共查询到20条相似文献,搜索用时 656 毫秒
1.
Pani A Batetta B Putzolu M Sanna F Spano O Piras S Mulas MF Bonatesta RR Amat di S Filippo C Vargiu L Marceddu T Sanna L La Colla P Dessì S 《Cellular and molecular life sciences : CMLS》2000,57(7):1094-1102
The product of the MDR1 gene (P-gp) has been implicated in the transport of cholesterol from plasma membrane to endoplasmic reticulum for esterification.
In previous studies on leukemia cell lines, we suggested that cholesterol esterification may regulate the rate of cell growth
and that the MDR1 gene might be involved in this process by modulating intracellular cholesterol esters levels. To further investigate this
matter, the rate of cell growth, cholesterol metabolism, expression of the MDR1 gene, and P-gp activity were compared in KB cell lines displaying differences in expression and function of P-gp (drug-sensitive
phenotype versus MDR phenotype). The rate of cell growth correlated with cholesterol esterification in all KB cell lines,
whereas the over-expression of MDR1 observed in the MDR cell lines was not always associated with an increased capacity of cells to esterify cholesterol. Two
known inhibitors of P-gp activity, progesterone and verapamil, strongly inhibited both cholesterol esterification and cell
proliferation in all KB cell lines, but they affected intracellular accumulation of labeled vinblastine only in MDR cell lines.
These results further support a role for cholesterol esters in the regulation of cell growth and suggest that the P-gp expressed
in MDR KB cells is not involved in the general process leading to cholesterol esterification.
Received 14 February 2000; received after revision 10 April 2000; accepted 8 May 2000 相似文献
2.
Y. Liang T. L. Jetton M. Lubkin A. H. Meier A. H. Cincotta 《Cellular and molecular life sciences : CMLS》1998,54(7):703-711
Dysfunction of pancreatic islets plays a crucial role in the etiology of type II diabetes. Chronic hyperglycaemia or hyperlipidaemia
may impair islet function. Previous studies by our laboratory have demonstrated that dopaminergic agonists ameliorated hyperglycaemia
and hyperlipidaemia in obese and diabetic rodents. In the present study, we investigated the effect of a treatment with the
dopamine D2 /D1 receptor agonists (bromocriptine/SKF38393, BC/SKF) on islet dysfunction in db/db mice. Our results show that a 2-week BC/SKF treatment markedly reduced hyperglycaemia and hyperlipidaemia, and significantly
improved islet dysfunction demonstrated by an increase of secretagogue-stimulated insulin release from islets of db/db mice to levels observed in islets from lean mice. There was also a fourfold increase of insulin content in the pancreas of
BC/SKF-treated db/db mice compared with that in untreated controls. The effect of BC/SKF on islet function cannot be mimicked in pair-fed animals.
BC/SKF had no direct stimulatory effect on islet insulin secretion, suggesting BC/SKF treatment improved islet function via
an indirect mechanism. This treatment markedly improved the abnormally elevated daily levels of corticosterone, blood glucose
and plasma lipids, supporting the view that BC/SKF may affect the neuroendocrine system that in turn regulates peripheral
metabolism and thereby improves islet function.
Received 3 April 1998; accepted 27 April 1998 相似文献
3.
One of the central elements of excitation-contraction coupling, the voltage-sensing dihydropyridine receptor, is believed
to exist as a high-molecular-mass complex in the triad junction. Although freeze-fracture electron microscopical analysis
suggests a tetrad complex, no direct biochemical evidence exists demonstrating the actual size of the native membrane complex.
Using a combination of various two-dimensional gel electrophoresis techniques, we show here that the principal α
1-subunit of the dihydropyridine receptor and its auxiliary α
2-subunit form a triad complex of approximately 2800 kDa under native conditions. Established Ca2+-ATPase tetramers and calsequestrin monomers were employed for the internal standardization of the gel systems used. Thus,
the large voltage-sensing complex appears to be tightly associated, since it does not disintegrate during subcellular fractionation
and native electrophoresis procedures. Our findings support the cell biological hypothesis that native dihydropyridine receptor
units form a tetrad structure within the transverse tubules.
Received 10 October 2000; revised 28 November 2000; accepted 4 January 2001 相似文献
4.
