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1.
Polyamines and abiotic stress: recent advances 总被引:8,自引:0,他引:8
Summary. In this review we will concentrate in the results published the last years regarding the involvement of polyamines in the
plant responses to abiotic stresses, most remarkably on salt and drought stress. We will also turn to other types of abiotic
stresses, less studied in relation to polyamine metabolism, such as mineral deficiencies, chilling, wounding, heavy metals,
UV, ozone and paraquat, where polyamine metabolism is also modified.
There is a great amount of data demonstrating that under many types of abiotic stresses, an accumulation of the three main
polyamines putrescine, spermidine and spermine does occur. However, there are still many doubts concerning the role that polyamines
play in stress tolerance. Several environmental challenges (osmotic stress, salinity, ozone, UV) are shown to induce ADC activity
more than ODC. The rise in Put is mainly attributed to the increase in ADC activity as a consequence of the activation of
ADC genes and their mRNA levels. On the other hand, free radicals are now accepted as important mediators of tissue injury
and cell death. The polycationic nature of polyamines, positively charged at physiological pH, has attracted the attention
of researchers and has led to the hypothesis that polyamines could affect physiological systems by binding to anionic sites,
such as those associated with nucleic acids and membrane phospholipids. These amines, involved with the control of numerous
cellular functions, including free radical scavenger and antioxidant activity, have been found to confer protection from abiotic
stresses but their mode of action is not fully understood yet. In this review, we will also summarize information about the
involvement of polyamines as antioxidants against the potential abiotic stress-derived oxidative damage.
Authors’ address: Dr. María Patricia Benavides, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956,
Buenos Aires 1113, Argentina 相似文献
2.
Innate immunity and nutrient metabolism are complex biological systems that must work in concert to sustain and preserve life. The effector cells of the innate immune system rely on essential nutrients to generate energy, produce metabolic precursors for macromolecule biosynthesis and tune their responses to infectious agents. Thus disruptions to nutritional status have a substantial impact on immune competence and can result in increased susceptibility to infection in the case of nutrient deficiency, or chronic inflammation in the case of over-nutrition. The traditional, reductionist methods used in the study of nutritional immunology are incapable of exploring the extremely complex interactions between nutrient metabolism and innate immunity. Here, we review a relatively new analytical approach, systems biology, and highlight how it can be applied to nutritional immunology to provide a comprehensive view of the mechanisms behind nutritional regulation of the innate immune system. 相似文献
3.
Summary. Aliphatic polyamines have generally been measured on the whole kidney. Since the kidney is composed of a variety of cells,
whole organ data are of limited value for the interpretation of the functions of the polyamines. The aim of this study was
to establish the distribution pattern of putrescine, spermidine and spermine within the kidneys of male and female rats and
rabbits. It is shown that the polyamines are unevenly distributed along the cortico-papillary axis. Each amine exhibited its
own distinct distribution pattern. The polyamines are predominantly located in the cortex. Putrescine levels increased gradually
from the cortex to the papillary tip in rabbits, whereas, in rats, fluctuations in putrescine level were marked. In the six
zones of the rabbit kidney studied, spermidine and spermine concentrations were markedly higher in females than in males.
This difference was less marked in rats.
Received April 1, 1999, Accepted May 17, 1999 相似文献
4.
Summary. The relationship between cellular glutathione (GSH), protein-SH levels, and lactate dehydrogenase (LDH), with respect to
the effect of polyamines on the cytoprotective ability of L-cysteine and L-methionine, the most important components in the
sulfur amino acid metabolic pathway, in carbon tetrachloride (CCl4)-induced toxicity in isolated rat hepatocytes was studied. CCl4 induced a LDH release and decreased cellular thiols and polyamines levels but treatment with L-cysteine and L-methionine
reversed these decreases. Treating with methylglyoxal bis-(guanylhydrazone), MGBG, an irreversible inhibitor of S-adenosylmethionine
decarboxylase, which is a key enzyme in spermidine and spermine biosynthesis, and therefore used to deplete cellular polyamines,
prevented the protective effect of L-cysteine and L-methionine, but the addition of exogenous polyamines inhibited the influence
of MGBG. These results suggest that the cytoprotective effect of L-cysteine and L-methionine in CCl4-induced toxicity were via maintenance of cellular polyamines, GSH and protein-SH concentrations and prevention of LDH leakage.
