Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0009443 (cold)
 92,137 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The isolated working rat heart model was use to define the cardioprotective effects (function, metabolic and ultrastructure) of the oxygenated St. Thomas' Hospital No. 2 cardioplegic solution (STH) during lengthy, hypothermic ischaemia (20 degrees C, 4 hours and 5 hours). Hearts (n = 9 for each group) were arrested with and exposed to multidose reinfusion (2 min every 40 min interval) throughout the ischaemic period with the cold (4 degrees C) STH or oxygenated (95% O2:5% CO2) STH. Oxygenated STH significantly (p < 0.01) improved the postischaemic recovery of cardiac output from 49.5 +/- 11.1% to 96.8 +/- 1.5% (in 4 hours) and from 20.3 +/- 7.2% to 72.2 +/- 5% (in 5 hours). Other indices of functional recovery showed similar improved performance with the significant decrease in time from the onset of reperfusion to the return of regular sinus rhythm (57 +/- 8 v 495 +/- 150 s). The efflux of lactate during 5 hr ischaemic arrest was decreased (20.62 +/- 1.3 v 26.18 +/- 1.73 mumol/heart for oxygenated STH and STH, respectively, p < 0.05) and the progressive increase in the coronary vascular resistance was abolished in the oxygenated STH treated hearts. These improvements were associated with the reduction in the decline of the myocardial adenosine triphosphate (14.49 +/- 2 v 3.3 +/- 0.19 mumol/g dry wt), creatine phosphate (24.61 +/- 3.47 v 7.48 +/- 1.34 mumol/g dry wt) and guanosine triphosphate (1.69 +/- 0.2 v 0.84 +/- 0.08 mumol/g dry wt) during ischaemia, total resynthesis after reperfusion (ATP: 103% v 36%, CP: 105% v 69% and GTP: 203% v 61% of control) and the total absence of myocardial cells and microvasculature injuries in ischaemic (non-reperfused) hearts. These results confirm that the provision of additional oxygen to the St. Thomas' Hospital solution (with 95% O2:5% CO2) can meet the metabolic demand of the ischaemic myocardium and thus increase the safe duration of cardiac arrest.
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PMID:Protective effects of oxygenated St. Thomas' Hospital cardioplegic solution during ischaemic cardiac arrest: improved function, metabolism and ultrastructure. 828 49

Similar cold-sensitive properties, values of dissociation constants (Kd = 1 x 10(-10) M), and regulatory effectors were found for the cold-sensitive cytosolic 3,5,3'-triiodo-L-thyronine (L-T3)-binding protein (CTBP) and pyruvate kinase from human erythrocyte. Various metabolites of the blood cell were assayed for their effects on CTBP activity after heat and cold preincubation treatments. Among these compounds, five- and six-carbon phosphorylated sugars were effective in protecting the CTBP activity against cold inactivation, whereas only ATP and dATP blocked activation by heat treatments. The effects of fructose 1,6-bisphosphate, fructose 2,6-bisphosphate, and ATP were obtained at physiological concentrations. Three-carbon phosphorylated intermediates of glycolysis, ADP, AMP, cAMP, and GTP had no effect on cold and heat treatments. The monomer-tetramer interconversion of the enzyme was also regulated by fructose 1,6-bisphosphate and ATP. The association is under the control of fructose 1,6-bisphosphate, whereas the dissociation is under ATP control. This regulation may have physiological relevance since the hormone binds to the tetrameric form of the enzyme at a site other than the active site.
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PMID:Cold-sensitive cytosolic 3,5,3'-triiodo-L-thyronine-binding protein and pyruvate kinase from human erythrocytes share similar regulatory properties of hormone binding by glycolytic intermediates. 841 25

Microtubule assembly was examined in the high-speed supernatant from homogenates of young (2-4 months old) and old (more than 24 months old) rat brains and significant age-related differences in microtubule assembly were found in the absence of exogenous GTP. In extracts from young brains, the increase in absorbance at 350 nm, which reflects the assembly reaction, was characterized by three phases (lag, elongation, and steady state) superimposed on a slow continuous increase due to non-specific aggregation. However, assembly in extracts from old brains, was very sluggish, in some cases barely more rapid than the non-specific aggregation reaction. Two to three times as much protein was assembled into cold-labile microtubules in extracts from young brains than from old brains. When 1 mM GTP was included in the assembly solutions the patterns of assembly in extracts from young and old brains became similar, with about the same amount of protein assembled into cold-labile microtubules. The assembly of tubulin purified from rat brains showed no differences between young and old. Results showed that extracts from old brains contained a higher GTPase activity than extracts from young brains. The sluggish assembly in extracts from old brains could be due to a deficiency in GTP or an inefficient regeneration of GTP.
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PMID:A comparison of microtubule assembly in brain extracts from young and old rats. 847 79

