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1.
M. L. Rose 《Cellular and molecular life sciences : CMLS》1998,54(9):965-978
The immunological properties of human endothelial cells suggest they perform a pivotal role in acute and chronic rejection
following solid organ transplantation. In this review the basic features of acute and chronic rejection are described as are
the cellular and molecular requirements for antigen presentation. Traditionally, antigen-presenting cells are considered to
be bone marrow-derived cells. However, these conclusions have been derived from rodent models of allograft rejection where
bone marrow-derived passenger leukocytes are the only source of donor major histocompatibility complex (MHC) class II in the
grafted organ. In contrast, in humans, virtually all the microvascular and small vessel endothelial cells are ‘constitutively’
positive for MHC class II antigens. The phenotypic properties of human endothelial cells, their response to cytokines and
their ability to stimulate resting T cells are described. Unlike bone marrow-derived antigen presenting cells (APCs), which
utilise B7/CD28 interactions, human endothelial cells utilise lymphocyte function antigen 3 (LFA3)/CD2 pathways to stimulate
T cells. They activate a CD45RO + B7-independent subpopulation of T cells. Their effect on allogeneic T cells is compared
with other non-bone marrow-derived cells such as fibroblasts, epithelial cells and smooth muscle cells, which are unable to
stimulate resting T cells. Evidence is presented suggesting that release of MHC and non-human leukocyte antigens (HLA) from
endothelial cells stimulates an alloantibody and autoimmune response leading to chronic rejection.
Received 30 March 1998; received after revision 4 May 1998; accepted 4 May 1998 相似文献
2.
The V(D)J recombination activating protein RAG2 consists of a six-bladed propeller and a PHD fingerlike domain, as revealed by sequence analysis 总被引:3,自引:0,他引:3
The RAG1 and RAG2 proteins play a crucial role in V(D)J recombination by cooperating to make specific double-stranded DNA
breaks at a pair of recombination signal sequences (RSSs). However, the exact function they perform has heretofore remained
elusive. Using a combination of sensitive methods of sequence analysis, we show here that the active core region of the RAG2
protein, confined to the first three quarters of its sequence, is in fact composed of a six-fold repeat of a 50-residue motif
which is related to the kelch/mipp motif. This motif, which forms a four-stranded twisted antiparallel β sheet, is arranged in a circular formation like blades of a propeller or turbine. Given the known properties of the β-propeller fold in mediating protein-protein interactions, it is proposed that this six-laded propeller structure of the RAG2
active core would play a crucial role in the tight complex formed by the RAG1 and RAG2 proteins and RSSs. Moreover, the presence
of a plant homeodomain finger-like motif in the last quarter of the RAG2 sequence suggests a potential interaction of this
domain with chromatin components.
Received 6 June 1998; accepted 9 June 1998 相似文献
3.
Protein kinases: which one is the memory molecule? 总被引:12,自引:0,他引:12
Encoding of new experiences is likely to induce activity-dependent modifications in the brain. Studies in organisms far apart
on the phylogenetic scale have shown that similar, sometimes identical, signal transduction pathways subserve plasticity in
neuronal systems, and they may play pivotal roles in the formation of long-term memories. It has become evident that phosphorylation/dephosphorylation
reactions are critical for the initiation of cellular mechanisms that embody, retain and modify information in neural circuits.
Although physiological investigations on synaptic plasticity have had a major impact, we have concentrated our review on behavioural
studies that provide direct or indirect evidence for a role of kinases in mechanisms underlying memory formation. From these,
it appears that the learning event induces activation of a variety of kinases with specific time courses. For instance, the
calcium/calmodulin-dependent protein kinase II seems to participate in an early phase of memory formation. Apparently, activation
of both protein tyrosine kinases and mitogen-activated protein kinases is required for much longer and may thus have a particular
function during transformation from short-term into long-term memory. Quite different time courses appear for protein kinase
C (PKC) and protein kinase A (PKA), which may function at two different time points, shortly after training and again much
later. This suggests that PKC and PKA might play a role at early and late stages of memory formation. However, we have considered
some examples showing that these signalling pathways do not function in isolation but rather interact in an intricate intracellular
network. This is indicative of a more complex contribution of each kinase to the fine tuning of encoding and information processing.
To decipher this complexity, pharmacological, biochemical and genetic investigations are more than ever necessary to unravel
the role of each kinase in the syntax of learning and memory formation. 相似文献
4.
