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

Previous work from our laboratory demonstrated that exposing rats to cold increases interscapular brown adipose tissue (IBAT) adenylate cyclase activity through a postreceptor modification of the adenylate cyclase system. The cold-induced sensitization is correlated with an increase in the activity of the sympathetic innervation of IBAT, and is prevented by prior surgical denervation of this tissue. The present experiments were aimed at identifying the neurogenic signal that mediates cold-induced sensitization. We found that, like cold exposure, infusions of norepinephrine increased adenylate cyclase activity and enhanced the ability of cholera toxin to ADP-ribosylate the stimulatory regulatory protein of adenylate cyclase (Gs) in warm-adapted rats whose IBAT had been denervated surgically. Infusions of isoproterenol increased adenylate cyclase responsiveness more potently than norepinephrine; however, the maximal effect achieved by isoproterenol was less than that produced by norepinephrine. Infusions of phenylephrine and clonidine had no effect on adenylate cyclase responsiveness. The effects of low doses of isoproterenol, however, were greatly potentiated by coinfusion of phenylephrine. Furthermore, the sensitizing effects of norepinephrine could be blocked by either propranolol or prazosin, indicating that the effects of norepinephrine require simultaneous stimulation of beta and alpha-1 adrenergic receptors.
 ...
PMID:Norepinephrine infusions increase adenylate cyclase responsiveness in brown adipose tissue. 283 2

The effects of chlorpromazine on various properties of the F1-ATPases from bovine heart mitochondria (MF1), the plasma membranes of Escherichia coli (EF1), and plasma membranes of the thermophilic bacterium PS3 (TF1) have been examined. While chlorpromazine inhibited MF1 with an I0.5 of about 50 microM and EF1 with an I0.5 of about 150 microM at 23 degrees C, the ATPase activity of TF1 was stimulated by chlorpromazine concentrations up to 0.6 mM at this temperature. Maximal activation of about 20% was observed at 0.2 mM chlorpromazine at 23 degrees C. Chlorpromazine concentrations greater than 0.6 mM inhibited TF1 at 23 degrees C. At 37 degrees C the ATPase activity of TF1 was doubled in the presence of 0.5 mM chlorpromazine, the concentration at which maximal stimulation was observed at this temperature. Chlorpromazine inhibited the rate of inactivation of EF1 by dicyclohexylcarbodiimide (DCCD) at 23 degrees C and pH 6.5. Concentrations of chlorpromazine which inhibited the ATPase activity of TF1 at pH 7.0 accelerated the rate of inactivation of the enzyme by DCCD at pH 6.5, while lower concentrations of the phenothiazine, which stimulated the ATPase, had no effect on DCCD inactivation. Chlorpromazine concentrations up to 1.0 mM had no effect on the rate of inactivation of TF1 by DCCD at 37 degrees C and pH 6.5. Chlorpromazine at 0.5 mM accelerated the rate of inactivation of MF1 by 5'-p-fluorosulfonylbenzoyladenosine (FSBA), while it slowed the rate of inactivation of EF1 by FSBA. The inactivation of TF1 by FSBA in the absence of chlorpromazine was complex and was not included in this comparison. Chlorpromazine protected MF1 and EF1 against cold inactivation. Whereas 100 microM chlorpromazine afforded about 90% stabilization of MF1 at 4 degrees C, only about 30% stabilization of EF1 was observed under the same conditions in the presence of 400 microM chlorpromazine. Each of the ATPases was inactivated by the structural analog of chlorpromazine, quinacrine mustard. Whereas 5 mM ATP and 5 mM ADP protected MF1 and TF1 against inactivation by 0.5 mM quinacrine mustard, the rate of inactivation of EF1 by quinacrine mustard was accelerated fourfold by 5 mM ATP and slightly accelerated by 5 mM ADP.
 ...
PMID:The varied responses of different F1-ATPases to chlorpromazine. 285 48

