scholarly journals Inhibitors of caeruloplasmin

1967 ◽  
Vol 105 (1) ◽  
pp. 243-250 ◽  
Author(s):  
G. Curzon ◽  
Barbara E. Speyer
Keyword(s):  
Oxidase Activity ◽  
Structural Unit ◽  
Inverse Relationship ◽  
Molecular Size ◽  
Inhibitory Effect ◽  
Copper Binding ◽  
Binding Properties ◽  
Enzyme Action ◽  
Inhibitory Power ◽  
And Function

1. A method is described by which substances inhibiting caeruloplasmin oxidase activity directly may be distinguished from those acting on stimulatory contaminant iron or on the product of enzyme action. 2. Many previously reported inhibitors, including saturated aliphatic carboxylates, hydrazines, 1,10-phenanthroline, borate and various psycho-active drugs, are found either not to act on the enzyme or to inhibit it only weakly. 3. A series of inorganic anions are compared as inhibitors. Anions such as azide and cyanide with strong copper-binding properties are the most effective inhibitors. There is a general inverse relationship between anion size and inhibitory power. Iodide is anomalous, the order of effectiveness of halides being F−>I−[unk]Cl−>Br−. 4. Multidentate copperchelating ligands have little inhibitory effect. 5. A group of substances containing the structural unit [unk]C=[unk]·CO2H, including fumarate and benzoate, cause inhibition. 6. Relative inhibitions by a series of mono-substituted benzoates are inversely related to molecular size. 7. Results are discussed in relation to earlier work on the disposition and function of the copper atoms of caeruloplasmin.

Sex steroids and their relationship to binding proteins in the serum of the marmoset monkey (Callithrix jacchus)

1983 ◽  
Vol 96 (3) ◽  
pp. 443-450 ◽  
Author(s):  
J. K. Hodges ◽  
S. A. K. Eastman ◽  
N. Jenkins
Keyword(s):  
Sex Steroids ◽  
Luteal Phase ◽  
Inverse Relationship ◽  
Equilibrium Dialysis ◽  
Sex Hormone Binding Globulin ◽  
Binding Properties ◽  
Serum Progesterone ◽  
Pregnant Females ◽  
Marmoset Monkey ◽  
Steroid Binding

A sex hormone binding globulin (SHBG) similar to human SHBG was identified in marmoset serum based on its gel electrophoretic mobility, isoelectric point and steroid binding properties. Levels of serum SHBG were measured in immature and mature males, immature females and females during the luteal phase and pregnancy; serum progesterone, 5α-dihydrotestosterone (5α-DHT), testosterone, oestradiol-17β and oestrone were also measured. Mean (± s.e.m.) concentrations of SHBG in immature males (336 ±19 nmol/l) were higher (P <0·01) than those in mature males (251 ±13 nmol/l), whereas values in the groups of females were similar (359 ± 12, 395 ± 17, 397 ± 39 nmol/l in immature, non-pregnant and pregnant females respectively). There was an inverse relationship between SHBG and the levels of testosterone (r= −0·67) and 5α-DHT (r = −0·86) in males, but the correlation was significant (P <0·05) only for 5α-DHT. There was no correlation between levels of SHBG and oestrogens in males or between levels of SHBG and any of the steroids measured in females. Equilibrium dialysis was used to assess the percentage of steroid in serum in the unbound form. Mean percentage values for unbound testosterone and 5α-DHT were lower in immature males than in mature males (P <0·01) and negatively correlated with levels of SHBG (r = −0·78, testosterone; r = −0·56, 5α-DHT).

scholarly journals Crystal structure and RNA-binding properties of an Hfq homolog from the deep-branching Aquificae: conservation of the lateral RNA-binding mode

2017 ◽  
Vol 73 (4) ◽  
pp. 294-315 ◽  
Author(s):  
Kimberly A. Stanek ◽  
Jennifer Patterson-West ◽  
Peter S. Randolph ◽  
Cameron Mura
Keyword(s):  
Rna Binding ◽  
Binding Pocket ◽  
Binding Mode ◽  
Evolutionary Conservation ◽  
Aquifex Aeolicus ◽  
Binding Properties ◽  
Bacterial Phyla ◽  
Mrna Targets ◽  
Small Regulatory Rnas ◽  
And Function

