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1.
Increase in putrescine,amine oxidase,and acrolein in plasma of renal failure patients 总被引:1,自引:0,他引:1
Sakata K Kashiwagi K Sharmin S Ueda S Irie Y Murotani N Igarashi K 《Biochemical and biophysical research communications》2003,305(1):143-149
Since polyamines have been suggested to be one of the uremic "toxins," the levels of each polyamine, its oxidized product, acrolein, and amine oxidase in plasma of patients with renal failure were investigated. The level of putrescine was increased, whereas the level of spermine was decreased in the plasma of patients with renal failure. The patients also had increased serum amine oxidase activity leading to increased degradation of spermine. Both levels of free and protein-conjugated acrolein were also increased in plasma of patients with renal failure. The accumulated acrolein found as protein conjugates was equivalent to 180 microM, which was 6-fold higher than in plasma of normal subjects. It was found that acrolein is mainly produced by polyamine oxidase in plasma. A cell lysate containing polyamine oxidase was cytotoxic in the presence of spermine. Our results indicate that the level of acrolein is well correlated with the degree of seriousness of chronic renal failure. 相似文献
2.
Nikolic J Stojanovic I Pavlovic R Sokolovic D Bjelakovic G Beninati S 《Amino acids》2007,32(1):127-131
Summary. The existing interrelation in metabolic pathways of L-arginine to polyamines, nitric oxide (NO) and urea synthesis could be
affected in sepsis, inflammation, intoxication and other conditions. The role of polyamines and NO in the toxic effect of
mercury chloride on rat liver function was studied. Administration of mercury chloride for 24 h led to significantly elevated
plasma activities of Alanine transaminase (ALT) and Aspartate transaminase (AST). Malondyaldehyde (MDA) levels were unaffected
(p > 0.05) and arginase activity was significantly decreased (p < 0.05) while nitrate/nitrite production was significantly
elevated (p < 0.001) in liver tissue. Polyamine oxidase (PAO) and diamine oxidase (DAO) activities, enzymes involved in catabolism
of polyamines, were decreased. L-arginine supplementation to intoxicated rats potentiated the effect of mercury chloride on
NO production and it was ineffective on arginase activity.
Results obtained in this study show that mercury chloride-induced toxicity leads to abnormally high levels of ALT and AST
that may indicate liver damage with the involvement of polyamine catabolic enzymes and NO. 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.
Bjelaković G Beninati S Pavlović D Sokolović D Stojanović I Jevtović T Bjelaković GB Nikolić J Basić J 《Amino acids》2007,33(3):525-529
Summary. Our study was undertaken to elucidate the effects of selenomethionine (SeMet) on polyamine metabolism in regenerating rat
liver tissue, as useful model of rapidly growing normal tissue. We have examined the levels of spermine, spermidine and putrescine
in liver tissue. At the same time we have evaluated the activities of polyamine oxidase (PAO) and diamine oxidase (DAO), the
catabolic enzymes of polyamine metabolism.
The obtained results suggest that polyamine levels in regenerating liver tissue, at 7th day after two-thirds partial hepatectomy, were higher in comparison with control group. The administration of selenomethionine
to hepatectomized animals during seven days, in a single daily dose of 2.5 μg/100 g body weight, increases the amount of spermine
and spermidine; the level of putrescine does not change under the influence of SeMet in regenerating rat liver tissue.
PAO activity is lower in regenerating hepatic tissue than in control group. Supplementation of hepatectomized animals with
SeMet significantly decreases the activity of this enzyme. DAO activity was significantly higher in hepatectomized and in
operated animals treated with SeMet compared to the sham-operated and control ones.
The differential sensitivity observed in our model of highly proliferating normal tissue to SeMet, compared with the reported
anticancer activity of this molecule is discussed. 相似文献
5.
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
6.
Summary. Due to the similarity in transport characteristics of polyamines and the y+ basic amino acid system, we hypothesized that both substrates could be moving through a common carrier site. Competitive
and cross inhibition experiments in intestinal epithelial cells revealed the possibility of a common transport site. N-ethylmalemide
(NEM) inhibited both lysine and putrescine transport, confirming that both were carried by a y+ transporter. Overexpressing the y+ transporter CAT-1 in a polyamine transport-deficient cell line, CHO-MG, did not reconstitute polyamine-transport. Thus, polyamines
are not traveling through CAT-1. To determine if lysine is carried by a polyamine transport site, an antizyme-overexpressing
cell line was used. Antizyme overexpression decreased polyamine uptake by 50%; in contrast, lysine transport was unaffected.
Therefore, lysine is not traveling through a polyamine transport site. It appears that polyamines and lysine are likely traveling
through a common unknown y+ transport site. 相似文献
7.
