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1.
L. Adorini 《Cellular and molecular life sciences : CMLS》1999,55(12):1610-1625
Interleukin 12 (IL-12) is a heterodimeric cytokine produced primarily by antigen-presenting cells (APCs) which plays a key
role in promoting type 1 T helper cell (Th1) responses. The powerful activity of IL-12 requires tight control, which is exerted
at various levels. Primary control is exerted on IL-12 production by APCs, a major factor driving the response towards the
Th1 or Th2 phenotype. Another level of control regulates expression of the IL-12 receptor (IL-12R), which is composed of two
subunits, β1 and β2. The IL-12R β2 subunit has signal-transducing capacity and modulation of its expression is central to
the regulation of IL-12 responsiveness. Endogenous IL-12 plays an important role in host defense against infection by a variety
of intracellular pathogens. Its Th1-promoting activity, however, also favors Th1-mediated immunopathology and, in particular,
the induction of Th1-mediated autoimmune diseases.
Received 15 January 1999; received after revision 11 March 1999; accepted 16 March 1999 相似文献
2.
H. S. Lee Y. S. Kim S. B. Kim B. E. Choi B. H. Woo K. C. Lee 《Cellular and molecular life sciences : CMLS》1999,55(4):679-682
A mistletoe lectin was isolated from water extracts of Korean mistletoe, a subspecies of Viscum album, grown on Quercus mongolica using CM-Sepharose chromatography followed by an affinity chromatography on a concanavalin A-Sepharose column. The compound
proved to be a mistletoe lectin II with D-galactose and N-acetyl-D-galactosamine specificity. Matrix-assisted laser desorption time-of-flight mass spectroscopy showed it to have an
average molecular mass of 62.7 kDa and to consist of two subunits of 30.6 kDa and 32.5 kDa. It was a basic protein with isoelectric
points of 9.4 and 9.6 by capillary isoelectric focusing and was cytotoxic to Molt4 cell.
Received 17 November 1998; received after revision 3 March 1999; accepted 3 March 1999 相似文献
3.
The role of hsp70 in protection and repair of luciferase activity in vivo; experimental data and mathematical modelling 总被引:1,自引:0,他引:1
J. E. M. Souren F. A. C. Wiegant R. Van Wijk 《Cellular and molecular life sciences : CMLS》1999,55(5):799-811
The stably transfected rat cell line HR24 expressing high levels of the inducible human hsp70 and its parental cell line
Rat-1 were used for in vivo studies to analyse the role of hsp70 during thermal protein denaturation and the subsequent renaturation.
In order to monitor denaturation and renaturation of a cellular protein in vivo, both cell lines were transiently transfected
with firefly luciferase (Luc). The continuous monitoring of Luc activity during and after heat stress allowed a detailed analysis
of the inactivation and reactivation kinetics in cells grown in monolayers. The aim of these studies was to distinguish a
protective effect of increased hsp70 levels during heat shock-induced protein inactivation from a stimulation of reactivation.
In this paper we show that in cells that are stably transfected with hsp70, thermal Luc inactivation decreased, and subsequent
reactivation yielded higher activity levels, compared with the parental cells. The difference in early inactivation kinetics
observed in the two cell lines suggests an immediate effect of the presence of an extra amount of hsp70 on enzyme inactivation.
Using different mathematical models, the heat-induced inactivation and reactivation kinetics was compared with simulations
of denaturation and renaturation. It is concluded that the model in which it is assumed that hsp70 is able to interact with
partially denatured proteins, which did not yet lose their enzymatic activity, most optimally explains the experimental observations.
Received 2 December 1998; received after revision 19 February 1999; accepted 18 March 1999 相似文献
4.
L. Fanuel I. Thamm V. Kostanjevecki B. Samyn B. Joris C. Goffin J. Brannigan J. Van Beeumen J. M. Frère 《Cellular and molecular life sciences : CMLS》1999,55(5):812-818
Two new enzymes which hydrolyse D-alanyl-p-nitroanilide have been detected in Ochrobactrum anthropi LMG7991 extracts. The first enzyme, DmpB, was purified to homogeneity and found to be homologous to the Dap protein produced
by O. anthropi SCRC C1-38 (ATCC49237). The second enzyme, DmpA, exhibits a similar substrate profile when tested on p-nitroanilide derivatives
of glycine and L/D-alanine, but the amounts produced by the Ochrobactrum strain were not sufficient to allow complete purification. Interestingly, the DmpA preparation also exhibited an L-aminopeptidase
activity on the tripeptide L-Ala-Gly-Gly but it was not possible to be certain that the same protein was responsible for both
p-nitroanilide and peptide hydrolysing activities. The gene encoding the DmpA protein was cloned and sequenced. The deduced
protein sequence exhibits varying degrees of similarity with those corresponding to several open reading frames found in the
genomes of other prokaryotic organisms, including Mycobacteria. None of these gene products has been isolated or characterised,
but a tentative relationship can be proposed with the NylC amidase from Flavobacterium sp. K172.
