共查询到20条相似文献,搜索用时 31 毫秒
1.
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
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ID="*"Corresponding author. 相似文献
2.
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
3.
Recent discoveries revealing that carbohydrate modifications play critical roles in a wide variety of biological processes
have brought wide recognition to the field of glycobiology. Growing attention has focused on the function of unusual O-linked carbohydrate modifications such as O-fucose. O-fucose modifications have been described in several different protein contexts, including epidermal growth factor-like repeats
and thrombospondin type 1 repeats. The O-fucose modifications on thrombospondin type 1 repeats have only recently been described, but the site of modification occurs
in a region proposed to play a role in cell adhesion. O-fucose modifications on epidermal growth factor-like repeats have been described as important players in several signal transduction
systems. For instance, Notch, a cell-surface signaling receptor required for many developmental events, bears multiple O-fucose saccharides on the epidermal growth factor-like repeat of its extracellular domain. The O-fucose moieties serve as a substrate for the β1,3 N-acetylglucosaminyltransferase activity of Fringe, a known modifier of Notch function. The alteration of O-fucose structures by Fringe influences the ability of Notch ligands to activate the receptor and provides a means to regulate
Notch signaling. Thus, O-fucose and Fringe provide a clear example of how carbohydrate modifications can have direct functional consequences on the
proteins they modify.
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4.
Di Francesco AM Ruggiero A Riccardi R 《Cellular and molecular life sciences : CMLS》2002,59(11):1914-1927
Oxaliplatin (Eloxatine) is a third-generation platinum compound which has shown a wide antitumour effect both in vitro and
in vivo, a better safety profile than cisplatin and a lack of cross-resistance with cisplatin and carboplatin. In this scenario,
oxaliplatin may represent an innovative and challenging drug extending the antitumour activity in diseases such as gastrointestinal
cancer that are not usually sensitive to these coordination complexes. Oxaliplatin has a non-hydrolysable diaminocyclohexane
(DACH) carrier ligand which is maintained in the final cytotoxic metabolites of the drug. Like cisplatin, oxaliplatin targets
DNA producing mainly 1,2-GG intrastrand cross-links. The cellular and molecular aspects of the mechanism of action of oxaliplatin
have not yet been fully elucidated. However, the intrinsic chemical and steric characteristics of the DACH-platinum adducts
appear to contribute to the lack of cross-resistance with cisplatin. To date, mismatch repair and replicative bypass appear
to be the processes most likely involved in differentiating the molecular responses to these agents.
Received 15 March 2002; received after revision 13 May 2002; accepted 21 May 2002
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ID="*"Corresponding author. 相似文献
5.
Proteins of thermophilic organisms are adapted to remain well structured and functional at elevated temperatures. Nevertheless
like their 'cousins' that reside at medium temperatures, they require the assistance of molecular chaperones to fold properly
and prevent aggregation. This review compares structural and functional properties of the DnaK/ClpB systems of Thermus thermophilus and, mainly, Escherichia coli (DnakTth and DnakEco). Many elemental properties of these systems remain conserved. However, in addition to a general increase of the thermal
stability of its components, the DnakTth system shows profound differences in its regulation, and genetic as well as oligomeric organization. Whether these differences
are unique or represent general strategies of adaptation to life at elevated temperatures remains to be clarified.
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6.
Macpherson AJ Martinic MM Harris N 《Cellular and molecular life sciences : CMLS》2002,59(12):2088-2096
There is an immense load of non-pathogenic commensal bacteria in the distal small intestine and the colon of mammals. The
physical barrier that prevents penetration (translocation) of these organisms into the body is a simple epithelium comprised
of the single enterocyte/colonocyte cell layer with its overlying mucus. In this review, we discuss the roles of intestinal
T cells in initiating and regulating innate and adaptive mucosal immune responses of the mucosal immune system that avoid
or limit penetration of the commensal intestinal bacteria.
Received 9 August 2002; accepted 9 September 2002
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ID="*"Corresponding author. 相似文献
7.
Protein misfolding and disease: the case of prion disorders 总被引:2,自引:0,他引:2
Recent findings strongly support the hypothesis that diverse human disorders, including the most common neurodegenerative
diseases, arise from misfolding and aggregation of an underlying protein. Despite the good evidence for the involvement of
protein misfolding in disease pathogenesis, the mechanism by which protein conformational changes participate in the disease
is still unclear. Among the best-studied diseases of this group are the transmissible spongiform encephalopathies or prion-related
disorders, in which misfolding of the normal prion protein plays a key role in the disease. In this article we review recent
data on the link between prion protein misfolding and the pathogensis of spongiform encephalopathies.
Received 15 July 2002; received after revision 19 August 2002; accepted 23 August 2002
RID="*"
ID="*"Corresponding author. 相似文献
8.