Summary. The polyamines are growth factors in both normal and cancer cells. As the intracellular polyamine content correlates positively
with the growth potential of that cell, the idea that depletion of polyamine content will result in inhibition of cell growth
and, particularly tumour cell growth, has been developed over the last 15 years. The polyamine pathway is therefore a target
for development of rationally designed, antiproliferative agents. Following the lessons from the single enzyme inhibitors
(α-difluoromethylornithine DFMO), three generations of polyamine analogues have been synthesised and tested in vitro and in vivo. The analogues are multi-site inhibitors affecting multiple reactions in the pathway and thus prevent the up-regulation of
compensatory reactions that have been the downfall of DFMO in anticancer chemotherapy. Although the initial concept was that
the analogues may provide novel anticancer drugs, it now seems likely that the analogues will have wider applications in diseases
involving hyperplasia. 相似文献
8.
Summary. Polyamines and the metabolic and physiopathological processes in which they are involved represent an active field of research
that has been continuously growing since the seventies. In the last years, the trends in the focused areas of interest within
this field since the 1970s have been confirmed. The impact of “-omics” in polyamine research remains too low in comparison
with its deep impact on other biological research areas. These high-throughput approaches, along with systems biology and,
in general, more systemic and holistic approaches should contribute to a renewal of this research area in the near future. 相似文献
9.
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
10.
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
11.
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
12.
Consequences of renal mass reduction on amino acid and biogenic amine levels in nephrectomized mice 总被引:2,自引:0,他引:2
Summary. Amino acid and biogenic amine changes were investigated in nephrectomized mice ten days postsurgery. Uremic mice exhibited
changes in amino acid concentrations in plasma, urine and brain. Particularly plasma methionine, citrulline and arginine levels
were significantly enhanced in nephrectomized mice compared to controls whereas serine was decreased. Urinary excretion of
methionine, citrulline and alanine was higher in nephrectomized mice compared to controls whereas many amino acids were increased
in brain of nephrectomized mice. Brain and urinary amino acid changes were more pronounced in the 75% than in the 50% nephrectomized
mice. Brain norepinephrine and dopamine and its metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid were significantly
increased whereas serotonin was decreased comparing the 75% nephrectomized mice to the sham-operated mice. This study demonstrates
that at very early stages of renal insufficiency, specific amino acid and biogenic amine changes occur in plasma, urine and
brain. These alterations might depend qualitatively and quantitatively on the degree of functional renal mass reduction.
Received April 5, 1999 相似文献
13.
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
14.
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
15.
Rectification of the Olfactory Cyclic Nucleotide-Gated Channel by Intracellular Polyamines 总被引:5,自引:0,他引:5
J.W. Lynch 《The Journal of membrane biology》1999,170(3):213-227
Polyamine-induced inward rectification of cyclic nucleotide-gated channels was studied in inside-out patches from rat olfactory
neurons. The polyamines, spermine, spermidine and putrescine, induced an `instantaneous' voltage-dependent inhibition with
K
d
values at 0 mV of 39, 121 μm and 2.7 mm, respectively. Hill coefficients for inhibition were significantly < 1, suggesting an allosteric inhibitory mechanism. The
Woodhull model for voltage-dependent block predicted that all 3 polyamines bound to a site 1/3 of the electrical distance
through the membrane from the internal side. Instantaneous inhibition was relieved at positive potentials, implying significant
polyamine permeation. Spermine also induced exponential current relaxations to a `steady-state' impermeant level. This inhibition
was also mediated by a binding site 1/3 of the electrical distance through the pore, but with a K
d
of 2.6 mm. Spermine inhibition was explained by postulating two spermine binding sites at a similar depth. Occupation of the first
site occurs rapidly and with high affinity, but once a spermine molecule has bound, it inhibits spermine occupation of the
second binding site via electrostatic repulsion. This repulsion is overcome at higher membrane potentials, but results in
a lower apparent binding affinity for the second spermine molecule. The on-rate constant for the second spermine binding saturated
at a low rate (∼200 sec−1 at +120 mV), providing further evidence for an allosteric mechanism. Polyamine-induced inward rectification was significant
at physiological concentrations.
Received: 17 February 1999/Revised: 27 April 1999 相似文献
16.
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
17.