Received September 1, 1999, Accepted January 11, 2000 相似文献
5.
Summary. The effect of different doses of cadmium and copper was studied in relation to growth and polyamine (Pas) metabolism in shoots
of sunflower plants. Cadmium accumulated to higher levels than copper and shoot length was reduced by 0.5 and 1 mM Cd, but
only by 1 mM Cu. At 1 mM of Cd or Cu, Put content increased 270% and 160% with Cd2+ and Cu2+, respectively. Spermidine (Spd) was modified only by 1 mM Cd, while spermine (Spm) declined after seeds germinated, increasing
thereafter but only with 1 mM Cd or Cu (273% over the controls for Cd and 230% for Cu at day 16). Both ADC and ODC activities
were increased by 1 mM Cd, whereas 1 mM Cu enhanced ADC activity, but reduced ODC activity at every concentration used. The
role of Pas as markers of Cd or Cu toxicity is discussed. 相似文献
6.
Summary. The levels of polyamines (putrescine, spermidine and spermine) and polyamine oxidase in plasma of patients with chronic renal
failure were determined. The level of putrescine was increased but the level of spermine was decreased in the plasma of these
patients. The patients also had increased plasma polyamine oxidase activity leading to increased degradation of spermine.
As acrolein was a major toxic compound produced from spermine by polyamine oxidase, the levels of free and protein-conjugated
acrolein in plasma were also measured. Acrolein levels were enhanced in plasma of patients with chronic renal failure. The
accumulated acrolein found as protein conjugates was equivalent to 170 μM, which was about 5-fold higher than in plasma of
normal subjects. It was found that acrolein is mainly produced by spermine oxidase in plasma. An increase in putrescine, spermine
oxidase and acrolein in plasma was observed in all cases such as diabetic nephropathy, chronic glomerulonephritis and nephrosclerosis.
After patients with chronic renal failure had undergone hemodialysis, their levels of plasma polyamines, spermine oxidase
and acrolein returned towards normal. It is likely that acrolein produced from spermine accumulates in the blood due to decreased
excretion into urine and may function as a uremic “toxin”. 相似文献
7.
Advances in systems biology are enhancing our understanding of disease and moving us closer to novel disease treatments 总被引:2,自引:0,他引:2
With tens of billions of dollars spent each year on the development of drugs to treat human diseases, and with fewer and fewer
applications for investigational new drugs filed each year despite this massive spending, questions now abound on what changes
to the drug discovery paradigm can be made to achieve greater success. The high rate of failure of drug candidates in clinical
development, where the great majority of these drugs fail due to lack of efficacy, speak directly to the need for more innovative
approaches to study the mechanisms of disease and drug discovery. Here we review systems biology approaches that have been
devised over the last several years to understand the biology of disease at a more holistic level. By integrating a diversity
of data like DNA variation, gene expression, protein–protein interaction, DNA–protein binding, and other types of molecular
phenotype data, more comprehensive networks of genes both within and between tissues can be constructed to paint a more complete
picture of the molecular processes underlying physiological states associated with disease. These more integrative, systems-level
methods lead to networks that are demonstrably predictive, which in turn provides a deeper context within which single genes
operate such as those identified from genome-wide association studies or those targeted for therapeutic intervention. The
more comprehensive views of disease that result from these methods have the potential to dramatically enhance the way in which
novel drug targets are identified and developed, ultimately increasing the probability of success for taking new drugs through
clinical development. We highlight a number of the integrative approaches via examples that have resulted not only in the
identification of novel genes for diabetes and cardiovascular disease, but in more comprehensive networks as well that describe
the context in which the disease genes operate. 相似文献
8.
