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51.
Aikaterini A. Zompra Vassiliki Magafa Dimitra G. Chryssanthi Fotini N. Lamari Georgios A. Spyroulias Theodosia Maina Berthold A. Nock Nikos K. Karamanos Paul Cordopatis 《International journal of peptide research and therapeutics》2007,13(1-2):143-149
GnRH analogues have been extensively used in oncology to induce reversible chemical castration due to their hypophysiotropic
action. In addition to that, it has recently been shown that many malignant cells, such as breast cancer cells, locally produce
GnRH and express the GnRH receptor/s. In order to investigate the structure-activity relationships in both pituitary and extrapituitary
biological systems, we synthesized eight new GnRH analogues with modifications in the N-terminal part and/or in position 6
and studied their pituitary binding affinity (in αT3-1 cell membranes) and effect on breast cancer (MCF-7) cell proliferation.
2-Amino-4-pyrrolidinothieno[2,3-d]pyrimidine-6-carboxylic acid (ATPC) was incorporated instead of pGlu1-His2- and/or Gly6 was substituted by α-aminoisobutyric acid, D-Leu and D-Lys (alone or covalently linked to Gly, Ala, Sar, ATPC). Most GnRH
analogues lacked the carboxy-terminal Gly10-amide of GnRH and an ethylamide residue was added to Pro9, a modification common in many potent GnRH agonists, such as leuprolide ([D-Leu6, des-Gly10]-GnRH-NHEt. Results show differential impact of these modifications on the binding affinity to the GnRH receptor in mouse
pituitary cells and on the inhibition of human breast cancer cell proliferation. ATPC in the N-terminus resulted in analogues
with low binding affinity but high antiproliferative effect. Substitutions in position 6 always resulted in high binding affinities.
In particular, [D-Lys6(Gly), desGly10]-GnRH-NHEt and [D-Lys6(Sar), desGly10]-GnRH-NHEt have higher pituitary binding affinity than leuprolide, but only the latter had significant antiproliferative
effect on both MCF-7 and MDA-MB-231 cells. These results contribute to the on-going research for more potent GnRH analogues.
Abbreviations of common amino acids are in accordance with the recommendations of IUPAC-IUB Joint Commission on Biochemical
Nomenclature: Arch. Biochem. Biophys. 206, pp.v-xxii (1988), J. Biol. Chem. 264, 668–673 (1989) or J. Peptide Sci. 9, 1–8
(2003). 相似文献
52.
Konstantinos C Tsolis Ekaterini S Bei Ioanna Papathanasiou Fotini Kostopoulou Vassiliki Gkretsi Kalliopi Kalantzaki Konstantinos Malizos Michalis Zervakis Aspasia Tsezou Anastassios Economou 《Clinical proteomics》2015,12(1):12
Background
Osteoarthritis (OA) is a multi-factorial disease leading progressively to loss of articular cartilage and subsequently to loss of joint function. While hypertrophy of chondrocytes is a physiological process implicated in the longitudinal growth of long bones, hypertrophy-like alterations in chondrocytes play a major role in OA. We performed a quantitative proteomic analysis in osteoarthritic and normal chondrocytes followed by functional analyses to investigate proteome changes and molecular pathways involved in OA pathogenesis.Methods
Chondrocytes were isolated from articular cartilage of ten patients with primary OA undergoing knee replacement surgery and six normal donors undergoing fracture repair surgery without history of joint disease and no OA clinical manifestations. We analyzed the proteome of chondrocytes using high resolution mass spectrometry and quantified it by label-free quantification and western blot analysis. We also used WebGestalt, a web-based enrichment tool for the functional annotation and pathway analysis of the differentially synthesized proteins, using the Wikipathways database. ClueGO, a Cytoscape plug-in, is also used to compare groups of proteins and to visualize the functionally organized Gene Ontology (GO) terms and pathways in the form of dynamical network structures.Results
The proteomic analysis led to the identification of a total of ~2400 proteins. 269 of them showed differential synthesis levels between the two groups. Using functional annotation, we found that proteins belonging to pathways associated with regulation of the actin cytoskeleton, EGF/EGFR, TGF-β, MAPK signaling, integrin-mediated cell adhesion, and lipid metabolism were significantly enriched in the OA samples (p ≤10−5). We also observed that the proteins GSTP1, PLS3, MYOF, HSD17B12, PRDX2, APCS, PLA2G2A SERPINH1/HSP47 and MVP, show distinct synthesis levels, characteristic for OA or control chondrocytes.Conclusion
In this study we compared the quantitative changes in proteins synthesized in osteoarthritic compared to normal chondrocytes. We identified several pathways and proteins to be associated with OA chondrocytes. This study provides evidence for further testing on the molecular mechanism of the disease and also propose proteins as candidate markers of OA chondrocyte phenotype.Electronic supplementary material
The online version of this article (doi:10.1186/s12014-015-9085-6) contains supplementary material, which is available to authorized users. 相似文献53.