The discovery of a cold-labile cytosolic acetyl-CoA hydrolase of high activity in rat liver by Prass et al. [(1980) J. Biol. Chem. 255, 5215-5223] has questioned the importance of mitochondrial acetyl-CoA hydrolase for the formation of free acetate [Grigat et al. (1979) Biochem. J. 177, 71-79] under physiological conditions. Therefore this problem has been reevaluated by comparing various properties of the two enzymes. Cold-labile cytosolic acetyl-CoA hydrolase bands with an apparent Mr of 68000 during SDS/polyacrylamide gel electrophoresis, while the native enzyme elutes in two peaks with apparent Mr of 136000 and 245000 during gel chromatography in the presence of 2 mM ATP. The mitochondrial enzyme elutes under the same conditions with an apparent Mr of 157000. Under conditions where the cold-labile enzyme binds strongly to DEAE-Bio-Gel and ATP-agarose, the mitochondrial enzyme remains unbound. The cold-labile enzyme can be activated 14-fold by ATP, half-maximal activation occurring already at 40 microM ATP. AdoPP[NH]P, AdoPP[CH2]P and GTP have a similar though weaker effect. ADP as well as GDP can completely inhibit the cold-labile enzyme with 50% inhibition occurring for both nucleotides at about 1.45 microM. The binding of ATP and ADP is competitive. Acetyl phosphate and pyrophosphate have no effect on the activity of the cold-labile enzyme. The mitochondrial acetyl-CoA hydrolase is not affected by these nucleotides. CoASH is a strong product inhibitor (approximately equal to 80% inhibition at 40 microM CoASH) of the cold-labile enzyme, but only a weak inhibitor of the mitochondrial enzyme. Under in vivo conditions the activity of the cold-labile cytosolic acetyl-CoA hydrolase can be no more than 7% of the activity calculated for mitochondrial acetyl-CoA hydrolase under the same conditions. Accordingly the mitochondrial enzyme seems to be mainly responsible for the formation of free acetate by the intact liver, especially in view of the fact that the substrate specificity of the mitochondrial enzyme is much higher (activity ratios acetyl-CoA/butyryl-CoA 4.99 and 1.16 for the mitochondrial and the cold-labile enzyme respectively). Alloxan diabetes neither increased the activity of the cold-labile enzyme nor that of the mitochondrial enzyme. No experimental support has been found yet for the hypothesis that the acetyl-CoA hydrolase activity of the cold-labile enzyme represents the side-activity of an acetyl-transferase.
 ...
PMID:On the regulation of cold-labile cytosolic and of mitochondrial acetyl-CoA hydrolase in rat liver. 285 46

F1-ATPase of rat liver was examined for its capacity to interact with both metal ions and nucleotides and for the effect of covalent ATPase inhibitors on these interactions. As isolated, rat liver F1 contains about 2 mol of Mg2+/mol of F1, 1 mol of which can be removed or exchanged. The remaining mole of Mg2+ per mole of F1 remains very tightly associated with F1 and is recovered in the alpha gamma fraction after cold denaturation. Rat liver F1 also contains as isolated a nearly equivalent amount of nucleotide (approximately 1.7 mol/mol of F1) which is readily removed by incubation at room temperature followed by column centrifugation. The "2 Mg2+ enzyme" binds almost 3 mol of 5'-adenylyl imidodiphosphate (AMP-PNP)/mol of F1 in the presence or absence of added divalent cation. When divalent cation is present as Co2+, an equivalent activator to Mg2+ in the ATPase reaction, 1 mol of F1 binds 3 mol of both AMP-PNP and Co2+. under these conditions, the very tight Mg2+ site remains loaded, the exchangeable Mg2+ site is replaced with AMP-PNPCo, and two additional AMP-PNPCo sites are filled. At this point, ADP can be loaded onto the enzyme as a fourth nucleotide at a site separate and distinct from the AMP-PNP sites. Significantly, rat liver F1 contains only a single readily detectable ADP binding site in the presence or absence of divalent cation.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Ligand binding studies of the F1 moiety of rat liver ATP synthase: implications about the enzyme's structure and mechanism. 288 76