Summary. Glucocorticoids are potent anti-inflammatory and immunosuppressive agents. As endogenous inhibitors of cytokine synthesis,
glucocorticoids suppress immune activation and uncontrolled overproduction of cytokines, preventing tissue injury. Also, polyamine
spermine is endogenous inhibitor of cytokine production (inhibiting IL-1, IL-6 and TNF synthesis). The idea of our work was
to examine dexamethasone effects on the metabolism of polyamines, spermine, spermidine and putrescine and polyamine oxidase
activity in liver and spleen during sensitization of guinea pigs. Sensitization was done by application of bovine serum albumin
with addition of complete Freund’s adjuvant. Our results indicate that polyamine amounts and polyamine oxidase activity increase
during immunogenesis in liver and spleen. Dexamethasone application to sensitized and unsensitized guinea pigs causes depletion
of polyamines in liver and spleen. Dexamethasone decreases polyamine oxidase activity in liver and spleen of sensitized guinea
pigs, increasing at the same time PAO activity in tissues of unsensitized animals. 相似文献
9.
Bonsi P Cuomo D Picconi B Sciamanna G Tscherter A Tolu M Bernardi G Calabresi P Pisani A 《Amino acids》2007,33(2):189-195
Summary. Polyamine metabolic genes are downstream targets of several genes commonly mutated in colon adenomas and cancers. Inhibitors
of ornithine decarboxylase, such as difluoromethylornithine (DFMO), and agents that stimulate polyamine acetylation and export,
such as non-steroidal anti-inflammatory drugs (NSAIDS), act at least additively to arrest growth in human cell models and
suppress intestinal carcinogenesis in mice. These preclinical studies provided the rationale for colon cancer prevention trials
in humans. A Phase IIb clinical study comparing the combination of DFMO and the NSAID sulindac versus placebo was conducted.
Endpoints were colorectal tissue polyamine and prostaglandin E2 contents and overall toxicity to participants. Participants
in the Phase IIb study served as a vanguard for a randomized, placebo-controlled prospective Phase III trial of the combination
of DFMO and sulindac with the primary study endpoint the prevention of colon polyps. Seventy percent of participants will
have completed the three years of treatment in December 2006. 相似文献
10.
11.
近十年来,生理学与基因组学达到了空前的融合。尽管生理基因组学还是一个非常年轻的研究领域,系统生物学概念的引入必将推进生理基因组学达到全新的水平。本文概要地叙述了这个令人振奋的生理科学的新时代给生理学家带来的机遇和挑战,并以我们自己近十年来的经验为例,讨论了怎样通过扩展和延伸生理学与基因组学的结合,从而对生物学得到系统的理解。 相似文献
12.
Antizyme and antizyme inhibitor activities influence cellular responses to polyamine analogs 总被引:1,自引:0,他引:1
Summary. Close structural analogs of spermidine and spermine, polyamine mimetics, are potential chemotheraputic agents as they depress
cellular polyamines required for tumor growth. Specific mimetic analogs stimulate synthesis of the regulatory protein antizyme
(AZ), which not only inactivates the initial enzyme in polyamine biosynthesis but also inhibits cellular uptake of polyamines.
The role of AZ induction in influencing cellular uptake of representative analogs was investigated using three analogs produced
by Cellgate Inc., CGC-11047, CGC-11102, and CGC-11144, which exhibit markedly distinct AZ-inducing potential. An inverse correlation
was noted between the AZ-inducing activity of a compound and the steady-state levels accumulated in cells. As some tumor cells
over express AZI as a means of enhancing the polyamines required for aggressive growth, analog sensitivity was examined in
transgenic CHO cells expressing exogenous antizyme inhibitor protein (AZI). Although AZI over expression increased cell sensitivity
to analogs, the degree of this affect varied with the analog used. 相似文献
13.
Summary. Mammalian hexokinase (HXK) is found at the outer mitochondrial membrane, exposed to mitochondrial oxygen- and nitrogen-radicals.
Given the important role of this enzyme in metabolic pathways and diseases, the effect of S-nitrosoglutathione (GSNO) on HXK A structure and activity was studied. To focus on the catalytic domain, yeast HXK A was
used because it has a significant homology to the mammalian domain that contains both the regulatory and catalytic sites.
