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1.
Peptide aptamers have emerged as powerful new tools for molecular medicine. They can specifically bind to and functionally
inactivate a given target molecule under intracellular conditions. Typically, peptide aptamers are generated by screening
a randomized peptide expression library, displayed from the Escherichia coli thioredoxin A (TrxA) protein. Here, we transferred peptide moieties from defined TrxA-based peptide aptamers to alternative
scaffold proteins, such as the green fluorescent protein and staphylococcal nuclease. Yeast and mammalian two-hybrid assays
as well as in vitro binding analyses show that the TrxA scaffold can be a major determinant for the binding of peptide aptamers.
In addition, we demonstrate that TrxA can correctly display peptide sequences that correspond to the binding domains of natural
interaction partners. Therefore, sequence analyses of TrxA-based peptide aptamers, isolated by two-hybrid screening from randomized
expression libraries, should also be useful to find cellular binding partners for a given target protein, by homology.
Received 1 August 2002; received after revision 17 September 2002; accepted 19 September 2002
RID="*"
ID="*"Corresponding author. 相似文献
2.
ERKs are the point of divergence of PKA and PKC activation by PTHrP in human skin fibroblasts 总被引:3,自引:0,他引:3
Fortino V Torricelli C Gardi C Valacchi G Rossi Paccani S Maioli E 《Cellular and molecular life sciences : CMLS》2002,59(12):2165-2171
Parathyroid hormone-related peptide (PTHrP) receptors, coupled to trimeric G proteins, operate in most target cells through
at least three different transduction routes: Gαs-mediated stimulation of adenylylcyclase (AC), Gαq-mediated activation of
phospholipase Cβ (PLC) and mitogen-activated protein kinase (MAPK) activation. In this study we investigated the relative
role of different pathways in human skin fibroblast prolifera-tion. Using chemical inhibitors and activators of signal transduction,
we demonstrated that: (i) AC/cAMP and PLC/1,4,5 inositol triphosphate/diacylglycerol second-messenger systems are simultaneously
activated following PTHrP binding to its receptors; (ii) the mitogenic response to PTHrP derives from a balance between two
counteracting pathways – an activating route mediated by protein kinase C (PKC) and an inhibitory route mediated by protein
kinase A (PKA); (iii) PTHrP mitogenic effects are largely dependent on MAPKs, whose activity can be modulate
d by both PKA and PKC. Our results indicate that MAPKs are common targets of both transduction routes and, at the same time,
their point of divergence in mediating PTHrP dual and opposite mitogenic effects.
Received 2 August 2002; received after revision 10 September 2002; accepted 18 October 2002
RID="*"
ID="*"Corresponding author. 相似文献
3.
Melatonin regulation of antioxidant enzyme gene expression 总被引:15,自引:0,他引:15
Mayo JC Sainz RM Antoli I Herrera F Martin V Rodriguez C 《Cellular and molecular life sciences : CMLS》2002,59(10):1706-1713
Antioxidant enzymes (AOEs) are part of the primary cellular defense against free radicals induced by toxins and/or spontaneously
formed in cells. Melatonin (MLT) has received much attention in recent years due to its direct free radical scavenging and
antioxidant properties. In the present work we report that MLT, at physiological serum concentrations (≈ 1 nM), increases
the mRNA of both superoxide dismutases (SODs) and glutathione peroxidase (GPx) in two neuronal cell lines. The MLT effect
on both SODs and GPx mRNA was mediated by a de novo synthesized protein. MLT alters mRNA stability for Cu-Zn SOD and GPx.
Experiments with a short time treatment (pulse action) of MLT suggest that the regulation of AOE gene expression is likely
to be receptor mediated, because 1-h treatment with MLT results in the same response as a 24-h treatment.
Received 18 June 2002; received after revision 5 August 2002; accepted 27 August 2002
RID="*"
ID="*"Corresponding author. 相似文献
4.
5.
