共查询到20条相似文献,搜索用时 31 毫秒
1.
Summary. This paper examines a unique hypothesis regarding an important role for taurine in renal development. Taurine-deficient neonatal
kittens show renal developmental abnormalities, one of several lines of support for this speculation. Adaptive regulation
of the taurine transporter gene is critical in mammalian species because maintenance of adequate tissue levels of taurine
is essential to the normal development of the retina and the central nervous system. Observations of the remarkable phenotypic
similarity that exists between children with deletion of bands p25-pter of chromosome 3 and taurine-deficient kits led us
to hypothesize that deletion of the renal taurine transporter gene (TauT) might contribute to some features of the 3p-syndrome.
Further, the renal taurine transporter gene is down-regulated by the tumor suppressor gene p53, and up-regulated by the Wilms
tumor (WT-1) and early growth response-1 (EGR-1) genes. It has been demonstrated using WT-1 gene knockout mice that WT-1 is
critical for normal renal development. In contrast, transgenic mice overexpressing the p53 gene have renal development defects,
including hypoplasia similar to that observed in the taurine-deficient kitten. This paper reviews evidence that altered expression
of the renal taurine transporter may result in reduced intracellular taurine content, which in turn may lead to abnormal cell
volume regulation, cell death and, ultimately, defective renal development.
Received January 25, 2000/Accepted January 31, 2000 相似文献
2.
Trog D Moenkemann H Breipohl W Schueller H Schild H Golubnitschaja O 《Amino acids》2007,32(3):373-379
Summary.
Objectives. Human gliomas have a catastrophic prognosis with a median survival in the range of one year even after therapeutic treatment.
Relatively high resistance towards apoptotic stimuli is the characteristic feature of malignant gliomas. Since cell cycle
control has been shown to be the key mechanism controlling both apoptosis and proliferation, this study focuses on DNA damage
analysis and protein expression patterns of essential cell cycle regulators P53 and P21waf1/cip1 in glioma under clinically relevant therapeutic conditions.
Material and methods. U87MG cell line, characterised by wild p53-phenotype relevant for the majority of primary malignant glioblastomas, was used. Glioma cells underwent either irradiation
or temozolomide treatment alone, or combined radio/chemo treatment. DNA damage was analysed by the “Comet Assay”. Expression
rates of target proteins were analysed using “Western-Blot” technique.
Results and conclusions. “Comet Assay” demonstrated extensive DNA damage caused by temozolomide treatment alone and in combination with irradiation,
correlating well with the low survival rate observed under these treatment conditions. In contrast, irradiation alone resulted
in a relatively low DNA damage, correlating well with a high survival rate and indicating a poor therapeutic efficiency of
irradiation alone. Unusually low up-regulation of P53 and P21waf1/cip1 expression patterns was produced by the hereby tested stressful conditions. A deficit in cell cycle control might be the
clue to the high resistance of malignant glioma cells to established therapeutic approaches. 相似文献
3.
4.
Unahara Y Kojima-Yuasa A Higashida M Kennedy DO Murakami A Ohigashi H Matsui-Yuasa I 《Amino acids》2007,33(3):469-476
Summary. 1′-Acetoxychavicol acetate (ACA) has been shown to inhibit tumor cell growth, but there is limited information on its effects
on cell signaling and the cell cycle control pathway. In this study, we sought to determine how ACA alters cell cycle and
its related control factors in its growth inhibitory effect in Ehrlich ascites tumor cells (EATC). ACA caused an accumulation
of cells in the G1 phase and an inhibition of DNA synthesis, which were reversed by supplementation with N-acetylcysteine
(NAC) or glutathione ethyl ester (GEE). Furthermore, ACA decreased hyperphosphorylated Rb levels and increased hypophosphorylated
Rb levels. NAC and GEE also abolished the decease in Rb phosphorylation by ACA. As Rb phosphorylation is regulated by G1 cyclin
dependent kinase and CDK inhibitor p27kip1, which is an important regulator of the mammalian cell cycle, we estimated the amount of p27kip1 levels by western blotting. Treatment with ACA had virtually no effect on the amount of p27kip1 levels, but caused a decrease in phosphorylated p27kip1 and an increase in unphosphorylated p27kip1 as well as an increase in the nuclear localization of p27kip1. These events were abolished in the presence of NAC or GEE. These results suggest that in EATC, cell growth inhibition elicited
by ACA involves decreases in Rb and p27kip1 phosphorylation and an increase in nuclear localization of p27kip1, and these events are dependent on the cellular thiol status. 相似文献
5.
