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1.
The oxidative stress-inducible cystine/glutamate exchange system, system xc−, transports one molecule of cystine, the oxidized form of cysteine, into cells and thereby releases one molecule of glutamate
into the extracellular space. It consists of two protein components, the 4F2 heavy chain, necessary for membrane location
of the heterodimer, and the xCT protein, responsible for transport activity. Previously, system xc− has been regarded to be a mere supplier of cysteine to cells for the synthesis of proteins and the antioxidant glutathione
(GSH). In that sense, oxygen, electrophilic agents, and bacterial lipopolysaccharide trigger xCT expression to accommodate
with increased oxidative stress by stimulating GSH biosynthesis. However, emerging evidence established that system xc− may act on its own as a GSH-independent redox system by sustaining a redox cycle over the plasma membrane. Hallmarks of this
cycle are cystine uptake, intracellular reduction to cysteine and secretion of the surplus of cysteine into the extracellular
space. Consequently, increased levels of extracellular cysteine provide a reducing microenvironment required for proper cell
signaling and communication, e.g. as already shown for the mechanism of T cell activation. By contrast, the enhanced release
of glutamate in exchange with cystine may trigger neurodegeneration due to glutamate-induced cytotoxic processes. This review
aims to provide a comprehensive picture from the early days of system xc− research up to now. 相似文献
2.
The cystine/glutamate exchanger (antiporter xc−) is a membrane transporter involved in the uptake of cystine, the rate-limiting amino acid in the synthesis of glutathione.
Recent studies suggest that the antiporter plays a role in the slow oxidative excitotoxity and in the pathological effects
of β-N-oxalylamino-l-alanine, the molecule responsible for neurolathyrism, a neurotoxic upper motor neuron disease. The mouse cystine/glutamate
exchanger has been cloned and showed to be composed of two distinct proteins, one of which being a novel protein, named xCT,
of 502 amino acids and 12 putative trans-membrane domains. We have generated and purified a polyclonal antibody to mouse xCT
and studied its expression in rat brain and in different cultured cells (astrocytes, fibroblasts and neurons) using Western
blot and immunocytochemical techniques. Expression of xCT was also studied in rat brain and muscle at different developmental
stages. Parallel experiments were carried out with antibodies to the heavy chain of 4F2 surface antigen, the non-specific
subunit of the antiporter xc−. xCT antibody detected in all cell and tissue extracts a specific band of about 40 kDa. Subcellular fractionation demonstrated
that xCT is concentrated mainly in the microsomal-mitochondrial fraction, in accord with its structure as transmembrane protein.
Immunocytochemical analysis showed a strong staining in all cells examined, included neurons. Furthermore, both xCT and the
heavy chain of 4F2 surface antigen increased in the brain during development, reaching the highest expression in adulthood.
The study of the expression and developmental profile of xCT represents a first step towards a better characterization of
its biochemical properties and function, which in turn may help to understand the relative contribution of the xc− antiporter in the pathogenesis of certain neurodegenerative diseases. 相似文献
3.
Dun Y Mysona B Van Ells T Amarnath L Ola MS Ganapathy V Smith SB 《Cell and tissue research》2006,324(2):189-202
The cystine-glutamate exchanger, system xc
−, mediates the Na+-independent exchange of cystine into cells, coupled to the efflux of intracellular glutamate. System xc
− plays a critical role in glutathione homeostasis. Early studies of brain suggested that system xc
− was present primarily in astrocytes but not neurons. More recent work indicates that certain brain neurons have an active system xc
−. In the retina, system xc
− has been demonstrated in Müller and retinal pigment epithelial cells. We have recently suggested that two protein components of system xc
−, xCT and 4F2hc, are present in ganglion cells of the intact retina. Here, we have used (1) molecular and immunohistochemical assays to determine whether system xc
− is present in primary ganglion cells isolated from neonatal mouse retinas and (2) functional assays to determine whether its activity is regulated by oxidative stress in a retinal ganglion cell line (RGC–5). Primary mouse ganglion cells and RGC–5 cells express xCT and 4F2hc. RGC–5 cells take up [3H]glutamate in the absence of Na+, and this uptake is blocked by known substrates of system xc
− (glutamate, cysteine, cystine, quisqualic acid). Treatment of RGC–5 cells with NO and reactive oxygen species donors leads to increased activity of system xc
− associated with an increase in the maximal velocity of the transporter with no significant change in the substrate affinity. This is the first report of system xc
− in primary retinal ganglion cells and RGC–5 cells. Oxidative stress upregulates this transport system in RGC–5 cells, and the process is associated with an increase in xCT mRNA and protein but no change in 4F2hc mRNA or protein. This work was supported by National Institutes of Health grants EY014560 and EY012830. 相似文献
4.