In this paper, we examine the use of non‐parametric Neural Network Regression (NNR) and Recurrent Neural Network (RNN) regression models for forecasting and trading currency volatility, with an application to the GBP/USD and USD/JPY exchange rates. Both the results of the NNR and RNN models are benchmarked against the simpler GARCH alternative and implied volatility. Two simple model combinations are also analysed. The intuitively appealing idea of developing a nonlinear nonparametric approach to forecast FX volatility, identify mispriced options and subsequently develop a trading strategy based upon this process is implemented for the first time on a comprehensive basis. Using daily data from December 1993 through April 1999, we develop alternative FX volatility forecasting models. These models are then tested out‐of‐sample over the period April 1999–May 2000, not only in terms of forecasting accuracy, but also in terms of trading efficiency: in order to do so, we apply a realistic volatility trading strategy using FX option straddles once mispriced options have been identified. Allowing for transaction costs, most trading strategies retained produce positive returns. RNN models appear as the best single modelling approach yet, somewhat surprisingly, model combination which has the best overall performance in terms of forecasting accuracy, fails to improve the RNN‐based volatility trading results. Another conclusion from our results is that, for the period and currencies considered, the currency option market was inefficient and/or the pricing formulae applied by market participants were inadequate. Copyright © 2002 John Wiley & Sons, Ltd. 相似文献
5.
4-Hydroxynonenal-modified amyloid-beta peptide inhibits the proteasome: possible importance in Alzheimer's disease 总被引:3,自引:0,他引:3
Shringarpure R Grune T Sitte N Davies KJ 《Cellular and molecular life sciences : CMLS》2000,57(12):1802-1809
The amyloid β-peptide (Aβ) is a 4-kDa species derived from the amyloid precursor protein, which accumulates in the brains of patients with Alzheimer’s
disease. Although we lack full understanding of the etiology and pathogenesis of selective neuron death, considerable data
do imply roles for both the toxic Aβ and increased oxidative stress. Another significant observation is the accumulation of abnormal, ubiquitin-conjugated proteins
in affected neurons, suggesting dysfunction of the proteasome proteolytic system in these cells. Recent reports have indicated
that Aβ can bind and inhibit the proteasome, the major cytoslic protease for degrading damaged and ubiquitin-conjugated proteins.
Earlier results from our laboratory showed that moderately oxidized proteins are preferentially recognized and degraded by
the proteasome; however, severely oxidized proteins cannot be easily degraded and, instead, inhibit the proteasome. We hypothesized
that oxidatively modified Aβ might have a stronger (or weaker) inhibitory effect on the proteasome than does native Aβ. We therefore also investigated the proteasome inhibitory action of Aβ
1–40 (a peptide comprising the first 40 residues of Aβ) modified by the intracellular oxidant hydrogen peroxide, and by the lipid peroxidation product 4-hydroxynonenal (HNE). H2O2 modification of Aβ
1–40 generates a progressively poorer inhibitor of the purified human 20S proteasome. In contrast, HNE modification of Aβ
1–40 generates a progressively more selective and efficient inhibitor of the degradation of fluorogenic peptides and oxidized
protein substrates by human 20S proteasome. This interaction may contribute to certain pathological manifestations of Alzheimer’s
disease
Received 26 September 2000; accepted 26 September 2000 相似文献
6.
Suzuki Y 《Cellular and molecular life sciences : CMLS》2008,65(3):351-353
We have proposed a chemical chaperone therapy for lysosomal diseases, based on a paradoxical phenomenon that an exogenous
competitive inhibitor of low molecular weight stabilizes the target mutant molecule and restores its catalytic activity as
a molecular chaperone intracellularly. After Fabry disease experiments, we investigated a new synthetic chaperone compound
N-octyl-4-epi-β-valienamine (NOEV) in a GM1-gangliosidosis model mice. Orally administered NOEV entered the brain through the blood-brain barrier, enhanced β-galactosidase
activity, reduced the substrate storage, and clinically improved neurological deterioration. We hope that chemical chaperone
therapy will prove useful for some patients with GM1-gangliosidosis and potentially other lysosomal storage diseases with central nervous system involvement.
Received 10 October 2007; received after revision 31 October 2007; accepted 6 November 2007 相似文献
7.
Adams V Lyras D Farrow KA Rood JI 《Cellular and molecular life sciences : CMLS》2002,59(12):2033-2043
Mobilisable transposons are transposable genetic elements that also encode mobilisation functions but are not in themselves
conjugative. They rely on coresident conjugative elements to facilitate their transfer to recipient cells. Clostridial mobilisable
transposons include Tn4451 and Tn4452 from Clostridium perfringens, and Tn4453a and Tn4453b from Clostridium difficile, all of which are closely related, and Tn5398 from C. difficile. The Tn4451 group of elements encodes resistance to chloramphenicol and is unusual in that transposition is dependent upon a large resolvase
protein rather than a more conventional transposase or integrase. This group of elements also encodes the mobilisation protein
TnpZ that, by acting at the RSA or oriT site located on the transposon, and in the presence of a coresident conjugative element, promotes the movement of the nonreplicating
circular intermediate and
of plasmids on which the transposon resides. The erythromycin resistance element Tn5398 is unique in that it encodes no readily identifiable transposition or mobilisation proteins. However, the element is still
capable of intraspecific transfer between C. difficile isolates, by an unknown mechanism. The detailed analysis of these mobilisable clostridial elements provides evidence that
the evolution and dissemination of antibiotic resistance genes is a complex process that may involve the interaction of genetic
elements with very different properties.