The host factor Hfq, as the bacterial branch of the Sm family, is an RNA-binding protein involved in the post-transcriptional regulation of mRNA expression and turnover. Hfq facilitates pairing between small regulatory RNAs (sRNAs) and their corresponding mRNA targets by binding both RNAs and bringing them into close proximity. Hfq homologs self-assemble into homo-hexameric rings with at least two distinct surfaces that bind RNA. Recently, another binding site, dubbed the `lateral rim', has been implicated in sRNA·mRNA annealing; the RNA-binding properties of this site appear to be rather subtle, and its degree of evolutionary conservation is unknown. An Hfq homolog has been identified in the phylogenetically deep-branching thermophileAquifex aeolicus(Aae), but little is known about the structure and function of Hfq from basal bacterial lineages such as the Aquificae. Therefore,AaeHfq was cloned, overexpressed, purified, crystallized and biochemically characterized. Structures ofAaeHfq were determined in space groupsP1 andP6, both to 1.5 Å resolution, and nanomolar-scale binding affinities for uridine- and adenosine-rich RNAs were discovered. Co-crystallization with U6RNA reveals that the outer rim of theAaeHfq hexamer features a well defined binding pocket that is selective for uracil. ThisAaeHfq structure, combined with biochemical and biophysical characterization of the homolog, reveals deep evolutionary conservation of the lateral RNA-binding mode, and lays a foundation for further studies of Hfq-associated RNA biology in ancient bacterial phyla.

scholarly journals Metabolic aspects of the secretion of stored compounds from blood platelets. The effect of NaF at different pH on nucleotide metabolism and function of washed platelets

1981 ◽  
Vol 194 (1) ◽  
pp. 187-192 ◽  
Author(s):  
E H Mürer ◽  
K Davenport ◽  
E Siojo ◽  
H J Day
Keyword(s):  
Time Course ◽  
Adenine Nucleotides ◽  
Blood Platelets ◽  
Fluoride Concentration ◽  
Indirect Evidence ◽  
Inhibitory Effect ◽  
Nucleotide Metabolism ◽  
Wide Range ◽  
And Function ◽  
Special Circumstances

The purpose of this study was to investigate the response of human blood platelets to fluoride at different pH. The results were as follows. (1) Fluoride induced secretion faster and at a lower concentration when pH was lowered. (2) Platelets exposed to 2 mM-fluoride at 0 degrees C at pH 5.3 underwent secretion when first pH and then temperature was raised, although no secretion was seen at 2 mM-fluoride concentration in the absence of the preincubation at low pH. (3) The concentration of [14C]ATP in platelets decreased steeply in response to fluoride before induction of secretion. Addition of antimycin blocked or partly inhibited secretion. Fluoride thus exerts an inhibitory effect on platelet glycolysis before induction of secretion. (4) Fluoride accumulated in the platelet pellet by a time course that preceded secretion. The accumulation was faster and greater at pH 6 than at 7.4. These four points are taken as indirect evidence that fluoride has to penetrate to the interior of the platelet to induce secretion. The activation takes place over a wide range of acid pH in contrast with induction of platelet function via the outside of the plasma membrane. In addition evidence is presented that the salvage pathway may under special circumstances play an important role in the re-synthesis of platelet adenine nucleotides.

scholarly journals Piceatannol attenuates RANKL-induced osteoclast differentiation and bone resorption by suppressing MAPK, NF-κB and AKT signalling pathways and promotes Caspase3-mediated apoptosis of mature osteoclasts

2019 ◽  
Vol 6 (6) ◽  
pp. 190360 ◽  
Author(s):  
Liuliu Yan ◽  
Lulu Lu ◽  
Fangbin Hu ◽  
Dattatrya Shetti ◽  
Kun Wei
Keyword(s):  
Bone Resorption ◽  
Osteoclast Differentiation ◽  
Giant Cells ◽  
Inhibitory Effect ◽  
Osteoclast Formation ◽  
Bone Diseases ◽  
Signalling Pathways ◽  
Dependent Manner ◽  
Underlying Mechanisms ◽  
And Function