Neuropeptide Y: the universal soldier 总被引:13,自引:0,他引:13
The peptidic neurotransmitter neuropeptide Y (NPY) has received great attention because it has been implicated in the regulation
of several organ systems. In particular, NPY is involved in the regulatory loops that control food intake in the hypothalamus
and appears also to be important for regulating the activity of neuroendocrine axes under poor metabolic conditions. Furthermore,
NPY exerts vasoconstrictive action on the vasculature and potentiates the actions of many other vasoconstrictors. In addition,
it was demonstrated to have trophic properties and could therefore contribute to cardiovascular remodeling. These various
effects plus a number of others make NPY an attractive target for the potential treatment of human diseases, such as obesity,
metabolic disorders, hypertension and heart failure.
Received 17 July 2002; received after revision 7 November 2002; accepted 29 November 2002
RID="*"
ID="*"Corresponding author. 相似文献
9.
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
10.
Translocation of conjugative transposons proceeds via excision of the element to generate a circular molecule that can then
integrate into a new site, which can be in the same or a different cell. This review summarises some of the different mechanisms
used for excision and integration of conjugative transposons.
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ID="*"Corresponding author. 相似文献
11.
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
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ID="*"Corresponding author. 相似文献
12.
This review begins with a general presentation of the new paradigm of drug discovery, with its emphasis on the rapid identification
and elimination of compounds with unsuitable physicochemical and pharmacokinetic properties. The focus of the paper is on
the various experimental methods used to determine such key physicochemical properties as ionization, lipophilicity and distribution
in isotropic and anisotropic systems, solubility, and permeability across artificial membranes. Both traditional and high-throughput
methods are presented and their limits highlighted. The text concludes with the trade-off between quantity/speed in high-throughput
screening techniques versus greater data quality in the more labor-intensive methods.
Received 23 April 2002; received after revision 25 June 2002; accepted 11 July 2002
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ID="*"Corresponding author. 相似文献
13.
Moreau P Rousseau P Rouas-Freiss N Le Discorde M Dausset J Carosella ED 《Cellular and molecular life sciences : CMLS》2002,59(9):1460-1466
Data are presented on the intracellular trafficking of HLA-G protein, taking the unique features of this non-classical molecule
into consideration: the existence of seven isoforms resulting from alternative splicing (HLA-G1 to G7), and reduced tail length
compared with HLA class I antigens. Biochemical studies and analysis of viral strategies for escaping the host immune system
led to the demonstration that (i) both the membrane-bound (HLA-G1) and the soluble (HLA-G5) forms of the molecule require
peptide association for cell surface expression, using TAP-dependent or TAP-independent pathways; (ii) peptide loading onto
the HLA-G protein plays a critical role in controlling the quality of the molecule reaching the cell surface; (iii) surface
expression of truncated HLA-G molecules is possible, and (iv) HLA-G expression may be restricted to soluble HLA-G5. These
data reveal that HLA-G presents specific cell trafficking pathways and strongly support the contention that the primary function
of HLA-G is as of an inhibitor ligand for immune-competent cells.
Received 4 June 2002; accepted 2 July 2002
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ID="*"Corresponding author. 相似文献
14.
Galactofuranose-containing glycoconjugates are present in numerous microbes, many of which are pathogenic for humans. Metabolic
aspects of the monosaccharide have proven difficult to elucidate, because galactofuranose metabolites and glycoconjugates
are relatively unstable during analyses. Recent advances in biochemical and genetic approaches, however, have facilitated
a better understanding of galactofuranose metabolism. This review summarizes our current information on its metabolism and
a few selected glycoconjugates containing this furanose.
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ID="*"Corresponding author. 相似文献
15.
Netrins and netrin receptorsRID="†"ID="†" Review 总被引:5,自引:0,他引:5
Livesey FJ 《Cellular and molecular life sciences : CMLS》1999,56(1-2):62-68
The formation of precise connections between neurons and their targets during development is dependent on extracellular guidance cues that allow growing axons to navigate to their targets. One family of such guidance molecules. conserved across all species examined, is that of the netrin/UNC-6 proteins. Netrins act to both attract and repel the growing axons of a broad range of neuronal cell types during development and are also involved in controling neuronal cell migration. These actions are mediated by specific receptor complexes containing either the colorectal cancer (DCC) or neogenin protein, in the case of the attractive receptor, or UNC-5-related proteins, in the case of the repellent receptor. Recent work has identified a key role for intracellular cyclic nucleotide levels in regulating the nature of the response of the growing axon to netrins as either attractive or repulsive. Netrin-DCC signaling has also been shown to regulate cell death in epithelial cells in vitro, raising the interesting possibility that netrins may also regulate cell death in the developing nervous system. 相似文献
16.