Kiave-Yune HoWangYin Maria Loustau Juan Wu Estibaliz Alegre Marina Daouya Julien Caumartin Sylvie Sousa Anatolij Horuzsko Edgardo D. Carosella Joel LeMaoult 《Cellular and molecular life sciences : CMLS》2012,69(23):4041-4049
The non-classical Human leukocyte antigen G (HLA-G) differs from classical HLA class I molecules by its low genetic diversity, a tissue-restricted expression, the existence of seven isoforms, and immuno-inhibitory functions. Most of the known functions of HLA-G concern the membrane-bound HLA-G1 and soluble HLA-G5 isoforms, which present the typical structure of classical HLA class I molecule: a heavy chain of three globular domains α1–α2–α3 non-covalently bound to β-2-microglobulin (B2M) and a peptide. Very little is known of the structural features and functions of other HLA-G isoforms or structural conformations other than B2M-associated HLA-G1 and HLA-G5. In the present work, we studied the capability of all isoforms to form homomultimers, and investigated whether they could bind to, and function through, the known HLA-G receptors LILRB1 and LILRB2. We report that all HLA-G isoforms may form homodimers, demonstrating for the first time the existence of HLA-G4 dimers. We also report that the HLA-G α1–α3 structure, which constitutes the extracellular part of HLA-G2 and HLA-G6, binds the LILRB2 receptor but not LILRB1. This is the first report of a receptor for a truncated HLA-G isoform. Following up on this finding, we show that the α1–α3-Fc structure coated on agarose beads is tolerogenic and capable of prolonging the survival of skin allografts in B6-mice and in a LILRB2-transgenic mouse model. This study is the first proof of concept that truncated HLA-G isoforms could be used as therapeutic agents. 相似文献
6.
Immunotolerant functions of HLA-G 总被引:9,自引:0,他引:9
Carosella ED Dausset J Rouas-Freiss N 《Cellular and molecular life sciences : CMLS》1999,55(3):327-333
7.
Corda D Hidalgo Carcedo C Bonazzi M Luini A Spanò S 《Cellular and molecular life sciences : CMLS》2002,59(11):1819-1832
Membrane fission is essential in various intracellular dissociative transport steps. The molecular mechanisms by which endocytic
vesicles detach from the plasma membrane are being rapidly elucidated. Much less is known about the fission mechanisms operating
at Golgi tubular networks; these include the Golgi transport and sorting stations, the trans-Golgi and cis-Golgi networks,
where the geometry and physical properties of the membranes differ from those at the cell surface. Here we discuss the lipid
and protein machineries that have so far been related to the fission process, with emphasis on those acting in the Golgi complex.
Received 10 May 2002; received after revision 20 June 2002; accepted 26 June 2002
RID="*"
ID="*"Corresponding author. 相似文献
8.
Bandholtz L Guo Y Palmberg C Mattsson K Ohlsson B High A Shabanowitz J Hunt DF Jörnvall H Wigzell H Agerberth B Gudmundsson GH 《Cellular and molecular life sciences : CMLS》2003,60(2):422-429
CpG motifs originating from bacterial DNA (CpG DNA) can act as danger signals for the mammalian immune system. These CpG
DNA motifs like many other pathogen-associated molecular patterns are believed to be recognized by a member of the toll-like
receptor family, TLR-9. Here we show results suggesting that heat shock protein 90 (hsp90) is also implicated in the recognition
of CpG DNA. Hsp90 was characterized as a binder to oligodeoxynucleotides (ODNs) containing CpG motifs (CpG ODNs) after several
purification steps from crude protein extracts of peripheral blood mononuclear cells. This finding was further supported by
direct binding of CpG ODNs to commercially available human hsp90. Additionally, immunohistochemistry studies showed redistribution
of hsp90 upon CpG ODN uptake. Thus, we propose that hsp90 can act as a ligand transfer molecule and/or play a central role
in the signaling cascade induced by CpG DNA.
Received 18 December 2002; accepted 6 January 2002
RID="*"
ID="*"Corresponding author. B. Agerberth and G. H. Gudmundsson contributed equally to this work. 相似文献
9.
Specialised copper sites have been recruited during evolution to provide long-range electron transfer reactivity and oxygen
binding and activation in proteins destined to cope with oxygen reactivity in different organisms. Ceruloplasmin is an ancient
multicopper oxidase evolved to insure a safe handling of oxygen in some metabolic pathways of vertebrates. The presently available
knowledge of its structure provides a glimpse of its plasticity, revealing a multitude of binding sites that point to an elaborate
mechanism of multifunctional activity. Ceruloplasmin represents an example of a 'moonlighting' protein that overcomes the
one gene-one structure-one function concept to follow the changes of the organism in its physiological and pathological conditions.
Received 19 February 2002; received after revision 29 March 2002; accepted 2 April 2002
RID="*"
ID="*"Corresponding author. 相似文献
10.
Species-specific cell adhesion in marine sponges is mediated by a new family of modular proteoglycans whose general supramolecular
structure resembles that of hyalectans. However, neither their protein nor their glycan moieties have significant sequence
homology to other proteoglycans, despite having protein subunits equivalent to link proteins and to proteoglycan monomer core
proteins, and glycan subunits equivalent to hyaluronan and to the glycosaminoglycans of hyalectans. In some species, these
molecular components are assembled into a structure with a circular core formed by the link protein- and hyaluronan-like subunits.