Glutathione (γ-glutamylcysteinylglycine, GSH and oxidized glutathione, GSSG), may function as a neuromodulator at the glutamate
receptors and as a neurotransmitter at its own receptors. We studied now the effects of GSH, GSSG, glutathione derivatives
and thiol redox agents on the spontaneous, K+- and glutamate-agonist-evoked releases of [3H]dopamine from mouse striatal slices. The release evoked by 25 mM K+ was inhibited by GSH, S-ethyl-, -propyl-, -butyl- and pentylglutathione and glutathione sulfonate. 5,5′-Dithio-bis-2-nitrobenzoate (DTNB) and l-cystine were also inhibitory, while dithiothreitol (DTT) and l-cysteine enhanced the K+-evoked release. Ten min preperfusion with 50 μM ZnCl2 enhanced the basal unstimulated release but prevented the activation of K+-evoked release by DTT.
Kainate and 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) evoked dopamine release but the other glutamate receptor
agonists N-methyl-d-aspartate (NMDA), glycine (1 mM) and trans-1-aminocyclopentane-1,3-dicarboxylate (t-ACPD, 0.5 mM), and the modulators GSH, GSSG, glutathione sulfonate, S-alkyl-derivatives of glutathione, DTNB, cystine, cysteine and DTT (all 1 mM) were without effect. The release evoked by 1 mM
glutamate was enhanced by 1 mM GSH, while GSSG, glutathionesulfonate and S-alkyl derivatives of glutathione were generally without effect or inhibitory. NMDA (1 mM) evoked release only in the presence
of 1 mM GSH but not with GSSG, other peptides or thiol modulators. l-Cysteine (1 mM) enhanced the glutamate-evoked release similarly to GSH. The activation by 1 mM kainate was inhibited by S-ethyl-, -propyl-, and -butylglutathione and the activation by 0.5 mM AMPA was inhibited by S-ethylglutathione but enhanced by GSSG.
Glutathione alone does not directly evoke dopamine release but may inhibit the depolarization-evoked release by preventing
the toxic effects of high glutamate, and by modulating the cysteine–cystine redox state in Ca2+ channels. GSH also seems to enhance the glutamate-agonist-evoked release via both non-NMDA and NMDA receptors. In this action,
the γ-glutamyl and cysteinyl moieties of glutathione are involved. 相似文献
5.
Sephashvili M Zhuravliova E Barbakadze T Khundadze M Narmania N Mikeladze DG 《Neurochemical research》2006,31(10):1205-1210
Homocysteine is a sulfur-containing, nonproteinogenic, neurotoxic amino acid biosynthesized during methyl cycles after demethylation of S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH) and subsequent hydrolysis of SAH into homocysteine and adenosine. Formed homocysteine is either catabolized into cystathionine (transsulfuration pathway) by cystathionine β-synthase, or remethylated into methionine (remethylation pathway) by methionine synthase. To demonstrate the specificity of Ras-elicited effects on the activity of methyl cycles, wild-type pheochromocytoma PC12, mutant oncogenic rasH gene (MVR) expressing PC12 pheochromocytoma and normal c-rasH stably transfected M-CR3B cells were incubated with the Nω-nitro-l-arginine methyl ester (l-NAME), and manumycin, (inhibitors of nitric oxide synthase and farnesyltransferase, respectively). We have found that l-NAME significantly changes the SAM/SAH ratio in both MCR and MVR cells. Moreover, these alterations have reciprocal character; in the MCR cells, the SAM/SAH ratio was raised, whereas in the MVR cells this ratio was decreased. We conclude that depletion of endogenous NO with l-NAME increased the production of SAH only in cells with mutated oncogenic RasH, possibly through enhancement of production of reactive oxygen species (ROS). Oxidative stress can increase cystathionine β-synthase activity that switches methyl cycles from remethylation into transsulfuration pathway to maintain the intracellular glutathione pool (essential for the redox-regulating capacity of cells) via an adaptive process. 相似文献
6.