Silberman DM Zorrilla-Zubilete M Cremaschi GA Genaro AM 《Cellular and molecular life sciences : CMLS》2005,62(15):1744-1754
Chronic stress has been associated with impaired immune function. In this work we studied the effect of chronic mild stress (CMS) exposure on the early intracellular pathways involved in T cells after stimulation with mitogen. We found that mitogen stimulation of T lymphocytes from CMS-exposed mice resulted in a reduction of the intracellular [Ca2+] rise, an impairment of growth-promoting protein kinase C (PKC) activation, a lower NF-κB activation and an increase in the inhibitory cAMP-protein kinase A (PKA) pathway activity with respect to those found in control lymphocytes. However, T cell activation with the direct PKC activator phorbol 12-myristate 13-acetate plus calcium ionophore led to a similar proliferative response in both CMS and control lymphocytes, indicating that signals downstream of PKC would not be affected by stress. In summary, our results show that chronic stress induced an alteration in T cell early transduction signals that result in an impairment of the proliferative response.Received 11 February 2005; received after revision 20 May 2005; accepted 6 June 2005 相似文献
5.
Myelin sheaths: glycoproteins involved in their formation,maintenance and degeneration 总被引:8,自引:0,他引:8
Quarles RH 《Cellular and molecular life sciences : CMLS》2002,59(11):1851-1871
Myelin sheaths are formed around axons by extending, biochemically modifying and spiraling plasma membranes of Schwann cells
in the peripheral nervous system (PNS) and oligodendrocytes in the central nervous system (CNS). Because glycoproteins are
prominent components of plasma membranes, it is not surprising that they have important roles in the formation, maintenance
and degeneration of myelin sheaths. The emphasis in this review is on four integral membrane glycoproteins. Two of them, protein
zero (P0) and peripheral myelin protein-22 (PMP-22), are components of compact PNS myelin. The other two are preferentially
localized in membranes of sheaths that are distinct from compact myelin. One is the myelin-associated glycoprotein, which
is localized at the inside of sheaths where it functions in glia-axon interactions in both the PNS and CNS. The other is the
myelin-oligodendrocyte glycoprotein, which is preferentially localized on the outside of CNS myelin sheaths and appears to
be an important target antigen in autoimmune demyelinating diseases such as multiple sclerosis.
Received 8 April 2002; received after revision 13 May 2002; accepted 22 May 2002 相似文献
6.
H. Van Dael 《Cellular and molecular life sciences : CMLS》1998,54(11):1217-1230
Protein folding is an extremely active field of research where biology, chemistry, computer science and physics meet. Although
the study of protein-folding intermediates in general and equilibrium intermediates in particular has grown considerably in
recent years, many questions regarding the conformational state and the structural features of the various partially folded
intermediate states remain unanswered. Performing kinetic measurements on proteins that have had their structures modified
by site-directed mutagenesis, the so-called protein-engineering method, is an obvious way to gain fine structural information.
In the present review, this method has been applied to a variety of proteins belonging to the lysozyme/α-lactalbumin family. Besides recombinants obtained by point mutations of individual critical residues, chimeric proteins in
which whole structural elements (10 – 25 residues) from α-lactalbumin were inserted into a human lysozyme matrix are examined. The conformational properties of the equilibrium intermediate
states are discussed together with the structural characterization of the partially unfolded states encountered in the kinetic
folding pathway.
Received 28 May 1998; received after revision 6 July 1998; accepted 6 July 1998 相似文献
7.
8.