Besides their involvement in cell adhesion, these sponge proteoglycans, for which we propose the term spongicans, participate
in signal transduction processes and are suspected to play a role in sponge self-nonself recognition. Their in vivo roles
and the mild methods used to purify large amounts of functionally active spongicans make them ideal models to study the functions
and possible new applications of proteoglycans in biomedical research.
Received 21 May 2002; received after revision 5 July 2002; accepted 10 July 2002
RID="*"
ID="*"Corresponding author. 相似文献
11.
Carosella ED Gregori S Rouas-Freiss N LeMaoult J Menier C Favier B 《Cellular and molecular life sciences : CMLS》2011,68(3):353-368
The non-classical HLA class I molecule HLA-G was initially shown to play a major role in feto–maternal tolerance. Since this
discovery, it has been established that HLA-G is a tolerogenic molecule which participates to the control of the immune response.
In this review, we summarize the recent advances on (1) the multiple structures of HLA-G, which are closely associated with
their role in the inhibition of NK cell cytotoxicity, (2) the factors that regulate the expression of HLA-G and its receptors,
(3) the mechanism of action of HLA-G at the immunological synapse and through trogocytosis, and (4) the generation of suppressive
cells through HLA-G. Moreover, we also review recent findings on the non-immunological functions of HLA-G in erythropoiesis
and angiogenesis. 相似文献
12.
Guthmann F Maehl P Preiss J Kolleck I Rüstow B 《Cellular and molecular life sciences : CMLS》2002,59(11):1999-2003
Glycoprotein IV (FAT/CD36) has been shown to be phosphorylated by a cAMP-dependent, platelet membrane-bound ectokinase. In
this study, we demonstrate that ectophosphorylation of FAT/CD36 regulates initial palmitate uptake. This is the first time
that short-term regulation of the activity of a long-chain fatty acid carrier could be shown. Phosphorylation of FAT/CD36
was paralleled by a significant decrease in initial palmitate uptake by morphologically and functionally intact platelets.
Maximum inhibition of palmitate uptake was achieved at 0.5 nM extracellular ATP, being significantly decreased to 72% compared
to the control. Inhibition of palmitate uptake was abolished by co-incubation with the specific protein kinase A inhibitor
peptide PKI or with β,γ-methylene-ATP, and was reversible upon addition of alkaline phosphatase. An extracellular ATP concentration
above 5 μM completely prevented the ectophosphorylation-mediated inhibition of palmitate uptake. We conclude that FAT/CD36-mediated
palmitate uptake by human platelets is short-term regulated via cAMP-dependent ectophosphorylation of FAT/CD36.
Received 18 July 2002; received after revision 29 August 2002; accepted 19 September 2002
RID="*"
ID="*"Corresponding author. 相似文献
13.
Penkowa M Espejo C Martínez-Cáceres EM Montalban X Hidalgo J 《Cellular and molecular life sciences : CMLS》2003,60(1):185-197
Metallothioneins I+II (MT-I+II) are antioxidant, neuroprotective factors. We previously showed that MT-I+II deficiency during
experimental autoimmune encephalomyelitis (EAE) leads to increased disease incidence and clinical symptoms. Moreover, the
inflammatory response of macrophages and T cells, oxidative stress, and apoptotic cell death during EAE were increased by
MT-I+II deficiency. We now show for the first time that demyelination and axonal damage are significantly increased in MT-I+II
deficient mice during EAE. Furthermore, oligodendroglial regeneration, growth cone formation, and tissue repair including
expression of trophic factors were significantly reduced in MT-I+II-deficient mice during EAE. Accordingly, MT-I+II have protective
and regenerative roles in the brain.
Received 31 October 2002; received after revision 23 November 2002; accepted 26 November 2002
RID="*"
ID="*"Corresponding author. M. Penkowa and C. Espejo contributed equally to this paper. 相似文献
14.
Opposite actions of testosterone and progesterone on UCP1 mRNA expression in cultured brown adipocytes 总被引:3,自引:0,他引:3
Rodriguez AM Monjo M Roca P Palou A 《Cellular and molecular life sciences : CMLS》2002,59(10):1714-1723
The brown adipose tissue (BAT) thermogenic response to diet-induced obesity and cold has been found to be gender dependent.