54.
Kalea AZ Lamari FN Theocharis AD Cordopatis P Schuschke DA Karamanos NK Klimis-Zacas DJ 《The Journal of nutritional biochemistry》2006,17(2):109-116
It has been documented that increased intake of polyphenols may provide protection against coronary heart disease and stroke. Blueberries (Vaccinium angustifolium) are one of the richest sources of antioxidants among fruits and vegetables. Phenolic compounds from berry extracts inhibit human low density lipoprotein and liposome oxidation. Glycosaminoglycans (GAGs) and proteoglycans (PGs) are structural components of aortas with great structural diversity. Their interaction with compounds such as enzymes, cytokines, growth factors, proteins and lipoproteins and their subsequent role in degenerative diseases has been documented. We investigated the effects of a diet rich in blueberries on the content and structure of GAGs. Sprague-Dawley rats were fed either a control (C) or a blueberry (B) diet for 13 weeks. Aortic tissue GAGs were isolated with papain digestion, alkaline borohydride treatment and anion-exchange chromatography. Cellulose acetate electrophoresis and treatment of the fractions with specific lyases revealed the presence of three GAG populations, i.e. hyaluronan (HA), heparan sulfate (HS) and galactosaminoglycans (GalAGs). Disaccharide composition was determined by high-performance capillary electrophoresis following enzymatic degradation. A 13% higher amount of total GAGs in aortas of B-fed rats was attributed to a higher content of GalAGs (67%). Determination of the sulfated disaccharides showed an overall lower concentration of oversulfated disaccharides in both HS and GalAG populations in the aortas of the B group. Our results demonstrate for the first time that a diet rich in blueberries results in structural alterations in rat aortic tissue GAGs. These changes may affect cellular signal transduction pathways and could have major consequences for the biological function of GAG molecules within the vascular environment. 相似文献
55.
Anastasia Z. Kalea Fotini N. Lamari Achilleas D. Theocharis Dale A. Schuschke Nikos K. Karamanos Dorothy J. Klimis-Zacas 《Biometals》2006,19(5):535-546
We examined the effect of dietary Mn on the composition and structure of heparan sulfate (HS) glycosaminoglycans (GAGs) of
rat aorta. Animals were randomly assigned to either a Mn deficient (MnD), adequate (MnA) or supplemented (MnS) diet (Mn<1,
10–15 and 45–50 ppm, respectively). After 15 weeks, aortic tissue GAGs were isolated with papain digestion, alkaline borohydride
treatment and anion-exchange chromatography. Cellulose acetate electrophoresis and treatment of the fractions with specific
lyases revealed the presence of three GAG populations, i.e. hyaluronan (HA), heparan sulfate (HS) and galactosaminoglycans
(GalAGs). Disaccharide composition of the HS fractions was determined by HPCE following treatment with heparin lyases I, II
and III. In MnS aortas we observed increased concentration of total GalAGs and decreased concentration of HS and HA, when
compared to MnA aortas. Aortas from MnD and MnA rats appeared to have similar distribution of individual GAGs. Heparan sulfate
chains of MnS aortas contained higher (41%) concentration of non-sulfated units compared to MnA ones. Variable amounts of
trisulfated and disulfated units were found only in MnD and MnA groups but not in MnS. Our results demonstrate that HS biosynthesis
in the rat aorta undergoes marked structural modifications that depend upon dietary Mn intake. The reduced expression and
undersulfation of HSPGs with Mn supplementation might indicate a reduced ability of vascular cells to interact with biologically
active molecules such as growth factors. Alterations in cell-membrane binding ability to a variety of extracellular ligands
might affect signal-transduction pathways and arterial functional properties. 相似文献
56.