Uptake of glyeine,l-cysteine,l-leucine,l-methionine,l-aspartic acid andl-lysine was investigated in resting cells ofSaccharomyces cerevisiae treated with 0.3mm actidione for blocking protein synthesis. The amino acids were taken up against substantial concentration gradients (up to
nearly 1,000∶1 for μm l-cysteine and glycine). They were present in the free form inside the cells. Their unidirectional transmembrane fluxes were
under a negative feedback control by the intracellular concentration of the amino acid involved. The amino acids tested apparently
employed more than one transport agéncies for their membrane passage, the half-saturation constants being 6.2–7.7×10−4
m for glycine, 2.5×10−4
m forl-cysteine, 6×10−5 and 4×10−4
m forl-lysine, 3×10−5 and 6×10−4
m forl-methionine, 7–18×10−5 and 1.6×10−3
m forl-aspartic acid and 6×10−5 and 2×10−3
m forl-leucine. The specificities of the transport systems are overlapping but there emerges a wide-affinity transport system for
glycine, alanine, leucine, methionine, serine, cysteine, phenylalanine, aspartic acid, asparagine, glutamic acid and tryptophan
(and possibly for other amino acids), and more specific systems for each of the following: glycine, lysine, methionine, histidine,
arginine, and aspartic and glutamic acids. Proline had the peculiar effect of stimulating the transport of all the amino acids
tested. The amino acids apparently interacted in the uptake not only by competition for the binding site but also by allotopic
inhibition (e.g.l-cysteine) and possibly stimulation (l-proline). The initial rate of uptake of amino acids and their steady-state level of distribution were characterized by identical
activation energies: 7.5 kcal/mole forl-lysine, 6.9 kcal/mole forl-aspartic acid, and 13.2 kcal/mole for glycine. 相似文献
7.
Takashi Nemoto Taisuke Watanabe Yutaka Mizogami Jun-ichi Maruyama Katsuhiko Kitamoto 《Applied microbiology and biotechnology》2009,82(6):1105-1114
The recombinant Pichia pastoris harboring an improved methionine adenosyltransferase (MAT) shuffled gene was employed to biosynthesize S-adenosyl-l-methionine (SAM). Two l-methionine (l-Met) addition strategies were used to supply the precursor: the batch addition strategy (l-Met was added separately at three time points) and the continuous feeding strategies (l-Met was fed continuously at the rate of 0.1, 0.2, and 0.5 g l−1 h−1, respectively). SAM accumulation, l-Met conversion rate, and SAM productivity with the continuous feeding strategies were all improved over the batch addition
strategy, which reached 8.46 ± 0.31 g l−1, 41.7 ± 1.4%, and 0.18 ± 0.01 g l−1 h−1 with the best continuous feeding strategy (0.2 g l−1 h−1), respectively. The bottleneck for SAM production with the low l-Met feeding rate (0.1 g L−1 h−1) was the insufficient l-Met supply. The analysis of the key enzyme activities indicated that the tricarboxylic acid cycle and glycolytic pathway
were reduced with the increasing l-Met feeding rate, which decreased the adenosine triphosphate (ATP) synthesis. The MAT activity also decreased as the l-Met feeding rate rose. The reduced ATP synthesis and MAT activity were probably the reason for the low SAM accumulation when
the l-Met feeding rate reached 0.5 g l−1 h−1. 相似文献
8.