Pawelke B 《Amino acids》2005,29(4):377-388
Summary. Substances of various chemical structures can be labelled with appropriate positron emitting isotopes and applied as tracer
compounds in PET examinations. Using dynamic data acquisition protocols, time-activity curves of radioactivity uptake in organs
can be derived and the measurements of tissue tracer concentrations can be translated into quantitative values of tissue function.
However, analysis of metabolites of these tracers regarding their nature and distribution in the living organism is an essential
need for the quantitative analysis of PET measurements. In addition, metabolite analysis contributes to the interpretation
of the images obtained as well as to the identification of pathological changes in metabolic pathways. This paper reports
on representative examples of radiolabelled compounds which might be of importance in food science (e.g., amino acids, polyphenols,
and model compounds for advanced glycation end products (AGEs)). Typical procedures of analysis (radio-HPLC, radio-TLC) including
pre-analytical sample preparation are described. Specific challenges of the method, e.g., trace amounts of radiolabelled compounds
and the influence of the often very short half-lives of positron-emitting nuclides used are highlighted. Representative results
of analyses of plasma, urine, and tissue samples are presented and discussed in terms of the metabolic fate of the tracers. 相似文献
6.
p53 mutations are frequently found in human cancers and are often associated with the overexpression of wild-type (WT) protein or peptide sequences, supporting the notion that WT p53 epitopes may serve as potential targets for tumor immunotherapy. We have developed a cytotoxic T lymphocyte (CTL)/p53 tumor-associated antigen (TAA) model, based on immune recognition of a WT p53 determinant. WT p53-peptide-specific, major histocompatibility complex (MHC) classI-restricted CTL were produced from immunocompetent C57BL/6 (H-2b) mice after immunization with a previously defined WT p53 peptide (p53(232-240)) Epitope-specific CTL were then employed to identify syngeneic tumor cell populations expressing that antigenic determinant. Two syngeneic tumor cell lines, MC38 colon carcinoma and MC57G fibrosarcoma, were demonstrated to express the endogenous WT p53(232-240) determinant naturally, as defined by CD8 + CTL recognition. Cold-target inhibition assays confirmed that CTL-mediated lysis was due to immune recognition of the p53(232-240) peptide epitope. The p53(232-240)-specific CTL line did not lyse syngeneic normal cells (i.e., mitogen-activated splenocytes) in the absence of exogenous peptide, suggesting that the WT-p53-specific CTL could distinguish between tumor cells expressing self-TAA and normal host cells. We have demonstrated, for the first time, that the adoptive transfer of WT-p53-specific CTL to mice with established pulmonary metastasis resulted in antitumor activity in vivo. The ability to generate MHC-class-I-restricted CD8- CTL lines specific for a non-mutated p53 determinant from normal, immunocompetent mice, which display antitumor activity both in vitro and in vivo (by adoptive transfer), may have implications for the immunotherapy of certain p53-expressing malignancies. 相似文献
7.
Programmed cell death: similarities and differences in animals and plants. A flower paradigm 总被引:1,自引:0,他引:1
Summary. After an overview of the criteria for the definition of cell death in the animal cell and of its different types of death,
a comparative analysis of PCD in the plant cell is reported. The cytological characteristics of the plant cell undergoing
PCD are described.
The role of plant hormones and growth factors in the regulation of this event is discussed with particular emphasis on PCD
activation or prevention by polyamine treatment (doses, timing and developmental stage of the organism) in a Developmental
cell death plant model: the Nicotiana tabacum (tobacco) flower corolla. Some of the effects of polyamines might be mediated by transglutaminase catalysis. The activity
of this enzyme was examined in different parts of the corolla during its life span showing an acropetal trend parallel to
the cell death wave. The location of transglutaminase in some sub-cellular compartments suggests that it exerts different
functions in the corolla DCD. 相似文献
8.