Ghost mtDNA haplotypes generated by fortuitous NUMTs can deeply disturb infra‐specific genetic diversity and phylogeographic pattern 下载免费PDF全文
Julien Haran Fotini Koutroumpa Emmanuelle Magnoux Alain Roques Géraldine Roux 《Journal of Zoological Systematics and Evolutionary Research》2015,53(2):109-115
Nuclear copies of mitochondrial DNA (NUMTs or mitochondrial pseudogenes) are known to impede the detection of interspecific genetic diversity. But the effect of these artifacts on phylogeographic reconstruction remains under evaluated. In this study, we analysed a set of 115 sequences of a fragment of the cytochrome c oxidase subunit I gene (COI) of Monochamus galloprovincialis (Coleoptera, Cerambycidae) for which overlapping signals in sequencing electropherograms were observed. Comparison of full and corrected ‘ambiguities‐free’ data sets reveals the prevalence of numerous supernumerary haplotypes that deeply affect genetic diversity indices and phylogeographic patterns of this species. Slightly divergent pseudogenes were recovered in 49 of the 115 sequences. These results highlight the potential misdetection of NUMTs using current control methods and the consequences on phylogeographic structure. To test the frequency of unintended amplification of NUMTs, a cloning was performed on 15 individuals. An average of 3.72 and a maximum of six paralogous sequences with different levels of divergence were identified among individual cloned. Within individual pairwise distance between paralogs raised 1.4%. This work calls for awareness to the presence of undetected NUMTs within mitochondrial data sets, especially at infra‐specific level. 相似文献
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59.
Fotini Lamari John Katsimpris Sotiris Gartaganis Nikos K Karamanos 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1998,709(2):117
The concentrations of hyaluronan and galactosaminoglycans - i.e., chondroitin sulfate and dermatan sulfate - were measured in the aqueous humor of the eye from patients with exfoliation syndrome and from healthy persons. The glycosaminoglycans/proteoglycans were almost completely precipitated (>97%) with ethanol in the presence of dextran as carrier and, following enzymic digestion, hyaluronan and galactosaminoglycans, were quantitatively converted to Δ4,5-disaccharides. Non-degraded heparan sulfate and proteins/glycoproteins were removed by ultrafiltration using a Centricon 3 membrane. Separation and determination of hyaluronan- and galactosaminoglycan-derived Δ-disaccharides were performed by ion-suppression HPLC. For an accurate analysis in triplicate, as little as 50 μl of aqueous humor is required. Application of this method to the analysis of samples from six patients with exfoliation syndrome and three healthy persons showed that hyaluronan levels in patients (6.65–16.15 μg ml−1) were significantly higher (3–8 times) than in healthy persons (2.0–2.24 μg ml−1). There was no significant alteration in the galactosaminoglycan concentration. The obtained data open a new area in the deeper understanding of the exfoliation syndrome pathophysiology and in establishing a highly sensitivity and accurate HPLC method for its diagnosis and patient's follow-up. 相似文献
60.
Diamantopoulou A Raftogianni A Stamatakis A Alikaridis F Oitzl MS Stylianopoulou F 《PloS one》2012,7(3):e33793