy). All patients survived the event. Patients with an interval less than 6 months since the previous exposure had a statistically higher incidence of adverse reactions than patients with a longer interval (5/111 or 4.5% vs 2/137 or 1.5%, p < 0.05). Two patients reacted to a test dose of 10,000 KIU aprotinin. Pretreatment with antihistaminics was done in 60% of the patients. We recommend the following procedure for reexposure with high-dose aprotinin: (1) delay of the first bolus injection of aprotinin until the surgeon is ready to begin cardiopulmonary bypass, (2) test dose of 10,000 KIU aprotinin in all patients with aprotinin treatment, (3) H1/H2 blockade in known or possible reexposures, and (4) avoidance of reexposure within the first 6 months after the previous exposure to aprotinin. With these precautions a reexposure to aprotinin in patients with a high risk of bleeding is justified, because the benefits of aprotinin treatment outweigh the relative risk of a serious allergic reaction.
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PMID:Prevalence of anaphylactic reactions to aprotinin: analysis of two hundred forty-eight reexposures to aprotinin in heart operations. 901 90


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