Osteoclasts are multinuclear giant cells that have unique ability to degrade bone. The search for new medicines that modulate the formation and function of osteoclasts is a potential approach for treating osteoclast-related bone diseases. Piceatannol (PIC) is a natural organic polyphenolic stilbene compound found in diverse plants with a strong antioxidant and anti-inflammatory effect. However, the effect of PIC on bone health has not been scrutinized systematically. In this study, we used RAW264.7, an osteoclast lineage of cells of murine macrophages, to investigate the effects and the underlying mechanisms of PIC on osteoclasts. Here, we demonstrated that PIC treatment ranging from 0 to 40 µM strongly inhibited osteoclast formation and bone resorption in a dose-dependent manner. Furthermore, the inhibitory effect of PIC was accompanied by the decrease of osteoclast-specific genes. At the molecular level, PIC suppressed the phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK1/2), NF-κB p65, IκBα and AKT. Besides, PIC promoted the apoptosis of mature osteoclasts by inducing caspase-3 expression. In conclusion, our results suggested that PIC inhibited RANKL-induced osteoclastogenesis and bone resorption by suppressing MAPK, NF-κB and AKT signalling pathways and promoted caspase3-mediated apoptosis of mature osteoclasts, which might contribute to the treatment of bone diseases characterized by excessive bone resorption.

Stored calcium modulates inositol phosphate synthesis in cultured smooth muscle cells

1992 ◽  
Vol 263 (2) ◽  
pp. C535-C539 ◽  
Author(s):  
D. M. Berman ◽  
W. F. Goldman
Keyword(s):  
Smooth Muscle ◽  
Sarcoplasmic Reticulum ◽  
Smooth Muscle Cells ◽  
Inverse Relationship ◽  
Inositol Phosphates ◽  
Inositol Phosphate ◽  
Muscle Cells ◽  
Inhibitory Effect ◽  
A7r5 Cells ◽  
Cultured Smooth Muscle Cells

Cytosolic Ca2+ concentrations ([Ca2+]cyt) and [3H]inositol phosphates ([3H]InsP) were correlated while varying the Ca2+ content of the sarcoplasmic reticulum (SR) in cultured A7r5 cells at rest and during activation with [Arg8]-vasopressin (AVP). Thapsigargin (TG) raised and superfusion with 0 Ca2+ lowered [Ca2+]cyt, but both treatments decreased SR Ca2+ and AVP-evoked Ca2+ transients. Neither TG nor 0 Ca2+ affected basal [3H]InsP, but both treatments increased AVP-evoked synthesis of [3H]InsP. Exposure for several minutes to 40 mM K+ solution, BAY K 8644, or low-Na+ solution all elevated [Ca2+]cyt and, thereby, increased SR Ca2+, as manifested by augmented AVP-evoked Ca2+ transients. In all three cases, AVP-evoked, but not basal, [3H]InsP were reduced. The inhibitory effect of 40 mM K+ on AVP-evoked [3H]InsP synthesis was blocked when SR Ca2+ uptake was prevented by TG. Brief (30-s) exposures to 40 mM K+, which elevated [Ca2+]cyt but not SR Ca2+ loading, did not modify AVP-evoked [3H]InsP synthesis or Ca2+ transients. These results demonstrate an inverse relationship between SR Ca2+ content and evoked [3H]-InsP synthesis. Moreover, they suggest that SR Ca2+ may serve as a signal that modulates sarcolemmal [3H]InsP formation.

Copper-Binding Properties and Structures of Methanobactins from Methylosinus trichosporium OB3b

2011 ◽  
Vol 50 (4) ◽  
pp. 1378-1391 ◽  
Author(s):  
Abdelnasser El Ghazouani ◽  
Arnaud Baslé ◽  
Susan J. Firbank ◽  
Charles W. Knapp ◽  
Joe Gray ◽  
...  
Keyword(s):  
Copper Binding ◽  
Methylosinus Trichosporium Ob3b ◽  
Binding Properties ◽  
Methylosinus Trichosporium
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