Marcocci L Casadei M Faso C Antoccia A Stano P Leone S Mondovì B Federico R Tavladoraki P 《Amino acids》2008,34(3):403-412
Summary. In this study, polyamine oxidase from maize (MPAO), which is involved in the terminal catabolism of spermidine and spermine
to produce an aminoaldehyde, 1,3-diaminopropane and H2O2, has been conditionally expressed at high levels in the nucleus of MCF-7 human breast cancer cells, with the aim to interfere
with polyamine homeostasis and cell proliferation. Recombinant MPAO expression induced accumulation of a high amount of 1,3-diaminopropane,
an increase of putrescine levels and no alteration in the cellular content of spermine and spermidine. Furthermore, recombinant
MPAO expression did not interfere with cell growth of MCF-7 cells under normal conditions but it did confer higher growth
sensitivity to etoposide, a DNA topoisomerase II inhibitor widely used as antineoplastic drug. These data suggest polyamine
oxidases as a potential tool to improve the efficiency of antiproliferative agents despite the difficulty to interfere with
cellular homeostasis of spermine and spermidine.
Authors’ address: Dr. Paraskevi Tavladoraki, Department of Biology, University ‘Roma Tre’, Viale G. Marconi 446, 00146 Rome,
Italy 相似文献
18.
Summary. In the kidney the proximal tubule is responsible for the uptake of amino acids. This occurs via a variety of functionally
and structurally different amino acid transporters located in the luminal and basolateral membrane. Some of these transporters
show an ion-dependence (e.g. Na+, Cl− and K+) or use an H+-gradient to drive transport. Only a few amino acid transporters have been cloned or functionally characterized in detail
so far and their structure is known, while little is known about a majority of amino acid transporters. Only few attempts
have been untertaken looking at the regulation of amino acid transport. We summarized more recent information on amino acid
transport in the renal proximal tubule emphasizing functional and regulatory aspects.
Received August 8, 1999; Accepted April 20, 2000 相似文献
19.
Summary. Background: Asymmetrical dimethylarginine (ADMA) is an inhibitor of nitric-oxide synthase. It has been linked to atherosclerotic risk
in the general population as well as in end-stage renal disease patients (ESRD), whereas symmetrical dimethylarginine (SDMA)
is thought to be biological inactive. Prospective data concerning the role of both dimethylarginines are rare in patients
with chronic kidney disease.
Methods: 200 patients with chronic kidney disease (mean age 57.6 ± 13.0 years, 69 female, 131 male); 82 with chronic renal failure
(CRF), 81 on maintenance haemodialysis (HD) and 37 renal transplant recipients (RTR) were prospectively followed for 24 months.
ADMA and SDMA were measured by HPLC. The relation of plasma levels of ADMA and SDMA together with conventional risk factors
for the cardiovascular and renal outcome was investigated with Cox proportional hazards model.
Results: Mean serum levels of SDMA were significantly increased in all groups compared to the control group (P ≤ 0.0005), ADMA was increased only in HD and RTR (P ≤ 0.004). Forty-seven cardiovascular events (CVE) occurred during follow-up, 35 patients died, and 39 patients reached ESRD.
Multivariate analysis showed diabetes (RR 3.072, P = 0.01), ESRD (RR 11.915, P < 0.0005), elevated CRP levels (RR 3.916, P < 0.0005) and surprisingly a lower ADMA level (RR 0.271, P = 0.008) as independent risk factors for CVE. Serum creatinine (RR 11.378, P = 0.001), haemoglobin (RR 0.710, P = 0.038 for an increment of 1 mmol/l), and SDMA levels (RR 1.633, P = 0.006, per 1 μmol/l increment) were predictors for the progression to ESRD.
Conclusions: Data from a heterogeneous group of patients with chronic kidney disease provide evidence that conventional risk factors
seem to play a more important role than elevated serum levels of ADMA or SDMA for cardiovascular events. Increasing serum
SDMA concentration seems to play an additive role for the renal outcome besides serum creatinine and haemoglobin levels. Whether
ADMA might possibly be a candidate for the phenomenon of “paradoxical epidemiology” in chronic kidney disease needs further
investigation. 相似文献
20.
Summary. Polyamines, in particular spermine, as well as some natural and synthetic polyamine derivatives have been found to be blockers
of N-methyl-d-aspartate receptors. We developed novel, polyamine-based channel blockers to analyze the structure of NMDA receptors. Anthraquinone
polyamines block NMDA receptors with some selectivity compared to other glutamate receptors. Results using mutant NR1 and
NR2 subunits identified amino acid residues that influence blockade by anthraquinone polyamines. The head group (anthraquinone)
may be positioned at the selectivity filter/narrowest constriction of the channel and the polyamine tail penetrates this constriction
into the inner vestibule below the level of the selectivity filter. The results are consistent with other work showing that
NR1 (Asn616) and NR2B (Asn616), but not NR2B (Asn615), make the narrowest constriction of NMDA channel, and that the M3 segments
from the two subunits, which form the outer vestibule, are likely staggered relative to each other in the vertical axis of
the channel. 相似文献