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Induced Aggregation (induced + aggregation)

Distribution by Scientific Domains

Medical Sciences	60%

Selected Abstracts

Structure,activity relationships of isoeugenol-based chlorophenylpiperazine derivatives on serotonergic/adrenergic receptor, platelet aggregation, and lipid peroxidation

DRUG DEVELOPMENT RESEARCH, Issue 5 2010
Kuo-Ping Shen
Abstract Three isoeugenol-based eugenosedin chlorphenylpiperazine derivatives, Eu-A, Eu-B, and Eu-C, were synthesized and tested for their serotonergic, adrenergic antagonist, antioxidant, and anti-aggregation activities. In radioligand binding assays, all three agents displayed significant binding affinities on ,1, ,2, ,1, 5-HT1B, and 5-HT2A receptors. In human platelet, they inhibited epinephrine and 5-HT-induced aggregation, and in human platelet with ,2 and 5-HT2A receptors they had a competitive binding effect. Eu-B and Eu-C were more potent than Eu-A. All compounds had antioxidant effects derived from aryloxypropanolamine. Eu- A, Eu-B, or Eu-C (1, 3, 5,mg/kg iv) given to normotensive Wistar rats produced a dose-dependent decrease in mean arterial blood pressure and heart rate and when injected into the cisternum, Eu-A, Eu-B, or Eu-C (0.3, 0.03,µmol) increased blood pressure within 15,min. Pretreatment with any of the three agents inhibited clonidine (38,pmol)-induced hypotension. In vitro experiments, Eu-A, Eu-B, or Eu-C (1, 10, and 100,µM) competitively antagonized norepinephrine-, clonidine-, and 5-HT (10,8,10,4,M)-induced vasocontraction in isolated rat aorta, and competitively antagonized isoproterenol (10,8,10,4,M)-induced positive inotropic effects in a concentration-dependent manner in the isolated rat left atrium. In isolated rabbit ear arteries sensitized with 16,mM K+, all three agents antagonized 5-nonyloxytryptamine- and 5-HT-induced vasocontractions. These findings show that Eu-A, Eu-B, and Eu-C possess functional ,1, ,2, ,1, 5-HT1B, and 5-HT2A receptor blocking activities. In conclusion, the changes in the position of chloride at phenylpiperazine influenced the serotonergic receptor, adrenoceptor antagonistic activities, but not anti-aggregation and antioxidant activities. Drug Dev Res 71:1,9, 2010. © 2010 Wiley-Liss, Inc. [source]

Differential response of platelets to chemokines: RANTES non-competitively inhibits stimulatory effect of SDF-1,

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 1 2004
B. Shenkman
Summary.,Background:,Among the chemokines related to CXC and CC receptor groups and released from platelets, leukocytes and endothelial cells, SDF-1, TARC and MDC have been found to be platelet agonists. Platelets do not contain SDF-1,. In contrast, RANTES is constitutively present in platelet ,-granules and released upon platelet activation. Objectives:,To study a possible role of RANTES as a modulator of SDF-1, effect on platelets, in relation to CXCR4 and various CC receptors. Methods:,CXCR-4 (CXCL12) receptor expression and platelet activation were evaluated by flow cytometry, platelet deposition was studied by cone and plate(let) analyzer, and platelet aggregation by turbidometric aggregometry. Results:,Flow cytometry studies revealed similar expression of CXCR-4, the specific receptor of SDF-1, on intact, inactivated, and activated platelets. Preincubation of platelets with RANTES affected neither CXCR-4 expression, nor SDF-1, binding to the platelet membrane. In the presence of fibrinogen, SDF-1, activated gel-filtered platelets. RANTES did not activate platelets, but substantially (by 70%) inhibited SDF-1,-induced fibrinogen binding. Similarly, RANTES abrogated the promoting effect of SDF-1, on whole blood platelet adhesion to endothelial cell monolayer under venous flow conditions. In platelet-rich plasma, RANTES moderately inhibited SDF-1,-induced platelet aggregation, while it did not affect aggregation induced by thrombin-receptor activation peptide, adenosine diphosphate, or phorbol 12-myristate 13-acetate. A synergistic inhibitory effect of RANTES and prostaglandin E1 used at subthreshold concentrations, on SDF-1,-induced aggregation and SDF-1,-induced fibrinogen binding to platelets was observed, which may suggest involvement of RANTES in a cAMP-dependent signal transduction pathway. Conclusions:,RANTES non-competitively inhibits activation of platelets by SDF-1,, and thus may play a regulatory role in platelet response to inflammation. [source]