RID="*"
ID="*"Corresponding author. 相似文献
8.
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
9.
Kinetics of BRCA1 regulation in response to UVC radiation 总被引:1,自引:0,他引:1
To investigate changes in BRCA1 following DNA damage, we exposed MCF-7 cells to increasing doses of ultraviolet C. We observed
an increase in BRCA1 protein levels above 78 J/m2. This increase was observed as early as 5 min after irradiation. BRCA1 levels were then observed to decrease after 2 h, consistent
with the previously published data. By pretreating with cycloheximide prior to irradiation, we observed a decrease in the
protein half-life, from 3.5 h to 53 min, suggesting that a decrease in protein half-life may cause the lower levels of BRCA1
after irradiation. We also observed an increase in BRCA1 mRNA within 15 min of irradiation, followed by a decrease after 4
h. These data suggest that newly translated protein may contribute to increases in BRCA1 protein levels. The very rapid changes
in BRCA1 support its role as a sensor of DNA damage, as opposed to being a repair gene.
Received 6 April 2000; received after revision 23 May 2000; accepted 23 May 2000 相似文献
10.
Leukocyte integrins and inflammation 总被引:6,自引:0,他引:6
C. G. Gahmberg L. Valmu S. Fagerholm P. Kotovuori E. Ihanus L. Tian T. Pessa-Morikawa 《Cellular and molecular life sciences : CMLS》1998,54(6):549-555
Leukocyte adhesion is of pivotal functional importance. Without adequate adhesion, T lymphocytes and natural killer cells
are not cytotoxic, B cells cannot develop into antibody secreting plasma cells, leukocytes do not home into inflamed tissues
and myeloid cells are not able to phagocytize or exhibit chemotactic responses. During evolution several leukocyte adhesion
molecules have developed belonging to a few molecular families. Among these, the leukocyte-specific integrins (β
2 integrins, CD11/CD18 molecules) are among the most important. Much progress has taken place during the past few years, and
at present we have a considerable knowledge of their structure and function. Inflammation is critically dependent on integrin
activity, and its regulation forms the topic of this short review. 相似文献
11.
S. Sokoloff S. Halevy Varda Usieli A. Colorni S. Sarel 《Cellular and molecular life sciences : CMLS》1982,38(3):337-338
Summary The antibiotic properties of 2 acidic C24H40O4 nor-sesterterpenoid peroxides, prianicin A (1) and B (2), against gram-positive and gram-negative bacteria, and against fungi are herein described. They are 4–10 times more effective than tetracycline againstbeta hemolytic Streptococcus, but significantly non-effective against a variety of gram-negative bacteria.Acknowledgment. The authors are grateful to Prof. A. Kjaer of the Organic Chemistry Department of the Technical University of Denmark, for his help and fruitful discussions. 相似文献
12.
In this paper we show that optimal trading results can be achieved if we can forecast a key summary statistic of future prices. Consider the following optimization problem. Let the return ri (over time i=1, 2, ..., n) for the ith day be given and the investor has to make investment decision di on the ith day with di=1 representing a ‘long' position and di=0 a ‘neutral' position. The investment return is given by r=Σni=1ridi−cΣn+1i=1∣di−di−1∣, where c is the transaction cost. The mathematical programming problem of choosing d1, ..., dn to maximize r under a given transaction cost c is shown to have an analytic solution, which is a function of a key summary statistic called the largest change before reversal. The largest change before reversal is recommended to be used as an output in a neural network for the generation of trading signals. When neural network forecasting is applied to a dataset of Hang Seng Index Futures Contract traded in Hong Kong, it is shown that forecasting the largest change before reversal outperforms the k‐step‐ahead forecast in achieving higher trading profits. Copyright © 2000 John Wiley & Sons, Ltd. 相似文献
13.
