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1.
2.
Haddad JJ 《Biochemical and biophysical research communications》2008,370(4):531-535
Bidirectional interdependence between the immune system and the CNS involves the intervention of common cofactors. Cytokines are endogenous to the brain, endocrine and immune systems. These shared ligands are used as a chemical language for communication. Such interaction suggests an immunoregulatory role for the brain, and a sensory function for the immune system. Interplay between the immune, nervous and endocrine systems is associated with effects of stress on immunity. Cytokines are thus capable of modulating responses in the CNS, while neuropeptides can exert their effects over cellular groups in the immune system. One way is controlled by the HPA axis, a coordinator of neuroimmune interactions that is essential to unravel in order to elucidate vital communications in a manner that this crosstalk remains a cornerstone in perpetuating a stance of homeostasis. 相似文献
3.
Summary. The accumulation of oxidized proteins is known to be linked to some severe neurodegenerative diseases like Alzheimer’s, Parkinson’s
and Huntington’s disease. Furthermore, the aging process is also accompanied by an ongoing aggregation of misfolded and damaged
proteins. Therefore, mammalian cells have developed potent degradation systems, which selectively degrade damaged and misfolded
proteins. The proteasomal system is largely responsible for the removal of oxidatively damaged proteins form the cellular
environment. Not only cytosolic proteins are prone to oxidative stress, also nuclear proteins are readily oxidized. The nuclear
proteasomal system is responsible for the degradation of these proteins. This review is focused on the specific degradation
of oxidized nuclear proteins, the role of the proteasome in this process and the regulation of the nuclear proteasomal system
under oxidative conditions. 相似文献
4.
Mühling J Nickolaus KA Matejec R Langefeld TW Harbach H Engel J Wolff M Weismüller K Fuchs M Welters ID Krüll M Heidt MC Hempelmann G 《Amino acids》2008,34(2):257-270
We examined the effects of beta-alanine (taurine analogue and taurine transport antagonist), taurine (regarding its role in neutrophil (PMN) immunonutrition) and taurine combined either with L-NAME (inhibitor of *NO-synthase), SNAP (*NO donor), DON (glutamine-analogue and inhibitor of glutamine-requiring enzymes), DFMO (inhibitor of ornithine-decarboxylase) and beta-alanine on neutrophil amino- and alpha-keto acid profiles or important PMN immune functions in order to establish whether taurine transport-, nitric oxide-, glutamine- or ornithine-dependent mechanisms are involved in any of the taurine-induced effects. According to the present findings, the taurine-mediated effect appears to be based primarily on a modulation of important transmembraneous transport mechanisms and only secondarily on directly or indirectly induced modifications in intragranulocytic amino- and alpha-keto acid homoeostasis or metabolism. Although a direct relation to the parallel observed immunological modifications can only be presumed, these results show very clearly that compositional modifications in the free intragranulocytic amino- and alpha keto-acid pools coinciding with changes in intragranulocytic taurine levels are relevant metabolic determinants that can significantly influence the magnitude and quality of the granulocytic immune response. 相似文献
5.
Several attempts at building a satisfactory model of the glucose-insulin system are recorded in the literature. The minimal
model, which is the model currently mostly used in physiological research on the metabolism of glucose, was proposed in the
early eighties for the interpretation of the glucose and insulin plasma concentrations following the intravenous glucose tolerance
test. It is composed of two parts: the first consists of two differential equations and describes the glucose plasma concentration
time-course treating insulin plasma concentration as a known forcing function; the second consists of a single equation and
describes the time course of plasma insulin concentration treating glucose plasma concentration as a known forcing function.
The two parts are to be separately estimated on the available data. In order to study glucose-insulin homeostasis as a single
dynamical system, a unified model would be desirable. To this end, the simple coupling of the original two parts of the minimal
model is not appropriate, since it can be shown that, for commonly observed combinations of parameter values, the coupled
model would not admit an equilibrium and the concentration of active insulin in the “distant” compartment would be predicted
to increase without bounds. For comparison, a simple delay-differential model is introduced, is demonstrated to be globally
asymptotically stable around a unique equilibrium point corresponding to the pre-bolus conditions, and is shown to have positive
and bounded solutions for all times. The results of fitting the delay-differential model to experimental data from ten healthy
volunteers are also shown. It is concluded that a global unified model is both theoretically desirable and practically usable,
and that any such model ought to undergo formal analysis to establish its appropriateness and to exclude conflicts with accepted
physiological notions.