S. Schöniger T. Caprile C. R. Yulis Q. Zhang E. M. Rodríguez F. Nürnberger 《Cell and tissue research》2009,336(3):477-488
Elevated glutamate levels have been reported in humans with diabetic retinopathy. Retinal Müller glial cells regulate glutamate
levels via the GLAST transporter and system xc
− (cystine-glutamate exchanger). We have investigated whether transporter function and gene and/or protein expression are altered
in mouse Müller cells cultured under conditions of hyperglycemia or oxidative stress (two factors implicated in diabetic retinopathy).
Cells were subjected to hyperglycemic conditions (35 mM glucose) over an 8-day period or to oxidative stress conditions (induced
by exposure to various concentrations of xanthine:xanthine oxidase) for 6 h. The Na+-dependent and –independent uptake of [3H] glutamate was assessed as a measure of GLAST and system xc
− function, respectively. Hyperglycemia did not alter the uptake of [3H] glutamate by GLAST or system xc
−; neither gene nor protein expression decreased. Oxidative stress (70:14 or 100:20 μM xanthine:mU/ml xanthine oxidase) decreased
GLAST activity by ~10% but increased system xc
− activity by 43% and 89%, respectively. Kinetic analysis showed an oxidative-stress-induced change in Vmax, but not Km. Oxidative stress caused a 2.4-fold increase in mRNA encoding xCT, the unique component of system xc
−. Of the two isoforms of xCT (40 and 50 kDa), oxidative stress induced a 3.6-fold increase in the 40-kDa form localized to
the plasma membrane. This is the first report of the differential expression and localization of xCT isoforms as caused by
cellular stress. Increased system xc
− activity in Müller cells subjected to conditions associated with diabetic retinopathy may be beneficial, as this exchanger
is important for the synthesis of the antioxidant glutathione.
This work was supported by NIH R01 EY014560. 相似文献
9.
Nadine Summa Tanja Soldatovi Lutz Dahlenburg ivadin D. Bugari Rudi van Eldik 《Journal of biological inorganic chemistry》2007,12(4):461-475
A set of three oxaliplatin derivatives containing 1,2-trans-R,R-diaminocyclohexane (dach) as a spectator ligand and different chelating leaving groups X–Y, viz., [Pt(dach)(O,O-cyclobutane-1,1-dicarboxylate)], or Pt(dach)(CBDCA), [Pt(dach)(N,O-glycine)]+, or Pt(dach)(gly), and [Pt(dach)(N,S-methionine)]+, or Pt(dach)(l-Met), where l-Met is l-methionine, were synthesized and the crystal structure of Pt(dach)(gly) was determined by X-ray diffraction. The effect of
the leaving group on the reactivity of the resulting Pt(II) complexes was studied for the nucleophiles thiourea, glutathione
(GSH) and l-Met under pseudo-first-order conditions as a function of nucleophile concentration and temperature, using UV–vis spectrophotometric
techniques. 1H NMR spectroscopy was used to follow the substitution of the leaving group by guanosine 5′-monophosphate (5′-GMP2−) under second-order conditions. The rate constants indicate for all reactions a direct substitution of the X–Y chelate by
the selected nucleophiles, thereby showing that the nature of the chelate, viz., O–O (CBDCA2−), N–O (glycine) or S–N (l-Met), respectively, plays an important role in the kinetic and mechanistic behavior of the Pt(II) complex. The k
1 values for the reaction with thiourea, l-Met, GSH and 5′-GMP2− were found to be as follows (103
k
1, 37.5 °C, M−1 s−1): Pt(dach)(CBDCA) 61 ± 2, 21.6 ± 0.1, 23 ± 1, 0.352 ± 0.002; Pt(dach)(gly) 82 ± 3, 6.2 ± 0.2, 37 ± 1, 1.77 ± 0.01; Pt(dach)(l-Met) (thiourea, GSH) 62 ± 2, 24 ± 1. The activation parameters for all reactions studied suggest an associative substitution
mechanism.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
10.