Acyl-CoA hydrolase activities were studied in brown adipose tissue from hamsters. A latent activity was observed in isolated mitochondria. Two peaks of activity were clearly visible in mitochondria, one with an optimum at propionyl-CoA ("short-chain hydrolase") and one with an optimum at nonanoyl-CoA ("medium-chain hydrolase"); there was only low activity toward palmitoyl-CoA and longer-chain acyl-CoAs. In subcellular fractionation experiments, the activity of the short-chain and the medium-chain hydrolase fully followed that of the mitochondrial matrix marker enzyme 2-oxoglutarate dehydrogenase. The specific activity of the hydrolases in the mitochondrial fraction was doubled after cold acclimation. beta-NADH inhibited the short- and medium-chain hydrolases; alpha-NADH, NADPH, and NAD+ were without effect. ADP stimulated the short- and medium-chain hydrolases; ATP and AMP were practically without effect. Evidence is presented to indicate that NADH and ADP interact on the enzyme at the same site and that ADP is essential for the maintenance of the short- and medium-chain enzyme activities. A positive effect of KCl was found on the short- and medium-chain hydrolase activities. Also, the divalent ions Ca2+ and Mg2+ were stimulatory, but only Ca2+ was able to overcome NADH inhibition, possibly due to interaction directly with NADH. It is concluded that brown adipose tissue mitochondria, besides a conventional type of acyl-CoA hydrolase, contain two species of a novel type of acyl-CoA hydrolases which are characterized by being regulated by ADP and NADH (interacting at a common site) and by having an obligatory requirement for ADP.
 ...
PMID:A novel type of short- and medium-chain acyl-CoA hydrolases in brown adipose tissue mitochondria. 290 16

Cold labile extramitochondrial acetyl-CoA hydrolase (dimeric form) purified from rat liver was activated by various nucleoside triphosphates and inhibited by various nucleoside diphosphates. Activation of acetyl-CoA hydrolase by ATP was inhibited by a low concentration of ADP (Ki congruent to 6.8 microM) or a high concentration of AMP (Ki congruent to 2.3 mM). ADP and AMP were competitive inhibitors of ATP. A Scatchard plot of the binding of ATP to acetyl-CoA hydrolase (dimer) at room temperature gave a value of 25 microM for the dissociation constant with at least 2 binding sites/mol of dimer. Cold-treated monomeric enzyme also associated with ATP-agarose, suggesting that the monomeric form of the enzyme also has a nucleotide binding site(s), probably at least 1 binding site/mol of monomer. Phenylglyoxal or 2,3-butanedione, both of which modify arginyl residues of protein, inactivated acetyl-CoA hydrolase. ATP (an activator) greatly protected acetyl-CoA hydrolase from inactivation by these reagents, while ADP (an inhibitor) greatly (a substratelike, competitive inhibitor), and CoASH (a product) were less effective. However, addition of ADP plus valeryl-CoA (or CoASH) effectively prevented the inactivation by 2,3-butanedione, but that is not the case for phenylglyoxal. These results suggest that one or more arginyl residues are involved in the nucleotide binding site of extramitochondrial acetyl-CoA hydrolase and that their nucleotide binding sites locate near the substrate binding site.
 ...
PMID:Binding of nucleotides to an extramitochondrial acetyl-CoA hydrolase from rat liver. 290 53

Coronary blood flow might be reduced by platelet aggregates or by vasospasm induced by platelet-produced thromboxane A2. Therefore the effects of the platelet inhibitor ticlopidine (500 mg daily) on platelet function and on exercise tolerance were investigated in a double-blind placebo-controlled study in 38 middle-aged men with stable incapacitating angina pectoris. Before and after 4 and 8 weeks of treatment, exercise tests were performed in warm and cold environments. The in vitro platelet reactivity to ADP was determined at rest and the plasma levels of beta-thromboglobulin (BTG) and platelet factor 4 (PF4) were measured before and immediately after exercise. There were no signs of increased platelet activity at rest or after exercise as judged by the levels of BTG and PF4. Despite a potent inhibition of platelet reactivity to ADP in vitro during ticlopidine treatment, the exercise tolerance was reduced in exercise tests in both warm and cold environments and in daily life. Therefore platelet activity does not seem to play any significant role in exercise tolerance in the stable phase of angina pectoris.
 ...
PMID:Effects of the platelet inhibitor ticlopidine on exercise tolerance in stable angina pectoris. 294 74