Received: 22 June 1998 / Revised version: 24 February 1999 相似文献
6.
Ecological interactions between species that prefer different habitat types but come into contact in edge regions at the
interfaces between habitat types are modeled via reaction-diffusion systems. The primary sort of interaction described by
the models is competition mediated by pathogen transmission. The models are somewhat novel because the spatial domains for
the variables describing the population densities of the interacting species overlap but do not coincide. Conditions implying
coexistence of the two species or the extinction of one species are derived. The conditions involve the principal eigenvalues
of elliptic operators arising from linearizations of the model system around equilibria with only one species present. The
conditions for persistence or extinction are made explicit in terms of the parameters of the system and the geometry of the
underlying spatial domains via estimates of the principal eigenvalues. The implications of the models with respect to conservation
and refuge design are discussed.
Received: 10 June 1999 / Revised version: 7 July 2000 / Published online: 20 December 2000 相似文献
7.
Mühling J Engel J Halabi M Müller M Fuchs M Krüll M Harbach H Langefeld TW Wolff M Matejec R Welters ID Menges T Hempelmann G 《Amino acids》2006,31(1):11-26
Summary. We have examined the effects of Nω-nitro-L-arginine-methylester-hydrochloride [L-NAME; inhibitor of nitric oxide synthase], S-nitroso-N-acetyl-penicillamine
[SNAP; nitric oxide donor], α-difluoro-methyl-ornithine [DFMO; inhibitor of ornithine decarboxylase] arginine or ornithine
as well as the combination of arginine or ornithine with L-NAME, SNAP or DFMO on intracellular free amino- and α-keto acid
profiles and the immune function markers superoxide anion and hydrogen peroxide generation as well as released myeloperoxidase
activity in neutrophils (PMN). Although the underlying mechanisms still remain unclear, we believe from our results that nitric
oxide as well as polyamine-dependent pathways are involved in the signal transmission of free radical molecule, beneficial
nutritional therapy or maleficient pharmacological stress-induced alterations in PMN nutrient composition. Relevant changes
in intragranulocyte free amino- and α-keto acid homeostasis and metabolism, especially, may be one of the determinants in
PMN nutrition that positively or negatively influences and modulate neutrophil host defence capability and immunocompetence. 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.
Marchesi C Dall'Asta V Rotoli BM Bianchi MG Maggini C Gazzola GC Bussolati O 《Amino acids》2006,31(2):93-99
Summary. We report here that chlorpromazine, a first generation antipsychotic drug, inhibits anionic amino acid transport mediated
by system X−
AG (EAAT transporters) in cultured human fibroblasts. With 30 μM chlorpromazine, transport inhibition is detectable after 3 h
of treatment, maximal after 48 h (>60%), and referable to a decrease in Vmax. Chlorpromazine effect is not dependent upon changes of membrane potential and is selective for system X−
AG since transport systems A and y+ are not affected. Among antipsychotic drugs, the inhibitory effect of chlorpromazine is shared by two dibenzodiazepines,
clozapine and olanzapine, while other compounds, such as risperidon, zuclopentixol, sertindol and haloperidol, are not effective.
Transport inhibition by clozapine and olanzapine, but not by chlorpromazine, is reversible, suggesting that the mechanisms
involved are distinct. These results indicate that a subset of antipsychotic drugs inhibits EAAT transporters in non-nervous
tissues and prompt further investigation on possible alterations of glutamate transport in peripheral tissues of schizophrenic
patients. 相似文献
10.