We earlier found that seleno-l-methionine (L-SeMet) as a food source of selenium (Se) is directly converted to methylselenol (CH3SeH), α-ketobutyrate, and ammonia by the mouse hepatic cystathionine γ-lyase. The purpose of this study was to clarify the
biological role of cystathionine γ-lyase in Se detoxification and cytosolic glutathione peroxidase (cGPx) biosynthesis because
another metabolic pathway to CH3SeH via seleno-l-cystathionine and seleno-l-cysteine (l-SeCyH) from l-SeMet has been shown by several enzymatic reactions. When mice were treated with either toxic doses of l-SeMet or a Se-deficient diet, the cystathionine γ-lyase activity for l-SeMet was invariable, suggesting that this enzyme was effective in both detoxification and biotransformation of Se. Concerning
Se biotransformation into cGPx, production of H2Se as the possible precursor was not observed by the in vitro reaction of the liver cytosol with CH3SeH. When l-SeMet was administered at the nutritional dose to mice fed a Se-deficient diet, levels of both cGPx mRNA and cGPx protein
were significantly restored. This recovery was not comparatively suppressed by coadministration of periodate-oxidized adenosine,
an inhibitor of S-adenosylhomo-cystenase, where the conversion of l-SeMet to l-SeCyH is inhibited. However, the recovery was strongly suppressed when propargylglycine, an inhibitor of cystathioine γ-lyase
that catalyzes the α,γ-elimination reaction of both l-SeMet and seleno-l-cystathionine, was treated. These results suggest that cystathionine γ-lyase is a notable enzyme, in SeMet metabolism and
that CH3SeH produced by the enzymatic reaction is utilized for cGPx biosynthesis. 相似文献
11.
This study showed that sclerotial differentiation in the filamentous phytopathogenic fungus Rhizoctonia solani is directly related to oxidative stress and thiol redox state (TRS). Sclerotial differentiation is modulated by the availability
of non-cytotoxic −SH groups as was shown by the inhibition of sclerorial differentiation by the TRS modulator N-acetyl cysteine
(AcCSH), and not necessarily with those of the TRS reduced components glutathione (GSH) and its precursor cysteine (CSH) as
indicated by the GSH-biosynthesis inducer and inhibitor l-2–oxo-thiazolidine-4-carboxylate and l-buthionine-S,R-sulfoximine, respectively. Moreover, inhibition of sclerotial differentiation was accompanied by decrease
of the high oxidative stress indicators, lipid peroxidation and DNA damage in the mycelial substrate where sclerotia initials
are formed, which suggests that this phenomenon is related to oxidative stress as it is predicted by our theory on sclerotial
differentiation. 相似文献
12.
Toyin Adeyemi Ogunrinu Harald Sontheimer 《The Journal of biological chemistry》2010,285(48):37716-37724
Glutathione (GSH) is an essential antioxidant responsible for the maintenance of intracellular redox homeostasis. As tumors outgrow their blood supply and become hypoxic, their redox homeostasis is challenged by the production of nitric oxide and reactive oxygen species (ROS). In gliomas, the sustained import of l-cystine via the l-cystine/l-glutamate exchanger, system xc−, is rate-limiting for the synthesis of GSH. We show that hypoxia causes a significant increase in NO and ROS but without affecting glioma cell growth. This is explained by a concomitant increase in the utilization of GSH, which is accompanied by an increase in the cell-surface expression of xCT, the catalytic subunit of system xc−, and l-cystine uptake. Growth was inhibited when GSH synthesis was blocked by buthionine sulfoximine (BSO), an inhibitor of the enzyme required for GSH synthesis, or when cells were deprived of l-cystine. These findings suggest that glioma cells show an increased requirement for GSH to maintain growth under hypoxic conditions. Therefore, approaches that limit GSH synthesis such as blocking system xc− may be considered as an adjuvant to radiation or chemotherapy. 相似文献
13.
