Search results for "binding"
showing 10 items of 3896 documents
Azapropazone binding to human serum albumin
1980
Azapropazone, a new non-steroidal antiinflammatory drug, is strongly bound to human serum albumin. As revealed by Scatchard analysis, one high-affinity binding site with an association constant of about 1.2 x 10(6)M-1 and two low-affinity binding sites with association constants of about 0.05 x 10(6)M-1 were found. While the high-affinity binding site of azapropazone is clearly not identical with the diazepam or digitoxin binding sites of human serum albumin, contradictory evidence was found by optical measurements and displacement studies for the similarity of the azapropazone and the warfarin binding site of human serum albumin. At present, it is suggested that both drugs bind to differen…
DNA replication arrest in response to genotoxic stress provokes early activation of stress-activated protein kinases (SAPK/JNK).
2009
Abstract The impact of DNA damage-induced replication blockage for early activation of stress kinases [stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK)] is largely unknown. Here, we show that induction of dual phosphorylation of SAPK/JNK by the DNA polymerase inhibitor aphidicolin was not ameliorated by additional exposure to ultraviolet (UV) light, indicating that overlapping mechanisms participate in signaling to SAPK/JNK triggered by both agents. UV-induced DNA replication blockage, cyclobutane pyrimidine dimer formation and DNA strand break induction coincided with SAPK/JNK phosphorylation at early (≤ 30 min) but not late (≥ 2 h) time points after exposure. Genotoxin…
Amyloid-β toxicity and tau hyperphosphorylation are linked via RCAN1 in Alzheimer's disease.
2011
Amyloid-β peptide (Aβ) toxicity and tau hyperphosphorylation are hallmarks of Alzheimer’s disease (AD). How their molecular relationships may affect the etiology, progression, and severity of the disease, however, has not been elucidated. We now report that incubation of foetal rat cortical neurons with Aβ up-regulates expression of the Regulator of Calcineurin gene RCAN1, and this is mediated by Aβ-induced oxidative stress. Calcineurin (PPP3CA) is a serine-threonine phosphatase that dephosphorylates tau. RCAN1 proteins inhibit this phosphatase activity of calcineurin. Increased expression of RCAN1 also causes up-regulation of glycogen synthase kinase-3beta (GSK3β), a tau kinase. Thus, incr…
Uptake mechanism of ApoE-modified nanoparticles on brain capillary endothelial cells as a blood-brain barrier model.
2012
Background The blood-brain barrier (BBB) represents an insurmountable obstacle for most drugs thus obstructing an effective treatment of many brain diseases. One solution for overcoming this barrier is a transport by binding of these drugs to surface-modified nanoparticles. Especially apolipoprotein E (ApoE) appears to play a major role in the nanoparticle-mediated drug transport across the BBB. However, at present the underlying mechanism is incompletely understood. Methodology/Principal Findings In this study, the uptake of the ApoE-modified nanoparticles into the brain capillary endothelial cells was investigated to differentiate between active and passive uptake mechanism by flow cytome…
Haptoglobin interacts with apolipoprotein E and beta-amyloid and influences their crosstalk.