Dickinson RB 《Journal of mathematical biology》2000,40(2):97-135
A generalized transport model is derived for cell migration in an anisotropic environment and is applied to the specific
cases of biased cell migration in a gradient of a stimulus (taxis; e.g., chemotaxis or haptotaxis) or along an axis of anisotropy (e.g., contact guidance). The model accounts for spatial or directional dependence of cell speed and cell turning behavior to predict a constitutive
cell flux equation with drift velocity and diffusivity tensor (termed random motility tensor) that are explicit functions of the parameters of the underlying random walk model. This model provides the connection between
cell locomotion and the resulting persistent random walk behavior to the observed cell migration on longer time scales, thus
it provides a framework for interpreting cell migration data in terms of underlying motility mechanisms.
Received: 8 April 1999 相似文献
9.
Homma H 《Amino acids》2007,32(1):3-11
Summary. Recent investigations have shown that D-aspartate (D-Asp) plays an important physiological role(s) in the mammalian body.
Here, several recent studies of free D-Asp metabolism in mammals, focusing on cellular localization in tissues, intracellular
localization, biosynthesis, efflux, uptake and degradation are reviewed.
D-Asp in mammalian tissues is present in specific cells, indicating the existence of specific molecular components that regulate
D-Asp levels and localization in tissues. In the rat pheochromocytoma cell line (PC12) and its subclones, D-Asp is synthesized
intracellularly, most likely by Asp racemase(s). Endogenous D-Asp apparently has two different intracellular localization
patterns: cytoplasmic and vesicular. In PC12 cells, D-Asp release can occur through three distinct pathways: 1) spontaneous,
continuous release of cytoplasmic D-Asp, which is not associated with a specific stimulus; 2) release of cytoplasmic D-Asp
via a volume-sensitive organic anion channel that connects the cytoplasm and extracellular space; 3) exocytotic discharge
of vesicular D-Asp. Under certain conditions, D-Asp can be released via a mechanism that involves the L-Glu transporter. D-Asp
is thus apparently in dynamic flux at the cellular level to carry out its physiological function(s) in mammals. 相似文献
10.
We derive from the age-structured model a system of delay differential equations to describe the interaction of spatial dispersal (over two patches) and time delay (arising from the maturation period). Our model analysis shows that varying the immature death rate can alter the behavior of the homogeneous equilibria, leading to transient oscillations around an intermediate equilibrium and complicated dynamics (in the form of the coexistence of possibly stable synchronized periodic oscillations and unstable phase-locked oscillations) near the largest equilibrium. 相似文献
11.
12.
Summary. Tuberous sclerosis (TSC) is an autosomal dominantly inherited disease affecting 1 in 6000 individuals. The TSC gene products,
hamartin and tuberin, form a complex, of which tuberin is assumed to be the functional component being involved in a wide
variety of different cellular processes. Tuberin has been demonstrated to be localized to both, the cytoplasm and the nucleus.
The cytoplasmic/nuclear localization of tuberin is known to be regulated by the serine/threonine protein kinase Akt. Akt also
regulates the cytoplasmic/nuclear localization of the cyclin-dependent kinase inhibitor p27. In this study the localization
of these two Akt-regulated proteins was analysed in different cell lines. 相似文献
13.
Summary. A series of polyamine conjugates were synthesized and evaluated for their ability to target the polyamine transporter (PAT)
in two Chinese hamster ovary (CHO) cell lines (PAT-active CHO and PAT-inactive CHOMG). This systematic study identified salient
features of the polyamine architecture required to target and enter cells via the PAT. Indeed, the separation of charges,
the degree of N-alkylation, and the spacer unit connecting the N1-terminus to the appended cytotoxic component (anthracene) were found to be key contributors to optimal delivery via the PAT.