Despite longstanding evidence that hypoglycaemic neuronal injury is mediated by glutamate excitotoxicity, the cellular and molecular mechanisms involved remain incompletely defined. Here, we demonstrate that the excitotoxic neuronal death that follows GD (glucose deprivation) is initiated by glutamate extruded from astrocytes via system xc− – an amino acid transporter that imports l-cystine and exports l-glutamate. Specifically, we find that depriving mixed cortical cell cultures of glucose for up to 8 h injures neurons, but not astrocytes. Neuronal death is prevented by ionotropic glutamate receptor antagonism and is partially sensitive to tetanus toxin. Removal of amino acids during the deprivation period prevents – whereas addition of l-cystine restores – GD-induced neuronal death, implicating the cystine/glutamate antiporter, system xc−. Indeed, drugs known to inhibit system xc− ameliorate GD-induced neuronal death. Further, a dramatic reduction in neuronal death is observed in chimaeric cultures consisting of neurons derived from WT (wild-type) mice plated on top of astrocytes derived from sut mice, which harbour a naturally occurring null mutation in the gene (Slc7a11) that encodes the substrate-specific light chain of system xc− (xCT). Finally, enhancement of astrocytic system xc− expression and function via IL-1β (interleukin-1β) exposure potentiates hypoglycaemic neuronal death, the process of which is prevented by removal of l-cystine and/or addition of system xc− inhibitors. Thus, under the conditions of GD, our studies demonstrate that astrocytes, via system xc−, have a direct, non-cell autonomous effect on cortical neuron survival. 相似文献
14.
Thyroid Hormones Reorganize the Cytoskeleton of Glial Cells Through Gfap Phosphorylation and Rhoa-Dependent Mechanisms 总被引:1,自引:0,他引:1
Zamoner A Funchal C Jacques-Silva MC Gottfried C Barreto Silva FR Pessoa-Pureur R 《Cellular and molecular neurobiology》2007,27(7):845-865
Thyroid hormones (3,5,3′-triiodo-l-thyronine, T3; 3,5,3′,5′-l-tetraiodothyronine, T4; TH) play crucial roles in the growth and differentiation of the central nervous system. In this study, we investigated the
actions of TH on proliferation, viability, cell morphology, in vitro phosphorylation of glial fibrillary acidic protein (GFAP)
and actin reorganization in C6 glioma cells. We first observe that long-term exposure to TH stimulates cell proliferation
without induce cell death. We also demonstrate that after 3, 6, 12, 18, and 24 h treatment with TH, C6 cells and cortical
astrocytes show a process-bearing shape. Furthermore, immunocytochemistry with anti-actin and anti-GFAP antibodies reveals
that TH induces reorganization of actin and GFAP cytoskeleton. We also observe an increased in vitro 32P incorporation into GFAP recovered into the high-salt Triton insoluble cytoskeletal fraction after 3 and 24 h exposure to
5×10−8 and 10−6 M T3, and only after 24 h exposure to 10−9 M T4. These results show a T3 action on the phosphorylating system associated to GFAP and suggest a T3-independent effect of T4 on this cytoskeletal protein. In addition, C6 cells and astrocytes treated with lysophosphatidic acid, an upstream activator
of the RhoA GTPase pathway, totally prevented the morphological alterations induced by TH, indicating that this effect could
be mediated by the RhoA signaling pathway. Considering that IF network can be regulated by phosphorylation leading to reorganization
of IF filamentous structure and that alterations of the microfilament organization may have important implications in glial
functions, the effects of TH on glial cell cytoskeleton could be implicated in essential neural events such as brain development. 相似文献
15.
The effect of ANG II on pHi, [Ca2+]i and cell volume was investigated in T84 cells, a cell line originated from colon epithelium, using the probes BCECF-AM, Fluo
4-AM and acridine orange, respectively. The recovery rate of pHi via the Na+/H+ exchanger was examined in the first 2 min following the acidification of pHi with a NH4Cl pulse. In the control situation, the pHi recovery rate was 0.118 ± 0.001 (n = 52) pH units/min and ANG II (10−12 M or 10−9 M) increased this value (by 106% or 32%, respectively) but ANG II (10−7 M) decreased it to 47%. The control [Ca2+]i was 99 ± 4 (n = 45) nM and ANG II increased this value in a dose-dependent manner. The ANG II effects on cell volume were minor and late
and should not interfere in the measurements of pHi recovery and [Ca2+]i. To document the signaling pathways in the hormonal effects we used: Staurosporine (a PKC inhibitor), W13 (a calcium-dependent
calmodulin antagonist), H89 (a PKA inhibitor) or Econazole (an inhibitor of cytochrome P450 epoxygenase). Our results indicate
that the biphasic effect of ANG II on Na+/H+ exchanger is a cAMP-independent mechanism and is the result of: 1) stimulation of the exchanger by PKC signaling pathway
activation (at 10−12 – 10−7 M ANG II) and by increases of [Ca2+]i in the lower range (at 10−12 M ANG II) and 2) inhibition of the exchanger at high [Ca2+]i levels (at 10−9 – 10−7 M ANG II) through cytochrome P450 epoxygenase-dependent metabolites of the arachidonic acid signaling pathway. 相似文献
16.