V. J. Csernus T. Hammer D. Peschke E. Peschke 《Cellular and molecular life sciences : CMLS》1998,54(7):733-743
Insulin secretion from isolated pancreatic islets of 8- to 12-day-old rats was investigated in a dynamic in vitro (perifusion)
system. The aims of the study were (i) to describe a carefully controlled in vitro method to study the mechanism of insulin
secretion and to analyse the effects and dynamic interactions of bioactive compounds on isolated rat pancreatic islets, (ii)
to validate the method by comparing fundamental data on the functions of the islets obtained with this method to those collected
with other techniques; and (iii) to find novel features of the control of insulin secretion. The method was carefully designed
to maintain the functional capacity of the explanted cells. A functional standardization system was elaborated consisting
of (i) analysis of the changes in the basal hormone secretion of the cells; (ii) evaluating responses to a standard, specific
stimuli (50 mM glucose for 3 min); (iii) determining the alteration of the momentary size of the hormone pool with responses
to KCl; and (iv) direct determination of the total intracellular hormone content from the extract of the column. The technique
provides accurate quantitative data on the dynamic responses to biologically active compounds that act directly on the pancreatic
islets. The islets maintained their full responsiveness for up to 7 days, and responses as close as in 1-min intervals could
be distinguished. A linear dose-response relationship was found on the glucose-induced insulin release in case of 3-min stimulation
with 4 and 500 mM of glucose (lin-log graph). Utilizing this method, we showed that no desensitization to glucose-induced
insulin release can be observed if the responsiveness of the cells is properly maintained and the parameters of the stimulation
are carefully designed. Exposure of the explanted islets to 10 μM acetylcholine or 30 mM arginine (Arg) induced a transitory
elevation of insulin release similar in shape to that experienced after glucose stimulation. Norepinephrine (NE), dopamine
(DA) and somatostatin (SS) did not induce any detectable alteration on the basal insulin secretion of the islets. However,
100 nM SS given together with 50 mM glucose, 30 mM Arg or 10 μM acetylcholine significantly reduced the insulin-releasing
effect of these substances (by 75.5, 71.5 and 72.5%, respectively). At the same time, SS did not alter the insulin response
of the islets to 100 mM elevation of K+ concentration. SS also inhibited glucose-induced insulin release in a dose-dependent way (ED50 = 22 nM). A similar dose-dependent inhibitory effect on glucose-induced insulin release was found with NE (ED50 = 89 nM) and DA (ED50 = 2.2 μM). γ-Aminobutyric acid (GABA) did not influence insulin release under similar circumstances.
Received 16 January 1998; received after revision 6 May 1998; accepted 8 May 1998 相似文献
9.
Ciruela F Ferré S Casadó V Cortés A Cunha RA Lluis C Franco R 《Cellular and molecular life sciences : CMLS》2006,63(21):2427-2431
Since 1990 it has been known that dimers are the basic functional form of nearly all G-protein-coupled receptors (GPCRs) and
that homo- and heterodimerization may play a key role in correct receptor maturation and trafficking to the plasma membrane.
Nevertheless, homo- and heterodimerization of GPCR has become a matter of debate especially in the search for the precise
physiological meaning of this phenomenon. This article focuses on how heterodimerization of adenosine A1 and A2A receptors, which are coupled to apparently opposite signalling pathways, allows adenosine to exert a fine-tuning modulation
of striatal glutamatergic neurotransmission, providing a switch mechanism by which low and high concentrations of adenosine
inhibit and stimulate, respectively, glutamate release.
Received 8 May 2006; received after revision 19 June 2006; accepted 17 July 2006 相似文献
10.
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
11.
Glutamic acid decarboxylase (GAD) is considered to be one of the strongest candidate autoantigens involved in triggering
β-cell-specific autoimmunity. The majority of recent onset type 1 diabetes patients and prediabetic subjects have anti-GAD
antibodies in their sera, as do nonobese diabetic (NOD) mice, one of the best animal models for human type 1 diabetes. Immunization
of young NOD mice with GAD results in the prevention or delay of the disease as a result of tolerizing autoreactive T cells.
Autoimmune diabetes can also be prevented by the suppression of GAD expression in antisense GAD trans genic mice backcrossed
with NOD mice for seven generations. These results support the hypothesis that GAD plays an important role in the development
of T-cell-mediated autoimmune diabetes. However, there is some controversy regarding the role of GAD in the pathogenesis of
diabetes. Whether GAD truly plays a key role in the initiation of this disease remains to be determined. The examination of
the development of insulitis and diabetes in β-cell-specific GAD knockout NOD mice will answer this remaining question.
Received 12 April 2002; received after revision 24 May 2002; accepted 27 May 2002
RID="*"
ID="*"Corresponding author. 相似文献
12.