Biologically relevant [GSNO]/[HXK] caused a significant decrease in Vmax with glucose (but not with fructose), along with oxidation of 5 Met and nitration of 4 Tyr. Preincubation of HXK with glucose
abrogated the effect of GSNO whereas fructose was ineffective. These results are interpreted by considering the tight binding
of glucose to the enzyme as opposed to that of fructose. The segment comprised from amino acids 304 to 306 contained the most
modifications. Given that this sequence is highly conserved in HXK from various species, a decline in activity is expected
when a high-affinity substrate is presented.
Considering that changes in primary structure are envisioned at high [GSNO]/[HXK] ratios, like those present under normal
conditions, it could be hypothesized that the high concentration of hexokinase present in fast growing tumors may serve not
only to sustain high glycolysis rates, but also to minimize protein damage that might result in activity decline, compromising
energy metabolism. 相似文献
14.
Summary. The in vitro and in vivo effects of two flavonons, naringenin (NG) and hesperitin (HP) on the proliferation rate of highly metastatic murine B16-F10
melanoma cell were investigated. NG or HP treatment of melanoma cells produced a remarkable reduction of cell proliferation,
paralleled with both the lowering of the intracellular levels of polyamine, spermidine and spermine and the enhancement of
transglutaminase (TGase, EC 2.3.2.13) activity. Orally administered NG or HP in C57BL6/N mice inoculated with B16-F10 cells
affected the pulmonary invasion of melanoma cells in an in vivo metastatic assay. The number of lung metastases detected by a computerized image analyzer was reduced, compared to untreated
animals, by about 69% in NG-treated mice and by about 36% in HP-treated mice. Survival studies showed that 50% of the NG-treated
animals died 38 ± 3.1 days after tumor cell injection (control group: 18 ± 1.5 days) and HP-treated mice died 27 ± 2.3 days
after cell inoculation. Taken together, these findings provide further evidences for the potential anticancer properties of
dietary flavonoids as chemopreventive agents against malignant melanoma. 相似文献
15.
16.
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
17.
18.
Sved DW Godsey JL Ledyard SL Mahoney AP Stetson PL Ho S Myers NR Resnis P Renwick AG 《Amino acids》2007,32(4):459-466
Summary. Three biodisposition studies with taurine were performed in male and female adult rats at dosages of 30 and 300 mg/kg. A single
oral dose of 14C-taurine was rapidly absorbed, distributed to tissues and excreted unchanged in urine. Elimination of radioactivity from
intracellular pools was slow. Pre-treatment of animals for 14 days with unlabelled taurine did not significantly affect the
fate of 14C-taurine. At the higher dose there was more extensive excretion combined with a lower percentage of the dose in the carcass,
indicating the possibility of saturation of the tubular reabsorption mechanism for taurine. Daily administration of unlabelled
taurine for 14 days did not result in an increase in total taurine in the brain. The data indicate that exogenous taurine
rapidly equilibrates with endogenous body pools and that any excess is rapidly eliminated by the kidneys. 相似文献
19.
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
20.
Summary. Gamma-aminobutyric acid (GABA) is considered to be a multifunctional molecule with various physiological effects throughout
the body. It is also evident that the liver contains GABA and its transporter. However, the functions of GABA in liver have
not been well documented. In this study, the cytoprotective effect of GABA against ethanol-induced hepatotoxicity was evaluated
in primary cultured rat hepatocytes. Addition of ethanol induced decrease of cell viability in a dose-dependent manner. However,
treatment with GABA resulted in a dose-dependent recovery from ethanol (150 mM)-induced cytotoxicity.
GABA reversed the ethanol-induced decrease in intracellular polyamine levels. Furthermore, the addition of polyamines also
reversed the ethanol-induced decrease of cell viability. These results suggest that GABA is protective against the cytotoxicity
of ethanol in isolated rat hepatocytes and this effect may be modulated by the maintenance of intracellular polyamine levels. 相似文献