Summary. The lancelet (amphioxus), a cephalochordate, is the closest invertebrate relative to vertebrates, with a simple vertebrate-like
body plan and a prototypical genome. We have determined D-aspartic acid (D-Asp) and major free L-amino acids (L-AAs) content
in the nervous system (neural tube) of the European amphioxus Branchiostoma lanceolatum, and have compared these values with those of molluscs and human brain. The B. lanceolatum neural tube contains relatively high amounts of L-Glu, L-Asp, L-Ala and L-Gly. Thus, the amphioxus neural tube has in common
with the molluscan and human nervous systems the presence of appreciable amounts of L-Glu and L-Asp, which suggests that they
are the most common neurotransmitters among these phylogenetically distant animal groups. The relatively high concentration
of L-Ala in amphioxus is consistent with that found in molluscs and the low concentration of taurine is consistent with that
described in the human brain.
The D-Asp concentration, very high in the molluscan nervous system, was rather low in amphioxus, although a little higher
than the extremely low amounts observed in the human brain. Our data on free amino acids composition is in agreement with
the intermediate phylogenetic position of cephalochordates, in terms of the evolutionary transition from simple to complex
neural systems. 相似文献
11.
Mühling J Burchert D Langefeld TW Matejec R Harbach H Engel J Wolff M Welters ID Fuchs M Menges T Krüll M Hempelmann G 《Amino acids》2007,33(3):511-524
Summary. We examined the effects of DON [glutamine-analogue and inhibitor of glutamine-requiring enzymes], alanyl-glutamine (regarding
its role in neutrophil immunonutrition) and alanyl-glutamine combined with L-NAME, SNAP, DON, β-alanine and DFMO on neutrophil
amino and α-keto acid concentrations or important neutrophil immune functions in order to establish whether an inhibitor of
•NO-synthase [L-NAME], an •NO donor [SNAP], an analogue of taurine and a taurine transport antagonist [β-alanine], an inhibitor
of ornithine-decarboxylase [DFMO] as well as DON could influence any of the alanyl-glutamine-induced effects. In summary,
irrespective of which pharmacological, metabolism-inhibiting or receptor-mediated mechanisms were involved, our results showed
that impairment of granulocytic glutamine uptake, modulation of intracellular glutamine metabolisation and/or de novo synthesis
as well as a blockade of important glutamine-dependent metabolic processes may led to significant modifications of physiological
and immunological functions of the affected cells. 相似文献
12.
Juan Carlos Berrío Arnoud Boom Pedro José Botero Luisa Fernanda Herrera Henry Hooghiemstra Freddy Romero Gustavo Sarmiento 《Vegetation History and Archaeobotany》2001,10(3):161-174
An environmental reconstruction of the last 10,000 14C years of a frequently flooded wetland ecosystem in the lower Magdalena valley in northern Colombia is presented, on the
basis of a multi-disciplinary study of the sediments of the upper 15 m of the core from Boquillas (74°33'E, 9°7'N; 20 m a.
s. l.). We used the following studies: pollen, lithology, organic structures, clay mineralogy, soil and sediment geochemistry,
and δ13C values. The chronology is based on 13 AMS radiocarbon dates; the humic acid fractions were used in the case of seven samples.
Pollen from local origin (swamps, open grass-rich vegetation, and gallery forest) show the development of the wetland area.
River-transported pollen from a greater distance (dry forest, montane forest, Alnus) show changes in river activity and reflect large-scale changes of climatic conditions in the Momposina basin. From c. 10,010
to 9370 uncal B. P. (zone BQS-Ia) the river system was of high energy, as inferred by the lithological changes. The landscape
was dominated by open grass-rich vegetation with gallery forest along the streams. A marked representation of Alnus and montane forest taxa indicate significant water transport and river dynamics. Climatic conditions were dry. From c. 9370-8430
uncal B. P. (zone BQS-Ib) wetlands were isolated from the main river system, and clayey sediments with kaolinite, smectite
and illite as the main minerals accumulated in a lower-energy environment. Climatic conditions were dry and changes in the
seasonal precipitation favoured the expansion of the gallery forest. From c. 8430 to 8040 uncal B. P. (zone BQS-Ic) low values
of river-transported pollen indicate dry climatic conditions and open vegetation became more abundant. The flooding frequency
of the Boquillas site diminished. From 8040 to 4900 uncal B. P. (zone BQS-Id) the Boquillas site was dominated by open vegetation
with patches of gallery forest along the streams. Supply of river-transported allochthonous pollen (from many sources) was
minimal. Clay minerals from the sediments suggest variable temperature and precipitation. From c. 4900 to 1550 uncal B. P.