M. Fontecave 《Cellular and molecular life sciences : CMLS》1998,54(7):684-695
Ribonucleotide reductases (RNRs) catalyse the reduction of ribonucleotides to deoxyribonucleotides. They play a pivotal role
in the regulation of DNA synthesis and are targets for antiproliferative drugs. Ribonucleotide reductases are unique enzymes
in that they all require a protein radical for activity. Class I nonheme iron RNRs (mammals, plants, Escherichia coli) use a tyrosyl/cysteinyl radical pair, class II adenosylcobalamin RNRs (prokaryotes, archaea) a cysteinyl radical, class
III iron-sulphur RNRs (facultative anaerobes) a glycyl radical. Here we describe the reactivity of these radicals with respect
to the natural ribonucleotide substrates as well as to a variety of enzyme inhibitors, radical scavengers, nitric oxide, superoxide
radicals and substrate analogues.
Received 3 December 1997; received after revision 26 February 1998; accepted 27 February 1998 相似文献
13.
Scavenger receptor family proteins: roles for atherosclerosis, host defence and disorders of the central nervous system 总被引:11,自引:1,他引:10
Y. Yamada T. Doi T. Hamakubo T. Kodama 《Cellular and molecular life sciences : CMLS》1998,54(7):628-640
In this review, we summarize the structure and function of the scavenger receptor family of proteins including class A (type
I and II macrophage scavenger receptors, MARCO), class B (CD36, scavenger receptor class BI), mucinlike (CD68/macrosialin,
dSR-CI) and endothelial (LOX-1) receptors. Two motifs have been identified as ligand-binding domains a charged collagen structure
of type I and II receptors, and an immunodominant domain of CD36. These structures can recognize a wide range of negatively
charged macromolecules, including oxidized low-density lipoproteins, damaged or apoptotic cells, and pathogenic microorganisms.
After binding, these ligands can be either internalized by endocytosis or phagocytosis, or remain at the cell surface and
mediate adhesion or lipid transfer through caveolae. Under physiological conditions, scavenger receptors serve to scavenge
or clean up cellular debris and other related materials, and they play a role in host defence. In pathological states, they
mediate the recruitment, activation and transformation of macrophages and other cells which may be related to the development
of atherosclerosis and to disorders caused by the accumulation of denatured materials, such as Alzheimer's disease.
Received 17 September 1997; received after revision 16 March 1998; accepted 17 March 1998 相似文献
14.
Epithelial supporting cells can differentiate into outer hair cells and Deiters' cells in the cultured organ of Corti 总被引:2,自引:0,他引:2
Malgrange B Thiry M Van De Water TR Nguyen L Moonen G Lefebvre PP 《Cellular and molecular life sciences : CMLS》2002,59(10):1744-1757
The organ of Corti is a complex structure containing a single row of inner hair cells (IHCs) and three rows of outer hair
cells (OHCs), supported respectively by one row of inner phalangeal cells and three rows of Deiters' cells. When fetal rat
organ of Corti explants are cultured, supernumerary OHCs and supernumerary Deiters' cells are produced, without any additional
cell proliferation. Analysis of semi- and ultrathin sections revealed that supernumerary OHCs are produced at the distal edge
of the organ of Corti. Quantitative analysis of cell types present in the organ of Corti demonstrates that when the number
of OHCs increases: (i) the total number of cells remains constant; (ii) the number of Deiters' cells increases; (iii) the
number of tectal cells decreases and of Hensen's cells decreases. Using specific HC markers, i.e. jagged2 (Jag2) and Math1,
we showed that in addition to existing OHCs, supernumerary OHCs, tectal cells and Hensen's cells expressed these markers in
embryonic day 19 organ of Corti explants after 5 days in vitro. The results of this study suggest that Hensen's cells retain
the capacity to differentiate into either tectal cells, which differentiate into OHCs, or into undertectal cells which differentiate
into Deiters' cells.
Received 15 May 2002; received after revision 18 July 2002; accepted 7 August 2002
RID="*"
ID="*"Corresponding author. 相似文献
15.