Using the CHO screen, the homospermidine motif (e.g., 4,4-triamine) was identified as a polyamine vector, which could enable
the selective import of large N1-substituents (i.e., naphthylmethyl, anthracenylmethyl and pyrenylmethyl), which were cytotoxic to cells. The cell selectivity
of this approach was demonstrated in B-16 murine melanoma cells and normal melanocytes (Mel-A). Three polyamine areas (recognition
and transport, vesicle sequestration and polyamine-target interactions) were identified for future research. 相似文献
14.
Summary. The effect of α-difluoromethylornithine (DFMO) on the apoptosis of HC11 mouse mammary epithelial cells was investigated.
The involvement of reactive oxygen species (ROS) and Bcl-2 protein in the mechanism of apoptosis induced by ornithine decarboxylase
(ODC) inhibition was also assessed. DFMO (0.1, 1 and 5 mM) induced apoptosis of HC11 cells in dose- and time-dependent manner.
Apoptosis manifests itself with morphological features like: cell shrinkage, condensation of chromatin, pyknosis and fragmentation
of nucleus, followed by secondary necrosis (putrosis). The decrease in the nuclear DNA contents appearing as the hypodiploidal
peak sub-G1 in the DNA histogram was not dependent on the presence of prolactin (5 μg/ml) in DFMO-treated cultures. Apoptosis induced
by ODC inhibition was associated with a rapid increase in ROS concentration in HC11 cells observed within 1 h after DFMO treatment.
The down-regulation of Bcl-2 as a decrease in cell number expressing bcl-2 and a lowered Bcl-2 protein content in cells expressing this protooncogene was also noted. The administration of putrescine
(50 μM) lowered the number of early-apoptotic, late-apoptotic and necrotic cells. Moreover, it increased the number of cells
expressing bcl-2. In conclusion, the disturbance of cellular polyamine homeostasis by inhibition of their synthesis enhances mammary epithelial
cell susceptibility to apoptosis. It may occur in the mammary gland at the end of lactation, when the depletion of circulating
lactogenic hormones and activation of intra-mammary apoptogenic factors expression take place.
Received May 6, 1999; Accepted December 15, 1999 相似文献
15.
The rate of expansion of bacterial colonies of S. liquefaciens is investigated in terms of a mathematical model that combines biological as well as hydrodynamic processes. The relative
importance of cell differentiation and production of an extracellular wetting agent to bacterial swarming is explored using
a continuum representation. The model incorporates aspects of thin film flow with variable suspension viscosity, wetting,
and cell differentiation. Experimental evidence suggests that the bacterial colony is highly sensitive to its environment
and that a variety of mechanisms are exploited in order to proliferate on a variety of surfaces. It is found that a combination
of effects are required to reproduce the variation of bacterial colony motility over a large range of nutrient availability
and medium hardness.
Received: 29 April 1999 相似文献
16.
Parametric analysis of the ratio-dependent predator–prey model 总被引:3,自引:0,他引:3
We present a complete parametric analysis of stability properties and dynamic regimes of an ODE model in which the functional response is a function of the ratio of prey and predator abundances. We show the existence of eight qualitatively different types of system behaviors realized for various parameter values. In particular, there exist areas of coexistence (which may be steady or oscillating), areas in which both populations become extinct, and areas of "conditional coexistence" depending on the initial values. One of the main mathematical features of ratio-dependent models, distinguishing this class from other predator-prey models, is that the Origin is a complicated equilibrium point, whose characteristics crucially determine the main properties of the model. This is the first demonstration of this phenomenon in an ecological model. The model is investigated with methods of the qualitative theory of ODEs and the theory of bifurcations. The biological relevance of the mathematical results is discussed both regarding conservation issues (for which coexistence is desired) and biological control (for which extinction is desired). 相似文献
17.
It is well accepted that neo-vascular formation can be divided into three main stages (which may be overlapping): (1) changes
within the existing vessel, (2) formation of a new channel, (3) maturation of the new vessel.