2014
Beta-amyloid accumulation in brain is a driving force for Alzheimer's disease pathogenesis. Apolipoprotein E (ApoE) represents a critical player in beta-amyloid homeostasis, but its role in disease progression is controversial. We previously reported that the acute-phase protein haptoglobin binds ApoE and impairs its function in cholesterol homeostasis. The major aims of this study were to characterize the binding of haptoglobin to beta-amyloid, and to evaluate whether haptoglobin affects ApoE binding to beta-amyloid. Haptoglobin is here reported to form a complex with beta-amyloid as shown by immunoblotting experiments with purified proteins, or by its immunoprecipitation in brain tissues …
Temperature‐Responsive Nanoparticles Enable Specific Binding of Apolipoproteins from Human Plasma
2021
Apolipoproteins are an important class of proteins because they provide a so-called stealth effect to nanoparticles. The stealth effect on nanocarriers leads to a reduced unspecific uptake into immune cells and thereby to a prolonged blood circulation time. Herein, a novel strategy to bind apolipoproteins specifically on nanoparticles by adjusting the temperature during their incubation in human plasma is presented. This specific binding, in turn, allows a control of the stealth behavior of the nanoparticles. Nanoparticles with a well-defined poly(N-isopropylacrylamide) shell are prepared, displaying a reversible change of hydrophobicity at a temperature around 32 °C. It is shown by label-f…
Reduced VLDL clearance in ApoeNpc1 mice is associated with increased Pcsk9 and Idol expression and decreased hepatic LDL-receptor levels
2010
Niemann-Pick type C1 (NPC1) promotes the transport of LDL receptor (LDL-R)-derived cholesterol from late endosomes/lysosomes to other cellular compartments. NPC1-deficient cells showed impaired regulation of liver_X receptor (LXR) and sterol regulatory element-binding protein (SREBP) target genes. We observed that Apoe(-/-)Npc1(-/-) mice displayed a marked increase in total plasma cholesterol mainly due to increased VLDL, reflecting decreased clearance. Although nuclear SREBP-2 and Ldlr mRNA levels were increased in Apoe(-/-)Npc1(-/-) liver, LDL-R protein levels were decreased in association with marked induction of proprotein convertase subtilisin/kexin type 9 (Pcsk9) and inducible degrade…
Vascular Activity of (-)-Anonaine, (-)-Roemerine and (-)-Pukateine, Three Natural 6a(R)-1,2-Methylenedioxyaporphines with Different Affinities for α1…
2004
We have studied the mechanism of action of three 6a( R)-1,2-methylenedioxyaporphines as vasorelaxant compounds. The alkaloids assayed showed different affinities for the three human cloned alpha (1)-adrenoceptor (AR) subtypes stably expressed in rat-1 fibroblasts, showing lower affinity for alpha(1B)-AR with regard to the alpha(1A)- or alpha(1D)-subtypes. These three natural compounds are more potent inhibitors of [ (3)H]-prazosin binding than of [ (3)H]-diltiazem binding to rat cerebral cortical membranes. As all these alkaloids inhibited noradrenaline (NA)-induced [ (3)H]-inositol phosphate formation in cerebral cortex and rat tail artery, they may be safely viewed as alpha (1)-AR antagon…
A possible structural determinant of selectivity of boldine and derivatives for the alpha 1A-adrenoceptor subtype.
1996
1. The selectivity of action of boldine and the related aporphine alkaloids, predicentrine (9-O-methylboldine) and glaucine (2,9-O-dimethylboldine) and alpha 1-adrenoceptor subtypes was studied by examining [3H]-prazosin competition binding in rat cerebral cortex. WB 4101 and benoxathian were used as selective alpha 1A-adrenoceptor antagonists. 2. In the competition experiments [3H]-prazosin (0.2 nM) binding was inhibited by WB 4101 and benoxathian. The inhibition curves displayed shallow slopes which could be subdivided into high and low affinity components (pKi = 9.92 and 8.29 for WB 4101, 9.35 and 7.94 for benoxathian). The two antagonists recognized approximately 37% of the sites with h…
Binding of 11-cis retinaldehyde to the partially purified cellular retinaldehyde binding protein from bovine retinal pigment epithelium.
1987
11-cis retinaldehyde binding analysis was performed on a bovine retinal pigment epithelium preparation of cellular retinaldehyde binding protein (CRALBP), whose purity degree was estimated as 75%. Equilibrium binding studies were carried out measuring the replacement of tritium-labeled with unlabeled 11-cis retinaldehyde at 25 degrees C. Analysis of the experimental data both by a direct curve-fitting procedure utilizing a non linear least square regression analysis and by a conventional Scatchard plot revealed a single non-interacting binding site with an apparent equilibrium constant of 0.9 X 10(-7) M. A binding stoichiometry of approximately 1 mol of 11-cis retinaldehyde/mol of binding p…