Received 7 December 1998; received after revision 15 March 1999; accepted 22 March 1999 相似文献
5.
Receptor binding, internalization, and retrograde transport of neurotrophic factors 总被引:15,自引:0,他引:15
This review deals with the receptor interactions of neurotrophic factors, focusing on the neurotrophins of the nerve growth
factor (NGF) family, the glial cell derived neurotrophic factor (GDNF) family, and the ciliary neurotrophic factor (CNTF)
family. The finding that two proteins, p75NTR and Trk, act as receptors for NGF in neurons generated the discovery of other neurotrophic factors/receptor families and
has enhanced our understanding of the development, survival, regeneration, and degeneration of the nervous system. The kinetics
of binding, the structure of the ligand-receptor complex, and the mechanism of retrograde transport of the neurotrophins are
discussed in detail and compared to information available on the GDNF and CNTF families. Each neurotrophic factor family,
i.e., NGF, GDNF, and CNTF, has a set of receptors with specificity for individual members of the family and a common receptor
without member specificity that, in some families, generates the cellular signal and retrograde transport. 相似文献
6.
Bataille D Héron L Virsolvy A Peyrollier K LeCam A Gros L Blache P 《Cellular and molecular life sciences : CMLS》1999,56(1-2):78-84
ATP-dependent potassium (KATP) channels occupy a key position in the control of insulin release from the pancreatic β cell since they couple cell polarity
to metabolism. These channels close when more ATP is produced via glucose metabolism. They are also controlled by sulfonylureas,
a class of drugs used in type 2 diabetic patients for triggering insulin secretion from β cells that have lost part of their
sensitivity to glucose. We have demonstrated the existence of endogenous counterparts to sulfonylureas which we have called
‘endosulfines.’ In this review, we describe the discovery, isolation, cloning, and biological features of the high-molecular-mass
form, α-endosulfine, and discuss its possible role in the physiology of the β cell as well as in pathology.
Received 1 February 1999; received after revision 26 March 1999; accepted 26 March 1999 相似文献
7.
Apolipoprotein E (apoE) ɛ4 allele is a genetic risk factor for late-onset familial and sporadic Alzheimer’s disease (AD).
In the central nervous system, apoE is secreted mainly by astrocytes as a constituent of high-density lipoproteins. A recent
study using apoE knockout mice provided strong evidence that apoE promotes cerebral deposition of amyloid β protein (Aβ).
However, no clear explanation of the pathogenesis of apoE-induced AD has been provided. Here we discuss two possible mechanisms
by which apoE might enhance Aβ deposition. One is the intracellular pathway in which apoE is internalized by neurons and induces
lysosomal accumulation of Aβ and amyloidogenic APP (amyloid precursor protein) fragments, leading to neuronal death. The other
is the extracellular pathway in which apoE-containing lipoproteins are trapped by Aβ1–42 deposits mobilizing soluble Aβ peptides
and consequently enlarge amyloid plaques. These two mechanisms may operate at different stages of AD pathogenesis and suggest
a chaperone-like function for the apoE molecule.
Received 4 February 1999; received after revision 9 April 1999; accepted 23 April 1999 相似文献
8.
Botulinum toxin as a carrier for oral vaccines 总被引:1,自引:0,他引:1
Simpson LL Maksymowych AB Kiyatkin N 《Cellular and molecular life sciences : CMLS》1999,56(1-2):47-61
Botulinum toxin is an unusually potent substance that acts on the nervous system to produce the clinical outcome of flaccid
paralysis. To produce this effect, the toxin ordinarily proceeds through two separate but essential sequences of events. During
the first, the toxin is ingested, it traverses a portion of the gastrointestinal system and then it is transcytosed from the
lumen of the gut to the general circulation. During the second, circulating toxin binds to peripheral cholinergic nerve endings,
it is endocytosed and then it acts as a metalloendoprotease to cleave polypeptides that are essential for exocytosis. Although
botulinum toxin is antigenic, it ordinarily does not evoke an immune response during or after cases of oral poisoning. This
is due to the fact that the dose of toxin that produces flaccid paralysis—and potentially death—is less than the dose needed
to evoke an antibody response. In the recent past, the techniques of molecular biology have been used to generate an expression
product of botulinum toxin that retains the ability to escape the gut and reach the general circulation, retains the ability
to evoke an immune response, but has lost the ability to produce neurotoxicity. This modified toxin may have two clinical
applications. The expression product itself may have utility as an oral vaccine against botulism. Beyond this, the modified
toxin, or a truncation mutant of the toxin, may have utility as a carrier in the construction of other oral vaccines. Both
potential applications could lead to the expression of oral vaccines in common foods.