2-Methoxyestradiol (2ME) is an endogenous mammalian catabolite of estradiol with antimitotic activity. Although it is a competitive inhibitor of the binding of colchicine to tubulin, it has unusual effects on glutamate-induced tubulin polymerization. Polymer that was little changed in morphology assembled at a reduced rate and was relatively cold stable. We have now examined interactions of [4-3H]-2ME with unpolymerized tubulin and polymer. The [3H]2ME binds avidly to tubulin even on ice, and it is readily displaced by other colchicine site drugs. An association rate constant on ice of 1.9 x 10(2) M-1s-1 was obtained. Scatchard analysis indicated a single class of binding site and an association equilibrium constant of 5.7 x 10(5) M-1. These values lead to a calculated dissociation rate constant of 3.3 x 10(-4) s-1. In glutamate-induced tubulin assembly, a reaction that requires GTP and leads to the formation of sheets of parallel protofilaments, increasing amounts of [3H]2ME were incorporated into polymer, reaching near-stoichiometry with tubulin at 100 microM 2ME. Equivalent binding of [3H]2ME occurred when the drug was added to preformed polymer, but binding of [3H]2ME to polymer was not readily inhibited by colchicine site drugs. Significant amounts of [3H]2ME were also incorporated into microtubule polymer formed with microtubule-associated proteins, glycerol, or 4-morpholineethanesulfonate buffer, but the stoichiometry was substantially lower than that in the sheet polymer induced by either glutamate or 1,4-piperazineethanesulfonate buffer. The structural differences between the microtubule and sheet polymers leading to these differences in apparent affinity for 2ME are unknown, but presumably interaction of the estrogen metabolite with cellular microtubules has functional significance related to the antimitotic properties of the compound.
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PMID:Interactions of 2-methoxyestradiol, an endogenous mammalian metabolite, with unpolymerized tubulin and with tubulin polymers. 857 87

Translation elongation factor 1beta (EF-1beta) catalyzes the exchange of bound GDP for GTP on EF-1alpha. The lethality of a null allele of the TEF5 gene encoding EF-1beta in Saccharomyces cerevisiae was suppressed by extra copies of the TEF2 gene encoding EF-1alpha. The strains with tef5::TRP1 suppressed by extra copies of TEF were slow growing, cold sensitive, hypersensitive to inhibitors of translation elongation and showed increased phenotypic suppression of +1 frameshift and UAG nonsense mutations. Nine dominant mutant alleles of TEF2 that cause increased suppression of frameshift mutations also suppressed the lethality of tef5::TRP1. Most of the strains in which tef5::TRP1 is suppressed by dominant mutant alleles of TEF2 grew more slowly and were more antibiotic sensitive than strains with tef5::TRP1 is suppressed by wild-type TEF2. Two alleles, TEF2-4 and TEF2-10, interact with tef5::TRP1 to produce strains that showed doubling times similar to tef5::TRP1 strains containing extra copies of wild-type TEF2. These strains were less cold sensitive, drug sensitive and correspondingly less efficient suppressor of +1 frameshift mutations. These phenotypes indicate that translation and cell growth are highly sensitive to changes in EF-1alpha and EF-1beta activity.
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PMID:Increased expression of Saccharomyces cerevisiae translation elongation factor 1 alpha bypasses the lethality of a TEF5 null allele encoding elongation factor 1 beta. 864 86

LTE1 encodes a homolog of GDP-GTP exchange factors for the Ras superfamily and is required at low temperatures for cell cycle progression at the stage of the termination of M phase in Saccharomyces cerevisiae. We isolated extragenic suppressors which suppress the cold sensitivity of lte1 cells and confer a temperature-sensitive phenotype on cells. Cells mutant for the suppressor alone were arrested at telophase at non-permissive temperatures and the terminal phenotype was almost identical to that of lte1 cells at non-permissive temperatures. Genetic analysis revealed that the suppressor is allelic to CDC15, which encodes a protein kinase. The cdc15 mutations thus isolated were recessive with regard to the temperature-sensitive phenotype and were dominant with respect to suppression of lte1. We isolated CDC14 as a low-copy-number suppressor of cdc15-rlt1. CDC14 encodes a phosphotyrosine phosphatase (PTPase) and is essential for termination of M phase. An extra copy of CDC14 suppressed the temperature sensitivity of cdc15-rlt1 cells, but not that of cdc15-1 cells. In addition, some residues that are essential for the CDC14 PTPase activity were found to be non-essential for the suppression. These results strongly indicate that Cdc14 possesses dual functions; PTPase activity is needed for one function but not for the other. We postulate that the cooperative action of Cdc14 and Cdc15 plays an essential role in the termination of M phase.
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PMID:Dominant mutant alleles of yeast protein kinase gene CDC15 suppress the lte1 defect in termination of M phase and genetically interact with CDC14. 866 28