Oka T Nishimoto Y Sasagawa T Kanouchi H Kawasaki Y Natori Y 《Cellular and molecular life sciences : CMLS》1999,55(1):131-134
An efficient Escherichia coli expression system for the production of a perchloric acid-soluble protein (PSP) has been constructed. Complementary DNA encoding
PSP was inserted into an inducible bacterial expression vector pGEX-4T-1. After the plasmid introduced into E. coli was expressed by isopropyl 1-thio-β-D-galactopyranoside (IPTG), the recombinant product was purified by glutathione-Sepharose 4B affinity chromatography. The
purified product showed the expected NH2-terminal sequence, but the translation inhibitory activity of this product was 10 times lower compared with that of authentic
PSP isolated from rat liver.
Received 8 October 1998; received after revision 6 November 1998; accepted 6 November 1998 相似文献
14.
F. Buzzetti F. Eisenberg H. N. Grant W. Keller-Schierlein W. Voser H. Zähner 《Cellular and molecular life sciences : CMLS》1968,24(4):320-323
Summary A strain ofStreptomyces viridochromogenes produced a new crystalline antibiotic, Avilamycin, related to but not identical with Curamycin and Exfoliatin. Avilamycin, C63H94O35Cl2, gave on solvolytic degradation the following products: dichloroisoeverninic acid, 2-deoxy-d-rhamnose, 2,6-di-O-methylmannose, 4-O-methylfucose,l-lyxose and 3,5-diacetoxy--caprolactone. 相似文献
15.
Summary Tunicamycin, an antibiotic, and diflubenzuron, an insect growth regulator, were tested to determine their effects on N-acetylglucosaminyl transferase fromS. calcitrans prepupae. Diflubenzuron had no effect, but tunicamycin inhibited the transfer of GlcNAc-1-P from UDP-GlcNAc to dolicholmonophosphate with an I50 of 1.5–4 ng/ml. 相似文献
16.
Sánchez-Margalet V González-Yanes C Santos-Alvarez J Najib S 《Cellular and molecular life sciences : CMLS》1999,55(1):142-147
Insulin action is initiated by binding to its cognate receptor, which then triggers multiple cellular responses by activating
different signaling pathways. There is evidence that insulin receptor signaling may involve G protein activation in different
target cells. We have studied the activation of G proteins in rat hepatoma (HTC) cells. We found that insulin stimulated binding
of guanosine 5′-O-(3-thiotriphosphate) (GTP-γ-35S) to plasma membrane proteins of HTC cells, in a dose-dependent manner. This effect was completely blocked by pertussis toxin
treatment of the membranes, suggesting the involvement of G proteins of the Gα
i/Gα
o family. The expression of these Gα proteins was checked by Western blotting. Next, we used blocking antibodies to sort out the specific Gα protein activated by insulin stimulation. Anti-Gα
il,2 antibodies completely prevented insulin-stimulated GTP binding, whereas anti-Gα
o,i3 did not modify this effect of insulin on GTP binding. Moreover, we found physical association of the insulin receptor with
Gα
i1,2 by copurification studies. These results further support the involvement of a pertussis toxin-sensitive G protein in insulin
receptor signaling and provides some evidence of specific association and activation of Gα
i1,2 protein by insulin. These findings suggest that Gα
i1,2 proteins might be involved in insulin action.
Received 23 September 1998; received after revision 23 November 1998; accepted 25 November 1998 相似文献
17.
A. Zhang T. P.-O. Cheng X. Y. Wu B. T. Altura B. M. Altura 《Cellular and molecular life sciences : CMLS》1997,53(1):69-72
Effects of extracellular magnesium ions ([Mg2+]o ) on intracellular free Mg2+ ([Mg2+]i ) and its subcellular distribution in single fission yeast cells, Schizosaccharomyces pombe, were studied with digital-imaging microscopy and an Mg2+ fluorescent probe (mag-fura-2). Using 0.44 mM [Mg2+]o , [Mg2+]i in yeast cells was 0.91±0.08 mM. Elevation of [Mg2+]o to 1.97 mM induced rapid (within 5 min) increments in [Mg2+]i (2.18±0.11 mM). Lowering [Mg2+]o to 0.06 mM, however, exerted no significant effects on [Mg2+]i (0.93±0.14 mM), at least for periods of up to 30 min. Irrespective of the [Mg2+]o used, the subcellular distribution of [Mg2+]i remained hetero
geneous, i.e. where the sub-plasma membrane region >cytoplasm >nucleus. [Mg2+] in all three subcellular compartments increased significantly, two- to threefold, concomitant with [Mg2+]i when placed in 1.97 mM [Mg2+]o . We conclude that [Mg2+]i in fission yeast is maintained at a physiologic level when [Mg2+]o is low, but intracellular free Mg2+ rapidly rises when [Mg2+]o is elevated. Like most eukaryotic cells, yeast may have a Mg2+ transport system(s) which functions to maintain gradients of Mg2+ from the outside to inside the cell and among its subcellular compartments.