Received 29 December 1998; received after revision 22 March 1999; accepted 24 March 1999 相似文献
9.
The study of Drosophila melanogaster by a combination of forward genetics with specific mutants, and reverse genetics, in which a given gene is expressed in an
appropriate brain area to test its effect on behavior, provides a unique opportunity to explore the causal relationship between
a particular gene, its function in the cell and the behavioral outcome at the organismic level. Enhanced male-to-male courtship
has been shown to occur as a result of mutations in several different genes. For example, the Voila mutant exhibits intense GAL4 reporter expression in the tarsal gustatory sensilla, suggesting the importance of tapping by
a male on the female abdomen with his forelegs. Feminization of parts of the antennal lobe and mushroom body by targeted expression
of a female-determining gene transformer
+ (tra
+) drives the male to court other males. Mutations in the tra target gene fruitless (fru), which is expressed in the antennal lobe as well as the suboesophageal ganglion (the gustatory inputs are processed here),
also induce homosexual courtship in males. These results suggest that sensory inputs mediated and/or processed by the tarsal
receptors, suboesophageal ganglion, antennal lobe and mushroom body contribute to the regulation of male–female courtship.
Mosaic analysis localized the neural center for male courtship behavior to the posterior dorsal brain, in which the sensory
information processed by the aforementioned neural structures may be integrated. Another mosaic study mapped the neural center
for female sexual behavior, as measured by her receptiveness to copulation, to the anterior dorsal brain. The issue as to
how the mutations that reduce female sexual receptiveness, e.g. dissatisfaction (dsf), spinster (spin) and chaste (cht), affect the structure and/or function of this neural center deserves to be addressed urgently.
Received 27 April 1999; received after revision 21 June 1999; accepted 8 July 1999 相似文献
10.
Protein kinase-dependent overexpression of the nuclear protein pirin in c-JUN and RAS transformed fibroblasts 总被引:1,自引:0,他引:1
Bergman AC Alaiya AA Wendler W Binetruy B Shoshan M Sakaguchi K Bergman T Kronenwett U Auer G Appella E Jörnvall H Linder S 《Cellular and molecular life sciences : CMLS》1999,55(3):467-471
Signalling via the protein kinase Raf-MEK-ERK pathway is of major importance for transformation by oncogenes. To identify
genes affected by inhibition of this pathway, c-JUN transformed rat fibroblasts were treated with a MEK1 inhibitor (PD98059) and subjected to two-dimensional gel electrophoresis
after cell lysis. Gene products with expression influenced by MEK1 inhibition were determined by mass spectrometry of fragments
from in-gel tryptic digestions. The expression of pirin, a nuclear factor I-interacting protein, was lowered after inhibition
of MEK1. Western blot analysis revealed increased expression of pirin in RAS and c-JUN transformed cells in the absence of PD98059. Inhibition of MEK1 also led to reduced expression of α-enolase, phosphoglycerate kinase, elongation factor 2 and heterogeneous nuclear ribonucleoprotein A3, the latter two being
detected as truncated proteins. In contrast, the level of ornithine aminotransferase was increased. We conclude that inhibition
of MEK1 results in major alterations of protein expression in c-JUN transformed cells, suggesting that this pathway is important for oncogene-induced phenotypic changes.
Received 30 December 1998; accepted 12 January 1999 相似文献
11.