In the present work, we aimed to investigate the effects of the main physiological male and female sex hormones, i.e. testosterone,
progesterone and 17-β-estradiol, on the expression of uncoupling protein 1 (UCP1) – the main mediator of BAT thermogenesis
– and on UCP2 and lipid accumulation in rodent brown adipocytes differentiated in culture. Testosterone-treated cells showed
fewer and smaller lipid droplets than control cells and a dose-dependent inhibition of UCP1 mRNA expression, under adrenergic
stimulation by norepinephrine (NE). These effects were reverted by the androgen receptor antagonist flutamide, suggesting
they are dependent, at least in part, on the androgen receptor. Progesterone- and 17-β-estradiol-treated cells showed more
and larger lipid droplets and progesterone stimulated NE-induced UCP1 mRNA expression at the lower concentration tested, but
not at higher concentrations, suggesting that for brown adipocytes, this hormone is dose dependent. 17-β-Estradiol did not
have any remarkable effect either on UCP1 or UCP2 mRNA expression. Interestingly, the specific progesterone receptor antagonist
RU486 induced UCP1 and UCP2 mRNAs, including UCP1 mRNA expression in non-NE-treated brown adipocytes, suggesting a profound
effect of this anti-progestagen on brown adipocyte thermogenic capacity. Thus, are conclude that testosterone, 17-β-estradiol,
progesterone and RU486 have distinct actions on brown adipocytes, thus modulating UCP1 and UCP2 mRNA expression and/or lipid
accumulation, and that sex hormones are factors that may explain in part the gender-dependent BAT thermogenic response.
Received 24 June 2002; received after revision 20 August 2002; accepted 26 August 2002
RID="*"
ID="*"Corresponding author. 相似文献
15.
Lesport E Baudhuin J Sousa S LeMaoult J Zamborlini A Rouas-Freiss N Carosella ED Favier B 《Cellular and molecular life sciences : CMLS》2011,68(20):3385-3399
Vγ9Vδ2 T cells play a crucial role in the antitumoral immune response through cytokine production and cytotoxicity. Although
the expression of the immunomodulatory molecule HLA-G has been found in diverse tumors, its impact on Vγ9Vδ2 T-cell functions
remains unknown. Here we showed that soluble HLA-G inhibits Vγ9Vδ2 T-cell proliferation without inducing apoptosis. Moreover,
soluble HLA-G inhibited the Vγ9Vδ2 T-cell production of IFN-γ induced by phosphoantigen stimulation. The reduction in Vγ9Vδ2
T-cell IFN-γ production was also induced by membrane-bound or soluble HLA-G expressed by tumor cell lines. Finally, primary
tumor cells inhibited Vγ9Vδ2 T-cell proliferation and IFN-γ production through HLA-G. In this context, HLA-G impaired Vγ9Vδ2
T-cell cytotoxicity by interacting with ILT2 inhibitory receptor. These data demonstrate that HLA-G inhibits the anti-tumoral
functions of Vγ9Vδ2 T cells and imply that treatments targeting HLA-G could optimize Vγ9Vδ2 T-cell-mediated immunotherapy
of cancer. 相似文献
16.
Identification of the bioactive peptide PEC-60 in brain 总被引:1,自引:0,他引:1
Norberg A Gruber S Angelucci F Renlund S Wadensten H Efendic S Ostenson CG Jörnvall H Sillard R Mathé AA 《Cellular and molecular life sciences : CMLS》2003,60(2):378-381
PEC-60 is a 60-residue peptide originally isolated from pig intestine. It inhibits glucose-induced insulin secretion from
perfused pancreas in a hormonal manner and also has biological activity in the immune system. PEC-60-like immunoreactive material
has been reported in catecholamine neurons of the central and peripheral nervous systems, but the peptide has not been identified
from that material. We have now isolated PEC-60 from pig and rat brains with a method that combines column purification procedures
with the specificity of a radioimmunoassay and the sensitivity of mass spectrometry to directly identify the peptide. The
results show that PEC-60, like many other peptides, is expressed in the gastrointestinal tract and the central nervous system.
The specific regional brain distribution and interaction with classical neurotransmitters raise the possibility that PEC-60may
play a role in the central nervous system disorders involving dopamine dysregulation.
Received 6 December 2002; received after revision 10 December 2002; accepted 11 December 2002
RID="*"
ID="*"Corresponding author. 相似文献
17.