)zone BQS-II) the site was within the reach of the main river system as is the case today. Frequent flooding, coinciding with
peaks of river-transported grains of Alnus and high sediment supply, point to high precipitation in the composite catchment area of the Magdalena, Cauca, San Jorge,
and Cesár rivers. High values of phosphorous in the upper part of the core point to the presence of a pre-Hispanic civilization,
approximately from 2000 uncal B. P. onward. Construction of an extensive drainage system allowed irrigation as well as drainage
depending the annual cycle of precipitation. The landscape was significantly modified and allowed an extensive crop production
on a system of raised fields.
Received May 18, 2001 / Accepted June 15, 2001 相似文献
13.
Kahana C 《Amino acids》2007,33(2):225-230
Summary. Protein degradation mediated by the ubiquitin/proteasome system is the major route for the degradation of cellular proteins.
In this pathway the ubiquitination of the target proteins is manifested via the concerted action of several enzymes. The ubiquinated
proteins are then recognized and degraded by the 26S proteasome. There are few reports of proteins degraded by the 26S protesome
without ubiquitination, with ornithine decarboxylase being the most notable representative of this group. Interestingly, while
the degradation of ODC is independent of ubiquitination, the degradation of other enzymes of the polyamine biosynthesis pathway
is ubiquitin dependent. The present review describes the degradation of enzymes and regulators of the polyamine biosynthesis
pathway. 相似文献
14.
Jang SR 《Journal of mathematical biology》2000,40(3):229-250
Several nutrient–phytoplankton–zooplankton models with internal nutrient storage by phytoplankton are derived and analyzed.
It is shown that there are thresholds beyond which the system is uniformly persistent. Variable-yield models with self-shading
of phytoplankton are also considered. With respect to uniform persistence, our result demonstrates that the global dynamics
of the system with shading are the same as those for which the self-shading mechanism is ignored.
Received: 16 March 1999 相似文献
15.
Mühling J Nickolaus KA Halabi M Fuchs M Krüll M Engel J Wolff M Matejec R Langefeld TW Welters ID Menges T Dehne MG Sablotzki A Hempelmann G 《Amino acids》2005,29(3):289-300
Summary. The objective of this study was to determine the dose as well as duration of exposure-dependent effects of L-alanyl-L-glutamine,
arginine or taurine on polymorphonuclear neutrophil (PMN) free α-keto acid profiles and, in a parallel study, on PMN immune
functions. Exogenous L-alanyl-L-glutamine significantly increased PMN α-ketoglutarate, pyruvate PMN superoxide anion (O2−) generation, hydrogen peroxide (H2O2) formation and released myeloperoxidase (MPO) activity. Arginine also led to significant increases in α-ketoglutarate, pyruvate,
MPO release and H2O2 generation. Formation of O2− on the other hand was decreased by arginine. Incubation with taurine resulted in lower intracellular pyruvate and α-ketobutyrate
levels, decreased O2− and H2O2 formation and a concomitant significantly increased MPO activity. We therefore believe that considerable changes in PMN free-α-keto-acid
profiles, induced for example by L-alanyl-L-glutamine, arginine or taurine, may be one of the determinants in cell nutrition
that considerably modulates the immunological competence of PMN. 相似文献
16.