Immunological evidence suggests that plants, like vertebrates, contain natriuretic peptides (NPs) and that rat atrial NP
(rANP) binds specifically to plant membranes and promotes concentration and conformation-dependent stomatal opening. Stomatal
opening and specific increases in cGMP levels were also observed in response to immunoreactive plant NP (irPNP). Here we report
that both 1 μM rANP and irPNP (100 ng total protein/100 μL) significantly increase radial water movements out of the xylem
of shoots of Tradescantia multiflora. Enhanced radial water movements are also observed in response to the cell permeant cGMP analogue 8-Br-cGMP (100 nM). The
water channel inhibitor mercuric chloride (HgCl2) significantly inhibits radial water movements at concentrations of 50 μM, while the presence of 10 μM 2-hydroxyethylmercaptoethanol
(ME) prevents the inhibitory effect of the mercurial. The guanylate cyclase inhibitor LY 83583 at a concentration of 20 μM
and sodium azide (NaN3) at concentrations of ≥ 1 μM both also reduce radial water movements. We therefore conclude that the regulation of radial
water movement out of the xylem involves modulation of cGMP levels, water channels and respiration-dependent processes. In
addition, we propose that NPs have a critical role to play in radial water movements out of the xylem and speculate that as
in vertebrates, NP effects might, at least in part, be mediated via the regulation of guanylate cyclases and water channels.
Received 15 June 1998; received after revision 7 August 1998; accepted 26 August 1998 相似文献
16.
Protein tyrosine phosphatases (PTPs) have emerged as a new class of signaling molecules that play important roles in the development and function of the central nervous system. They include both tyrosine-specific and dual-specific phosphatases. Based on their cellular localization they are also classified as receptor-like or intracellular PTP. However, the intracellular mechanisms by which these PTPs regulate cellular signaling pathways are not well understood. Evidence gathered to date provides some insight into the physiological function of these PTPs in the nervous system. In this review, we outline what is currently known about the functional role of PTPs expressed in the brain.Received 31 March 2003; received after revision 7 May 2003; accepted 22 May 2003 相似文献
17.
C. Elsing J. Górski C. Boeker W. Stremmel 《Cellular and molecular life sciences : CMLS》1998,54(7):744-750
Studies of regulation of free fatty acid (FFA) utilization by skeletal muscles have focused on plasma FFA delivery and on
intracellular factors affecting FFA metabolism. The present study was conducted to directly analyse the uptake process of
fatty acids into single myocytes. Cells were isolated from the rat flexor digitorum brevis muscle. Confocal laser scanning
microscopy was utilized to analyse the uptake of the fluorescent fatty acid derivative 12-NBD-stearate, which is not metabolized
by muscle tissue. Uptake represented a saturable function of the unbound fatty acid concentration in the medium (K
m 366 ± 118 nM, V
max 2.1 ± 0.3 AU/s) and depended on the medium sodium concentration. Reduced buffer pH increased initial uptake rates, whereas
lactate (10 mM) had no effect. Membrane hyper- and depolarization decreased uptake rates. This study demonstrates for the
first time kinetic data from isolated myocytes with evidence for a carrier-mediated transport mechanism for long-chain fatty
acids.
Received 31 March 1998; accepted 8 May 1998 相似文献
18.
19.
Central nervous system stem cells in the embryo and adult 总被引:19,自引:0,他引:19
J. Frisén C. B. Johansson C. Lothian U. Lendahl 《Cellular and molecular life sciences : CMLS》1998,54(9):935-945
The central nervous system is generated from neural stem cells during embryonic development. These cells are multipotent
and generate neurons, astrocytes and oligodendrocytes. The last few years it has been found that there are populations of
stem cells also in the adult mammalian brain and spinal cord. In this paper, we review the recent development in the field
of embryonic and adult neural stem cells.
Received 26 March 1998; received after revision 27 April 1998; accepted 27 April 1998 相似文献
20.
M. P. Mollica S. Iossa G. Liverini S. Soboll 《Cellular and molecular life sciences : CMLS》1998,54(11):1277-1282
Changes in mitochondrial function were studied in perfused liver from rats aged 24 – 365 days. Oxygen consumption together
with the rates of gluconeogenesis, urea synthesis and ketogenesis were determined. Basal mitochondrial respiration as well
as the ability of the liver to synthesize glucose, urea and ketone bodies declined from 24- to 365-day-old rats. On the other
hand, on transition from 24 to 60 days the liver oxidation rate of hexanoate, sorbitol and glycerol is enhanced, but not of
ketone bodies or palmitate. Our results show that the transition from weaning to middle age is accompanied by defined changes
in hepatic substrate oxidation. From the observed time course of the decrease in basal and substrate-stimulated oxygen consumption,
it is concluded that in rat liver cells a decline in respiratory chain function, long-chain fatty acid and ketone body metabolism,
gluconeogenesis and ureogenesis occurs at a relatively early life stage.
Received 19 June 1998; received after revision 11 September 1998; accepted 11 September 1998 相似文献