Noncollagenous, nonproteoglycan macromolecules of cartilage 总被引:4,自引:0,他引:4
Extracellular matrix comprises approximately 90% of cartilage, with collagens and proteoglycans making up the bulk of the
tissue. In recent years, several abundant cartilage proteins that are neither collagens nor proteoglycans have been characterized
in detail. The putative roles of these proteins range from involvement in matrix organization or matrix-cell signaling (PRELP,
chondroadherin, cartilage oligomeric protein and cartilage matrix protein) through to molecules that are likely to be involved
with modulation of the chondrocyte phenotype (CD-RAP, CDMPs, chondromodulin and pleiotrophin). Other molecules, such as the
cartilage-derived C-type lectin and cartilage intermediate layer protein have no role as yet. Due to the difficulties associated
with experimentally manipulating a tissue that is 90% extracellular matrix in a manner that can be readily transferred to
the whole organism, many of these molecules have been focused on by a surprisingly small number of researchers. This review
focuses on newly discovered proteins and glycoproteins in cartilage, with a bias towards those that have structural roles
or that are unique to cartilage.
Received 7 January 1999; accepted 11 March 1999 相似文献
12.
C. Verderio S. Coco E. Pravettoni A. Bacci M. Matteoli 《Cellular and molecular life sciences : CMLS》1999,55(11):1448-1462
Hippocampal cultures offer unique advantages for the study of neuronal development and synaptogenesis. Studies performed
on this model enabled dissection of the temporal sequence of events which lead to the differentiation of pre- and postsynaptic
compartments.
Received 27 January 1999; received after revision 4 March 1999; accepted 5 March 1999 相似文献
13.
Ca2+ signaling plays a crucial role in virtually all cellular processes, from the origin of new life at fertilization to the end
of life when cells die. Both the influx of external Ca2+ through Ca2+-permeable channels and its release from intracellular stores are essential to the signaling function. Intracellular Ca2+ is influenced by mitogenic factors which control the entry and progression of the cell cycle; this is a strong indication
for a role of Ca2+ in the control of the cycle, but surprisingly, the possibility of such a role has only been paid scant attention in the literature.
Substantial progress has nevertheless been made in recent years in relating Ca2+ and the principal decoder of its information, calmodulin, to the modulation of various cycle steps. The aim of this review
is to critically discuss the evidence for a role of Ca2+ in the cell cycle and to discuss Ca2+-dependent pathways regulating cell growth and differentiation.
Received 2 March 2005; received after revision 9 May 2005; accepted 24 May 2005 相似文献
14.
Integrin antagonists 总被引:4,自引:0,他引:4
Integrins are a family of cell surface glycoproteins that mediate numerous cell-cell and cell-matrix interactions and are
involved in biological processes such as tissue morphogenesis, leukocyte recirculation and migration, wound healing, blood
clotting and immune response. Aberrant cell adhesion has been implicated in the pathogenesis of several diseases, including
a number of inflammatory disorders such as rheumatoid arthritis, inflammatory bowel disease and asthma, as well as cancer
and coronary heart disease. As such integrins are seen as excellent targets for the development of therapeutic agents. This
report begins with an examination of the structure of integrin molecules and their ligands and then goes on to review the
current state of development of antiintegrin antagonists.
Received 13 April 1999; received after revision 28 May 1999; accepted 28 May 1999 相似文献
15.
Low molecular weight protein tyrosine phosphatases (LMW-PTPs) are a family of 18-kDa enzymes involved in cell growth regulation.
Despite very limited sequence similarity to the PTP superfamily, they display a conserved signature motif in the catalytic
site. LMW-PTP associates and dephosphorylate many growth factor receptors, such as platelet-derived growth factor receptor
(PDGF-r), insulin receptor and ephrin receptor, thus downregulating many of the tyrosine kinase receptor functions that lead
to cell division. In particular, LMW-PTP acts on both growth-factor-induced mitosis, through dephosphorylation of activated
PDGF-r, and on cytoskeleton rearrangement, through dephosphorylation of p190RhoGAP and the consequent regulation of the small
GTPase Rho. LMW-PTP activity is modulated by tyrosine phosphorylation on two specific residues, each of them with specific
characteristics. LMW-PTP activity on specific substrates depends also on its localization. Moreover, LMW-PTP is reversibly
oxidized during growth factor signaling, leading to inhibition of its enzymatic activity. Recovery of phosphatase activity
depends on the availability of reduced glutathione and involves the formation of an S–S bridge between the two catalytic site
cysteines. Furthermore, studies on the redox state of LMW-PTP in contact-inhibited cells and in mature myoblasts suggest that
LMW-PTP is a general and versatile modulator of growth inhibition.
Received 17 January 2002; received after revision 22 March 2002; accepted 26 March 2002 相似文献
16.