Received 18 April 1996; received after revision 4 July 1996; accepted 26 July 1996 相似文献
18.
The superoxide-generating NADPH oxidase: structural aspects and activation mechanism 总被引:31,自引:0,他引:31
Vignais PV 《Cellular and molecular life sciences : CMLS》2002,59(9):1428-1459
Flavocytochrome b
558
is the catalytic core of the respiratory-burst oxidase, an enzyme complex that catalyzes the NADPH-dependent reduction of
O2 into the superoxide anion O2
- in phagocytic cells. Flavocytochrome b
558
is anchored in the plasma membrane. It is a heterodimer that consists of a large glycoprotein gp91phox (phox for phagocyte oxidase) (β subunit) and a small protein p22phox (α subunit). The other components of the respiratory-burst oxidase are water-soluble
proteins of cytosolic origin, namely p67phox, p47phox, p40phox and Rac. Upon cell stimulation, they assemble with the membrane-bound
flavocytochrome b
558
which becomes activated and generates O2
-. A defect in any of the genes encoding gp91phox, p22phox, p67phox or p47phox results in chronic granulomatous disease, a
genetic disorder characterized by severe and recurrent infections, illustrating the role of O2
- and the derived metabolites H2O2 and HOCl in host defense against invading microorganisms. The electron carriers, FAD and hemes b, and the binding site for NADPH are confined to the gp91phox subunit of flavocytochrome b
558
. The p22phox subunit serves as a docking site for the cytosolic phox proteins. This review provides an overview of current
knowledge on the structural organization of the O2
--generating flavocytochrome b
558
, its kinetics, its mechanism of activation and the regulation of its biosynthesis. Homologues of gp91phox, called Nox and
Duox, are present in a large variety of non-phagocytic cells. They exhibit modest O2
--generating oxidase activity, and some act as proton channels. Their role in various aspects of signal transduction is currently
under investigation and is briefly discussed.
Received 28 May 2002; received after revision 20 June 2002; accepted 24 June 2002 相似文献
19.
R.E. Williamson J.E. Burn C.H. Hocart 《Cellular and molecular life sciences : CMLS》2001,58(10):1475-1490
Cellulose microfibrils containing crystalline β-1,4-glucan provide the major structural framework in higher-plant cell walls. Genetic analyses of Arabidopsis thaliana now link specific genes to plant cellulose production just as was achieved some years earlier with bacteria. Cellulose-deficient
mutants have defects in several members of one family within a complex glycosyltransferase superfamily and in one member of
a small family of membrane-bound endo-1,4-β-glucanases. The mutants also accumulate a readily extractable β-1,4-glucan that has short chains which, in at least one case, are lipid linked. Cellulose could be made by direct extension
of the glucan chain by the glycosyltransferase or, as the mutant suggests, by an indirect route which makes lipid-linked oligosaccharides.
Models discussed incorporate the known enzymes and lipo-glucan and raise the possibility that different CesA glycosyltransferases
may catalyse different steps.
Received 5 January 2001; received after revision 25 April 2001; accepted 25 April 2001 相似文献
20.
Culture in low levels of oxygen enhances in vitro proliferation potential of satellite cells from old skeletal muscles 总被引:4,自引:0,他引:4
Chakravarthy MV Spangenburg EE Booth FW 《Cellular and molecular life sciences : CMLS》2001,58(8):1150-1158
The proliferation ability of satellite cells (considered the 'stem cells' of mature myofibers) declines with increasing age
when cultured under standard cell culture conditions of 21% oxygen. However, actual oxygen levels in the intact myofiber in
vivo are an order of magnitude lower. No studies to date have addressed the issue of whether culturing satellite cells from
old muscles under more 'physiologic' conditions would enhance their proliferation and/or differentiation ability. Therefore,
we analyzed satellite cells derived from 31-month-old rats in standard cultures with 21% O2 and in lowered (∼3%) O2. Under the lowered O2 conditions, we noted a remarkable increase in the percentage of large-sized colonies, activation of cell cycle progression
factors, phosphorylation of Akt, and downregulation of the cell cycle inhibitor p27Kip1. These data suggest that lower O2 levels provide a milieu that stimulates proliferation by allowing continued cell cycle progression, to result ultimately
in the enhanced in vitro replicative life span of the old satellite cells. Such a method therefore provides an improved means
for the ex vivo generation of progenitor satellite cell populations for potential therapeutic stem cell transplantation.
Received 20 April 2001; received after revision 28 May 2001; accepted 31 May 2001 相似文献