Distinct populations of subsarcolemmal (SS) and inter-fibrillar (IF) rat cardiac mitochondria were studied following 15 and 30 minutes of warm and cold global ischemia. The respiratory control index, state 3, state 4, adenosine diphosphate-oxygen ratio, and specific enzyme activities of these mitochondrial populations were examined. The subsarcolemmar and IF mitochondria were both severely uncoupled and inhibited by warm ischemia. However, IF mitochondria had a higher RCI at each ischemic interval. In cold ischemia, IF mitochondria were not injured compared with control specimens. Subsarcolemmar mitochondria showed a trend towards a lower RCI that was statistically significant at 30 minutes with succinate as a substrate. These data implicate a differential injury of ischemia on the compartmentalized bioenergy metabolism of the myocardial cell.
 ...
PMID:Experimental myocardial ischemia. Differential injury of mitochondrial subpopulations. 298 44

The bacteriophage T4 uvsX gene is a nonessential gene required for normal levels of DNA repair, recombination, and replication. We demonstrate that plasmids containing the T4 DNA approximately 300-2900 base pairs upstream of T4 gene 41 express a biologically active uvsX protein. This uvsX protein imparts increased survival to UV-irradiated T4 uvsX- phage and decreases the T4 uvsX- mutant suppression of a conditionally lethal T4 mutant in the gene 49 recombination nuclease. The uvsX protein purified from cells with a uvsX+ plasmid catalyzes ATP hydrolysis to ADP and AMP and, in the presence of the T4 gene 32 helix-destablizing protein, ATP-dependent strand exchange between homologous circular single-stranded and linear duplex DNA. These results agree with the recent characterization of uvsX protein from T4-infected cells by Yonesaki et al. (Yonesaki, T., Ryo, Y., Minagawa, T., and Takahashi, H. (1985) Eur. J. Biochem. 148, 127-134) and by Formosa and Alberts (Formosa, T., and Alberts, B.M. (1984) Cold Spring Harbor Symp. Quant. Biol. 49, 363-370). In addition, we find that under some reaction conditions strand exchange is catalyzed by uvsX protein in the absence of 32 protein. The level of the uvsX protein expressed by the uvsX+ plasmids is high and independent of the orientation of the T4 DNA within the vector. This suggests that transcription promoter(s) lie upstream of the uvsX gene on the cloned T4 DNA. In vitro transcription of T4 DNA restriction fragments reveals two tandem promoters whose transcripts initiate approximately 500 and 600 nucleotides upstream of the uvsX gene and extend through the gene.
 ...
PMID:Cloning of the bacteriophage T4 uvsX gene and purification and characterization of the T4 uvsX recombination protein. 300 20

Functional and biochemical alterations of platelets in patients suffering from atherosclerosis were studied in our laboratory. One of the most striking alterations observed is in the platelet active glucose transport system. The Na+/K+ gradient dependent active transport system of glucose is found to be absent in the platelets of atherosclerotics. The platelet glucose transport kinetics in these subjects give unsaturable and linear kinetics. Furthermore, the specific glucose binding protein activity detected in the incubation fluid after cold osmotic shock to the platelets of normal subjects is found to be absent in the platelets of atherosclerotics. The platelet active glucose transport system is normal in juvenile onset diabetics, whereas it is impaired in maturity onset diabetics with clinical manifest atherosclerosis. The release inducers like ADP, adrenalin and collagen exert no effect on the platelet active glucose transport system. The specific glucose-binding protein is an unreleasable protein in the platelets of normal subjects. Hence, the absence of active glucose transport system in atherosclerotics is not due to the activated platelets in circulation.
 ...
PMID:Alteration of platelet glucose transport system in atherosclerosis. 301 May 81


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>