The molecular recognition hypothesis for peptides is that binding sites of ligands and their receptors are encoded by short,
complementary segments of DNA. A corollary hypothesis for nonpeptide ligands posited here is that peptide replicas may be
encoded by the DNA segment complementary to the receptor binding sites for nonpeptides. This corollary was tested for digitalis,
a family of cardiotonic and natriuretic steroids including ouabain. A hexapeptide (ouabain-like peptide, OLP) complementary
to a ouabain binding site on sodium/potassium dependent adenosine triphosphatase (Na+ K+ ATPase) exhibited activity in a digitalis bioassay. Antisera to the complementary peptide (OLP) stained the neurohypophysis
in an immunocytochemical procedure. The complementary peptide was found to share an identical 4-amino acid region with the
39-amino acid glycopeptide moiety of the vasopressin-neurophysin precursor. This glycopeptide was isolated from pituitary
extracts; it exhibited digitalis-like activity in the submicromolar range and cross-reacted with complementary peptide antibodies.
Another digitalis-like substance with high activity also was detected in the extracts. These results demonstrate that the
vasopressin-neurophysin glycopeptide has digitalis-like activity. Moreover, the findings are consistent with the hypothesis
that peptide mimetics of nonpeptides are encoded in the genome.
Received 23 November 1998; received after revision 18 January 1999; accepted 19 February 1999 相似文献
17.
Myocardial infarction might result from the interactions of multiple genetic and environmental factors, none of which can cause disease solely by each of themselves. Although molecular biological studies revealed that a number of proteins are possibly involved in its pathogenesis, little, if any genetic findings have been reported so far. To reveal genetic backgrounds of myocardial infarction, we performed a large-scale, case-control association study using 92,788 gene-based single-nucleotide polymorphism (SNP) markers. We have identified functional SNPs within the lymphotoxin-α gene (LTA) located on chromosome 6p21 that conferred susceptibility to myocardial infarction. Furthermore, we could identify galectin-2 protein as a binding partner of LTA protein. The association study further revealed that a functional SNP in LGALS2 encoding galectin-2, which led to altered secretion of LTA, also indicated a risk of myocardial infarction. A combined strategy of genetic and molecularcellular biological approaches may be useful in clarifying pathogenesis of common diseases.Received 7 March 2005; received after revision 22 April 2005; accepted 25 April 2005 相似文献
18.
Comparison of the growing number of disorders known to be associated with triplet repeat expansions reveals both common features
and a diversity of molecular pathways. Despite significant progress towards the characterization of proteins coded by the
mutant genes, the complex nature of these disorders requires identification of all molecular components of the triplet repeat
pathways. In this brief review we will discuss recent progress in determining the molecular mechanisms of disorders with unstable
trinucleotide mutations.
Received 13 January 1999; received after revision 8 March 1999; accepted 9 March 1999 相似文献
19.
M. Pucéat 《Cellular and molecular life sciences : CMLS》1999,55(10):1216-1229
Intracellular pH (pHi) is a major regulator of various and critical cellular functions. A close regulation of pHi is thus mandatory to maintain normal cellular activity. To this end, all cells express ion transporters that carry across
their plasma membrane H+ or equivalent H+ into and out of the cell. Besides pHi, these ion transporters are under the regulation of neurohormonal stimuli. This review summarises the molecular identity,
regulation and function of the main membrane pH-regulatory ion transporters.
Received 30 December 1998; received after revision 4 February 1999; accepted 9 February 1999 相似文献
20.
Porcelli AM Ghelli A Mastrocola T Rugolo M 《Cellular and molecular life sciences : CMLS》1999,56(1-2):167-173
The Ca2+ ionophore ionomycin induced cytosolic [Ca2+]i elevation as well as strong activation of Cl− efflux in mouse mammary epithelial cell lines expressing wild-type or mutated (deletion of phenylalaline 508) cystic fibrosis
transmembrane conductance regulator (CFTR) or vector. Ionomycin-induced Cl− efflux was abolished by the intracellular Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid, whereas both activators and inhibitors of phospholipase A2 had no effect, indicating the involvement of Ca2+-dependent Cl- channels. Stimulation of arachidonic acid release by ionomycin and phorbol ester was not significantly different between
wild-type or mutated cell lines, whereas vector-transfected cells exhibited a significant higher release, which was shown
to be due to larger amount of immunoreactive cytosolic phospholipase A2. These results indicate that phospholipase A2 activity of C127 cells was not influenced by the presence of wild-type or mutated CFTR.
Received 27 April 1999; received after revision 11 June 1999; accepted 23 July 1999 相似文献