The RHO1 gene encodes a homolog of the mammalian RhoA small GTP-binding protein in the yeast Saccharomyces cerevisiae. Rho1p is localized at the growth site and is required for bud formation. The RHO1(G22S, D125N) mutation is a temperature-sensitive and dominant negative mutation of RHO1, and a multicopy suppressor of RHO1(G22S, D125N), ROM7, was isolated. Nucleotide sequencing of ROM7 revealed that it is identical to the BEM4 gene (GenBank accession number L27816), although its physiological function has not yet been reported. Disruption of BEM4 resulted in the cold- and temperature-sensitive growth phenotypes, and cells of the deltabem4 mutant showed abnormal morphology, suggesting that BEM4 is involved in the budding process. The temperature-sensitive growth phenotype was suppressed by overexpression of RHO1, ROM2, which encodes a Rho1p-specific GDP/GTP exchange factor, or PKC1, which encodes a target of Rho1p. Moreover, glucan synthase activity, which is activated by Rho1p, was significantly reduced in the deltabem4 mutant. Two-hybrid and biochemical experiments revealed that Bem4p directly interacts with the nucleotide-free form of Rho1p and, to lesser extents, with the GDP- and GTP-bound forms of Rho1p, although Bem4p showed neither GDP/GTP exchange factor, GDP dissociation inhibitor, nor GTPase-activating protein activity toward Rho1p. These results indicate that Bem4p is a novel protein directly interacting with Rho1p and is involved in the RHO1-mediated signaling pathway.
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PMID:ROM7/BEM4 encodes a novel protein that interacts with the Rho1p small GTP-binding protein in Saccharomyces cerevisiae. 875 40

Trypomastigotes of Trypanosoma cruzi were impermeable to exogenous radiolabeled ATP for up to 2 h at 4 degrees C. Radioligand binding assays in the cold showed that trypomastigotes had two populations of saturable ATP receptors (ATP-Rs) and the radioligand interaction was reversed by nonlabeled ATP in concentration-dependent assays. The Kds of high- and low-affinity ATP-Rs were 7.27 x 10(-8) and 4.32 x 10(6)M, respectively. The BmaxS for ATP-R1 and ATP-R2 were 2.05 x 10(-14) and 2.50 x 10(-12) mol/4 x 10(-6) flagellates, respectively, or 3100 ATP-R1 copies per trypomastigote and 376,000 ATP-R2 copies per trypomastigote. ATP,2-methyl-thio-ATP,ITP, and ADP displaced ATP-Rs (IC50s: 2.59 x 10(-6) to 7.84 x 10(-6)M/4 x 10(6) trypomastigotes). UTP, CTP, ADP beta S, Cibacron blue, and azido-ATP were 10-100 times less effective. Atractyloside, adenosine, suramin, cAMP, Basilen blue, and GTP failed to displace T. cruzi ATP-Rs. Infective vertebrate stage trypomastigote ATP-Rs were localized to a family of 63 kDa surface glycopolypeptides and ATP-Rs appeared to be stage-regulated because the noninfective insect epimastigote forms had ATP-Rs with KdS that are not capable of metabolic interactions with host-cell micromolar ATP levels. Trypomastigote ATP-Rs may play an important role in the induction of the process of T. cruzi intracellular parasitosis.
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PMID:Plasma membrane ATP receptors in Trypanosoma cruzi trypomastigotes. 884 Mar 98

We have previously described the rat liver resealed nuclear envelope model system for the study of the selective import of nuclear proteins, and the export of poly(A)-containing mRNA [Riedel, N., Bachmann, M., Richter, H. & Fasold, H. (1987) Proc. Natl Acad. Sci. USA 83, 3540-3544]. The vesicles still respond to the importin-ATP signal for the uptake of nuclear-location-sequence (NLS)-carrying proteins. During the preparation of the vesicles and extraction of the chromatin from nuclei in cold hypotonic heparin solution, ribosomal subunits may be introduced into these envelopes, and after resealing remain stably included. Efflux from the resealed nuclear envelopes is effected by a cytoplasmatic protein fraction, and strongly enhanced in the presence of ATP. The heterogeneous nuclear RNP (hnRNP) A1, the components of importin, or GTP showed no influence on this export. The ATP-dependent efflux of mRNA is not affected by these cytoplasmic proteins in this model system.
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PMID:Export of ribosomal subunits from resealed rat liver nuclear envelopes. 889 85

A protein kinase which phosphorylates in vitro the biosynthetic ornithine decarboxylase (ODC) was partially purified from Escherichia coli. In vivo phosphorylation of ODC occurs after incubation of E. coli with [32P]orthophosphate. When the recombinant ODC was incubated with calf intestine alkaline phosphatase it was inactivated and this inactive ODC could be reversibly activated allosterically only by guanyl or uracyl phosphate analogues at a concentration of 10(-4) or 10(-3) M. The pH optimum of the [8-3H]GTP binding was determined and it was shown that the GTP binding is proportional to the amount of ODC. The [8-3H]GTP binds specifically to ODC as was proved by the addition of cold GTP or ATP. High concentration of GTP can dissociate the ODC-antizyme complex and either reactivate or liberate the ODC. Therefore, a working hypothesis is suggested describing the regulation of ODC by phosphorylation-dephosphorylation reaction or by antizyme and nucleotide analogues interaction.
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PMID:Regulation of the Escherichia coli biosynthetic ornithine decarboxylase activity by phosphorylation and nucleotides. 891 26


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