Fluorescence-based soft-sensor for monitoring ,-lactoglobulin and ,-lactalbumin solubility during thermal aggregation

BIOTECHNOLOGY & BIOENGINEERING, Issue 3 2008
Rand Elshereef
Abstract A soft-sensor for monitoring solubility of native-like ,-lactalbumin (,-LA) and ,-lactoglobulin (,-LG) and their aggregation behavior following heat treatment of mixtures under different treatment conditions was developed using fluorescence spectroscopy data regressed with a multivariate Partial Least Squares (PLS) regression algorithm. PLS regression was used to correlate the concentrations of ,-LA and ,-LG to the fluorescence spectra obtained for their mixtures. Data for the calibration and validation of the soft sensor was derived from fluorescence spectra. The process of thermal induced aggregation of ,-LG and ,-LA protein in mixtures, which involves the disappearance of native-like proteins, was studied under various treatment conditions including different temperatures, pH, total initial protein concentration and proportions of ,-LA and ,-LG. It was demonstrated that the multivariate regression models used could effectively deconvolute multi-wavelength fluorescence spectra collected under a variety of process conditions and provide a fairly accurate quantification of respective native-like proteins despite the significant overlapping between their emission profiles. It was also demonstrated that a PLS model can be used as a black-box prediction tool for estimating protein aggregation when combined with simple mass balances. Bioeng. 2008;99: 567,577. © 2007 Wiley Periodicals, Inc. [source]

Prevention of thermal induced aggregation of cytochrome c at isoelectric pH values by polyanions

BIOTECHNOLOGY & BIOENGINEERING, Issue 3 2006
Diana Fedunová
Abstract Differential scanning calorimetry, viscometry, optical and CD spectroscopy were used to characterize the influence of two polyanions, poly(vinylsulfate) (PVS), and poly(4-styrene-sulfonate) (PSS) on thermal transition reversibility of ferricytochrome c at or near isoelectric pH. In these conditions, both PVS and PSS enhance the thermal transition reversibility of cytochrome c by preventing the aggregation of denatured protein molecules. Data indicate that the polyanions are in complex with cytochrome c that is stabilized by synergistic effect of Coulombic and non-Coulombic interactions. © 2005 Wiley Periodicals, Inc. [source]

2135: Influence of Hsp90 and HDAC inhibition and tubulin acetylation on perinuclear protein aggregation in human retinal pigment epithelial cells

ACTA OPHTHALMOLOGICA, Issue 2010
K KAARNIRANTA
Purpose Retinal pigment epithelial (RPE) cells are continually exposed to oxidative stress that contributes to protein misfolding, aggregation and functional abnormalities during aging. The protein aggregates formed at the cell periphery are delivered along the microtubulus network by dynein dependent retrograde trafficking to a juxtanuclear location. Methods Cellular organelles were analysed by transmission electron microscopy of ARPE-19 cells exposed 5 µM MG-132, 0.25 µM geldanamycin (GA), 1 µM trichostatin A (TSA), 1 µM taxol (TAX) or 5 µM nocodazole (NOC) for 24 hours. In addition, the cells were treated simultaneously with GA or TSA or TAX or NOC and MG-132 up to 24 hours. Ubiquitin, Hsp90, Hsp70, acetylated tubulin and Hsc70 protein levels were analyzed by western blotting. Results Hsp90 inhibition by geldanamycin can effectively suppress proteasome inhibitor, MG-132 ,induced protein aggregation in a way that is an independent of HDAC inhibition, or the tubulin acetylation levels in ARPE-19 cells. However, the tubulin acetylation and polymerization state affects the localization of the proteasome-inhibitor ,induced aggregation. Conclusion Hsp90 inhibition is effectively related to regulation of protein aggregation that is independent of HDAC inhibition or tubulin acetylation levels in the RPE cells. Our findings open new perspectives for understanding the pathogenesis of protein aggregation in retinal cells and can be useful for the development of therapeutic treatments to prevent retinal cell deterioration. [source]