Brandsch M 《Amino acids》2006,31(2):119-136
Summary. Membrane transport of L-proline has received considerable attention in basic and pharmaceutical research recently. Of the
most recently cloned members of the solute carrier family, two are “proline transporters”. The amino acid transporter PAT1,
expressed in intestine, kidney, brain and other organs, mediates the uptake of proline and derivatives in a pH gradient-dependent
manner. The Na+-dependent proline transporter SIT1, cloned in 2005, exhibits the properties of the long-sought classical IMINO system. Proline-containing
peptides are of interest for several reasons. Many biologically important peptide sequences contain highly conserved proline
residues. Xaa-Pro peptides are very often resistant to enzymatic hydrolysis and display, in contrast to Pro-Xaa peptides,
a high affinity to the H+/peptide cotransporter PEPT1 which is expressed in intestinal, renal, lung and biliary duct epithelial cells. Furthermore,
several orally available drugs are recognized by PEPT1 as Xaa-Pro analogues due to their sterical resemblance to small peptides. 相似文献
17.
18.
Summary. It has been firmly established that excitatory amino acids (EAAs), such as glutamate, are pivotal elements in the hypothalamic
circuitry involved in the control of pituitary function. The actions of EAAs are mediated by different postsynaptic receptor
subtypes, which include N-methyl D-aspartate (NMDA), kainate (KA), 2-amino-3-hydroxy-5 methyl-4-isoxazol propionic acid (AMPA)
and metabotropic receptors. In this review, we summarize our experimental work on the role of EAA neurotransmission in the
control of GH secretion in the rat. Detailed characterization of the effects of agonists and antagonists of glutamate receptors
on GH release revealed that activation of NMDA, KA and AMPA receptors at different age-points resulted in clear-cut stimulation
of GH secretion, although age- and sex-dependent differences were detected in the pattern of response to the different agonists.
This stimulatory action was proven nitric oxide (NO)-dependent and not exerted at the pituitary level. In addition, evaluation
of the role of hypothalamic GH-releasing hormone (GHRH) in the stimulatory action of NMDA by means of immunoneutralization
of endogenous GHRH or destruction of GHRH producing neurons suggested the involvement of signals other than GHRH in this response.
Further, evidence was obtained on the modulation of the EAA system by gonadal factors, and on the physiological relevance
of EAA pathways in the regulation of pulsatile GH release. In conclusion, our data using the rat as animal model provide evidence
for a pivotal role of glutamate pathways in the regulation of GH secretion throughout the life-span.
Received May 5, 1999, Accepted July 28, 1999 相似文献
19.
Sahún I Gallego X Gratacòs M Murtra P Trullás R Maldonado R Estivill X Dierssen M 《Amino acids》2007,33(4):677-688
Summary. Sensitivity to pharmacological challenges has been reported in patients with panic disorder. We have previously validated
transgenic mice overexpressing the neurotrophin-3 (NT-3) receptor, TrkC (TgNTRK3), as an engineered murine model of panic
disorder. We could determine that TgNTRK3 mice presented increased cellularity in brain regions, such as the locus ceruleus,
that are important neural substrates for the expression of anxiety in severe anxiety states. Here, we investigated the sensitivity
to induce anxiety and panic-related symptoms by sodium lactate and the effects of various drugs (the α2-adrenoceptor antagonist,
yohimbine and the adenosine antagonist, caffeine), in TgNTRK3 mice. We found enhanced panicogenic sensitivity to sodium lactate
and an increased intensity and a differential pattern of Fos expression after the administration of yohimbine or caffeine
in TgNTRK3. Our findings validate the relevance of the NT-3/TrkC system to pathological anxiety and raise the possibility
that a specific set of fear-related pathways involved in the processing of anxiety-related information may be differentially
activated in panic disorder. 相似文献
20.
Summary. Gliotransmission is a process in which astrocytes are dynamic elements that influence synaptic transmission and synaptogenesis.
The best-known gliotransmitters are glutamate and ATP. However, in the past decade, it has been demonstrated that D-serine,
a D-amino acid, acts as a gliotransmitter in glutamatergic synapses. The physiological relevance of D-serine is sustained
by the way in which it modulates the action of glutamatergic neurotransmission, neuronal migration and long-term potentiation
(LTP). In addition, the synthesis and degradation mechanisms of D-serine have been proposed as potential therapeutic targets
for the treatment of Alzheimer’s disease, schizophrenia and related disorders. In the present review, detailed information
is provided about the physiological and physiopathological relevance of D-serine, including metabolic and regulation aspects. 相似文献