Microtubule associated protein tau binds to double-stranded but not single-stranded DNA 总被引:3,自引:0,他引:3
Hua Q He RQ Haque N Qu MH del Carmen Alonso A Grundke-Iqbal I Iqbal K 《Cellular and molecular life sciences : CMLS》2003,60(2):413-421
Tau, a major microtubule-associated protein of the neuron, which is known to promote the assembly of and to stabilize microtubules,
has also been seen associated with chromatin in neuronal cell lines, but its role in this subcellular compartment is still
unknown. In this study, the binding of tau to DNA was investigated using the electrophoretic mobility shift assay. Using polynucleotide
as probe, we found that tau bound to double-stranded but not to single-stranded DNA. Formation of tau-polynucleotide complex
was disrupted by alkaline pH and a high concentration of NaCl, but was not affected by dithiothreitol. Electron microscopy
revealed that the protein associated with the nucleic acid in a necklacelike manner. DNA-cellulose chromatography and radioimmunodot-blot
analyses showed that calf thymus histones VI-S, VII-S and VIII-S could replace both recombinant human brain tau352 (tau-23) and tau441 (tau-40) from DNA. Thus, tau appears to bind to DNA reversibly in the presence of histones.
Received 24 November 2002; received after revision 28 December 2002; accepted 30 December 2002
RID="*"
ID="*"Corresponding author. 相似文献
18.
Gömez-Casado E Martínez-Lasot J Castro MJ Morales P Trápaga J Berciano M Lowy E Arnaiz-Villena A 《Cellular and molecular life sciences : CMLS》1999,56(3-4):356-362
HLA-E and -G genes show a restricted polymorphism encoding for molecules whose variability is limited at the peptide binding
site. Fourteen alleles that give rise to only three productive proteins for HLA-G (*0101, *0103 and *0104) and five alleles
with three different proteins for HLA-E (*0101, *0102 and *0103) have been described. Expression of these molecules is low
and found in many tissues for HLA-E; HLA-G protein is expressed in extravillous trophoblast cells and thymic epithelium. Molecular
studies have shown how HLA-G and HLA-E bind to natural killer (NK) cells immunoglobulin and lectin-type inhibitory receptors.
HLA-E may act as a sentinel of the cell; if classical class I and HLA-G are being expressed, HLA-E molecules may reach the
cell surface and inhibit the lysis by NK cells. Most findings are consistent with the hypothesis that HLA-E and -G proteins
may be tolerogenic molecules at either the T-cell receptor (TcR) (inflammation, graft rejection) or NK level, switching off
cells which usually attack foreign (including foetus) or self (autoimmune) antigens. A low HLA-E and -G polymorphism is observed
in humans, and their allele frequencies are mostly homogeneous in the populations tested so far. Many studies to detect these
alleles are now being performed in isolated populations and also in pregnancy-associated pathologies. In the present paper,
standard and detailed techniques to detect HLA-E and -G DNA polymorphism are reported and discussed.
Received 14 July 1999; received after revision 25 August 1999; accepted 25 August 1999 相似文献
19.
Retinoic acid modulates gap junctional intercellular communication in hepatocytes and hepatoma cells 总被引:3,自引:0,他引:3
Ara C Massimi M Devirgiliis Conti L 《Cellular and molecular life sciences : CMLS》2002,59(10):1758-1765
Gap junctional communication permits the direct exchange of small molecules and ions and has been implicated in tissue homeostasis/metabolite
exchange. The lack of gap junctional intercellular communication (GJIC) plays important roles in the promotion and progression
of carcinogenesis. In the present study, we demonstrate that treatment of human hepatoma Hep G2 cells with retinoic acid (RA)
results in increased amounts and phosphorylation of connexins, their stabilisation in plasma membrane plaques and enhanced
GJIC. In cultured fetal hepatocytes, which represent a non-transformed, proliferating and incompletely differentiated liver
system, the effects of RA are limited to the establishment of connexin in areas of cell-cell contact and the improvement of
GJIC. This suggests that modulation of cell-cell channel communication by RA occurs differently in these two experimental
models: while RA is able to revert cell transformation in Hep G2 cells, in fetal hepatocytes it may induce the expression
of a more differentiated phenotype.
Received 19 June 2002; received after revision 29 July 2002; accepted 8 August 2002
RID="*"
ID="*"Corresponding author. 相似文献
20.
Rizzo R Vercammen M van de Velde H Horn PA Rebmann V 《Cellular and molecular life sciences : CMLS》2011,68(3):341-352
The nonclassical HLA-G molecule is a trophoblast-specific molecule present in almost every pregnancy. It differs from classical
HLA class I molecules by the low degree of allelic variants and the high diversity of protein structures. HLA-G is reported
to be a tolerogenic molecule that acts on cells of both innate and adaptive immunity. At the maternal–fetal interface HLA-G
seems to be responsible largely for the reprogramming of local maternal immune response. This review will focus on the HLA-G
gene expression profile in pregnancy, in preimplantation embryos, and in human embryonic stem cells with emphasis on the structural
diversity of the HLA-G protein and its potential functional and diagnostic implications. 相似文献