A role for <Emphasis Type="Italic">N</Emphasis>-acetylglucosamine as a nutrient sensor and mediator of insulin resistance 总被引:4,自引:0,他引:4
The ability to regulate energy balance at both the cellular and whole body level is an essential process of life. As western
society has shifted to a higher caloric diet and more sedentary lifestyle, the incidence of type 2 diabetes (non-insulin-dependent
diabetes mellitus) has increased to epidemic proportions. Thus, type 2 diabetes has been described as a disease of 'chronic
overnutrition'. There are abundant data to support the relationship between nutrient availability and insulin action. However,
there have been multiple hypotheses and debates as to the mechanism by which nutrient availability modulates insulin signaling
and how excess nutrients lead to insulin resistance. One well-established pathway for nutrient sensing is the hexosamine biosynthetic
pathway (HSP), which produces the acetylated aminosugar nucleotide uridine 5′-diphospho-N-acetylglucosamine (UDP-GlcNAc) as its end product. Since UDP-GlcNAc is the donor substrate for modification of nucleocytoplasmic
proteins at serine and threonine residues with N-acetylglucosamine (O-GlcNAc), the possibility of this posttranslational modification serving as the nutrient sensor has been proposed. We have
recently directly tested this model in adipocytes by examining the effect of elevated levels of O-GlcNAc on insulin-stimulated glucose uptake. In this review, we summarize the existing work that implicates the HSP and O-GlcNAc modification as nutrient sensors and regulators of insulin signaling.
RID="*"
ID="*"Corresponding author. 相似文献
17.
Genes involved in breast cancer metastasis to bone 总被引:12,自引:0,他引:12
Metastasis to bone occurs frequently in advanced breast cancer and is accompanied by debilitating skeletal complications.
Current treatments are palliative and new therapies that specifically prevent the spread of breast cancer to bone are urgently
required. While our understanding of interactions between breast cancer cells and bone cells has greatly improved, we still
know little about the molecular determinants that regulate specific homing of breast cancer cells to the bone. In this review,
we focus on genes that have been implicated in migration and adhesion of breast cancer cells to bone, as well as genes that
promote tumor cell proliferation in the bone microenvironment. In addition, the review discusses new technologies, including
better animal models, that will further assist with the identification of the molecular determinants of bone metastasis and
will guide the development of new therapies.
Received 25 January 2002; received after revision 27 March 2002; accepted 5 April 2002
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ID="*"Corresponding author. 相似文献
18.
Johansson S Gullbo J Lindholm P Ek B Thunberg E Samuelsson G Larsson R Bohlin L Claeson P 《Cellular and molecular life sciences : CMLS》2003,60(1):165-175
Four novel proteins (phoratoxins C–F) have been isolated from the North American mistletoe Phoradendron tomentosum. The amino acid sequences of these phoratoxins were determined unambiguously using a combination of Edman degradation and
trypsin enzymatic digestion, and by electrospray ionization tandem mass spectrometry sequencing. Phoratoxins C, E and F consist
of 46 amino acid residues; and phoratoxin D of 41. All proteins had six cysteines, similar to the earlier described phoratoxins
A and B, which are thionins. The cytotoxicity of each protein was evaluated in a human cell line panel that represented several
cytotoxic drug-resistance mechanisms. For the half-maximal inhibitory concentrations (IC50 values) of the different cell lines in the panel, correlation with those of standard drugs was low. The most potent cytotoxic
phoratoxin C was further tested on primary cultures of human tumor cells from patients. The solid tumor samples from breast
cancer cells were 18 times more sensitive to phoratoxin C than the tested hematological tumor samples.
Received 30 September 2002; received after revision 28 October 2002; accepted 7 November 2002
RID="*"
ID="*"Corresponding author. 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
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ID="*"Corresponding author. 相似文献
20.
Neurotrophins are a family of structurally and functionally related neurotrophic factors which, in mammals, include: nerve
growth factor, brain-derived neurotrophic factor, neurotrophin-3 (NT-3), and NT-4/5. In addition to their canonical role in
promoting neuronal survival, these molecules appear to regulate multiple aspects of the development of the nervous system
in vertebrates, including neuronal differentiation, axon elongation and target innervation, among others. Actions of neurotrophins
and of their receptors in vivo are being analyzed by loss-of-function or gain-of-function experiments in mice. Here, we review
the phenotypes of the primary sensory system in these mutant mouse strains and the different strategies specifically involved
in the regulation of neuronal survival by neurotrophins in this portion of the nervous system.
Received 10 December 2001; received after revision 11 May 2002; accepted 13 May 2002
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ID="*"Corresponding author. 相似文献