In this paper we present a new approach to angiogenesis, based on the theory of reinforced random walks, coupled with a Michaelis-Menten
type mechanism which views the endothelial cell receptors as the catalyst for transforming angiogenic factor into proteolytic
enzyme in order to model the first stage. In this model, a single layer of endothelial cells is separated by a vascular wall
from an extracellular tissue matrix. A coupled system of ordinary and partial differential equations is derived which, in
the presence of an angiogenic agent, predicts the aggregation of the endothelial cells and the collapse of the vascular lamina,
opening a passage into the extracellular matrix. We refer to this as the onset of vascular sprouting. Some biological evidence
for the correctness of our model is indicated by the formation of teats in utero. Further evidence for the correctness of
the model is given by its prediction that endothelial cells will line the nascent capillary at the onset of capillary angiogenesis.
Received: 27 May 1999 / Revised version: 28 December 1999 / Published online: 16 February 2001 相似文献
18.
Lentini A Provenzano B Caraglia M Shevchenko A Abbruzzese A Beninati S 《Amino acids》2008,34(2):251-256
Summary. Previously published evidences highlighted the effect of transglutaminase (TG, EC 2.3.2.13) activation on the reduction of
the in vitro adhesive and invasive behaviour of murine B16-F10 melanoma cells, as well as in vivo. Here, we investigated the
influence of spermidine (SPD) incorporation by TG into basement membrane components i.e. laminin (LN) or Matrigel (MG), on
the adhesion and invasion of B16-F10 melanoma cells by these TG/SPD-modified substrates. The adhesion assays showed that cell
binding to the TG/SPD-modified LN was reduced by 30%, when compared to untreated LN, whereas the reduction obtained using
TG/SPD-modified MG was 35%. Similarly, tumor cell invasion by the Boyden chamber system through TG/SPD modified LN or MG was
respectively reduced by 45%, and by 69%. Evaluation of matrix metalloproteinase (gelatinases MMP-2 and MMP-9) activities by
gel-zymography showed that MMP-2 activity was unaffected, while MMP-9 activity was reduced by about 32% using TG/SPD-modified
substrate. These results strongly suggest that the observed antiinvasive effect of TG activation in the host may be ascribed
to the covalent incorporation of polyamines, which led to the post-translational modification of some components of the cell
basement membrane. This modification may interfere with the metastatic property of melanoma cells, affecting the proteolytic
activity necessary for their migration and invasion activities.
Authors’ address: Simone Beninati, Department of Biology, University of Rome “Tor Vergata”, Via della Ricerca Scientifica,
I-00133 Rome, Italy 相似文献
19.
Summary. Effects of testosterone (10 μg/100 g body weight) on polyamine-oxidizing enzyme activities in female rat uterus, liver and kidney were demonstrated. Testosterone-treated
rats exhibited 2.07 fold (p < 0.002) higher uterine polyamine oxidase (PAO) activity and 1.93 fold (p < 0.02) higher diamine
oxidase (DAO) activity, as compared to the controls. In the liver, testosterone caused an elevation in PAO (1.39 fold, p <
0.05), but not in DAO activity, whereas in kidney the hormone stimulated DAO (1.30 fold, p < 0.05), but not PAO activity.
The effects observed suggest a possible role for testosterone in the modulation of polyamine levels in the female organs studied
and especially in uterus.
Received May 12, 1999, Accepted December 16, 1999 相似文献
20.
Summary. The influence of nitric oxide synthase (NOS) activity on the KCl-evoked amino acid concentrations was investigated by in vivo microdialysis in the striatum in a rat model of excitotoxic lesion. Basal microdialysate levels of amino acids decreased
during the quinolinic acid-induced neurodegeneration process, except for glutamine that increased initially and returned to
control values 30 days after quinolinic acid exposure. KCl-evoked increase of extracellular amino acid concentration was reduced
due to NOS activity in the striatum of both controls and lesioned animals, except for 120 days after quinolinic acid injection.
These changes of amino acid concentrations in microdialysates correlated with the known biochemistry of the consecutive domineered
cell types during the lesion process as revealed by histochemistry for NOS, NADPH-diaphorase, GFAP and isolectin B4. The present
data provide direct evidence that NOS activity can modulate extracellular amino acid concentrations in the striatum not only
under physiological conditions, but also during a pharmacologically induced lesion process and, thus, suggests that nitric
oxide affects neurodegeneration via this pathway.
Received October 20, 1999; Accepted February 25, 2000 相似文献