Glutamate is stored in synaptic vesicles in presynaptic neurons. It is released into the synaptic cleft to provide signalling
to postsynaptic neurons. Normally, the astroglial glutamate transporters GLT-1 and GLAST take up glutamate to mediate a high
signal-to-noise ratio in the synaptic signalling, and also to prevent excitotoxic effects by glutamate. In astrocytes, glutamate
is transformed into glutamine, which is safely transported back to neurons. However, in pathological conditions, such as an
ischemia or virus infection, astroglial transporters are down-regulated which could lead to excitotoxicity. Lately, it was
shown that even microglia can express glutamate transporters during pathological events. Microglia have two systems for glutamate
transport: GLT-1 for transport into the cells and the xc− system for transport out of the cells. We here review results from our work and others, which demonstrate that microglia
in culture express GLT-1, but not GLAST, and transport glutamate from the extracellular space. We also show that TNF-α can
induce increased microglial GLT-1 expression, possibly associating the expression with inflammatory systems. Furthermore,
glutamate taken up through GLT-1 may be used for direct incorporation into glutathione and to fuel the intracellular glutamate
pool to allow cystine uptake through the xc− system. This can lead to a defence against oxidative stress and have an antiviral function. 相似文献
17.
Corynebacterium acetoacidophilum RYU3161 was cultivated in al-histidine-limited fed-batch culture. To investigate the effect of cell growth on thel-proline production, 5l fed-batch culture was performed using an exponential feeding rate to obtain the specific growth rates (μ) of 0.04, 0.06,
0.08, and 0.1 h−1. The results show that the highest production ofl-proline was obtained at μ=0.04 h−1. The specificl-proline production rate (Qp) increased proportionally as a function of the specific growth rate, but decreased after it revealed the maximum value at
μ=0.08 h−1. Thus, the highest productivity ofl-proline was 1.66 g L−1 h−1 at μ=0.08 h−1. The results show that the production of L-proline inC. acetoacidophilum RYU3161 has mixed growth-associated characteristics. 相似文献
18.
Kim YS Lee JH Kim NH Yeom SJ Kim SW Oh DK 《Applied microbiology and biotechnology》2011,90(2):489-497
In the fed-batch culture of glycerol using a metabolically engineered strain of Escherichia coli, supplementation with glucose as an auxiliary carbon source increased lycopene production due to a significant increase in
cell mass, despite a reduction in specific lycopene content. l-Arabinose supplementation increased lycopene production due to increases in cell mass and specific lycopene content. Supplementation
with both glucose and l-arabinose increased lycopene production significantly due to the synergistic effect of the two sugars. Cell growth by the
consumption of carbon sources was related to endogenous metabolism in the host E. coli. Supplementation with l-arabinose stimulated only the mevalonate pathway for lycopene biosynthesis and supplementation with both glucose and l-arabinose stimulated synergistically only the mevalonate pathway. In the fed-batch culture of glycerol with 10 g l−1 glucose and 7.5 g l−1
l-arabinose, the cell mass, lycopene concentration, specific lycopene content, and lycopene productivity after 34 h were 42 g l−1, 1,350 mg l−1, 32 mg g cells−1, and 40 mg l−1 h−1, respectively. These values were 3.9-, 7.1-, 1.9-, and 11.7-fold higher than those without the auxiliary carbon sources,
respectively. This is the highest reported concentration and productivity of lycopene. 相似文献
19.
Joanna Saluk-Juszczak Beata Olas Barbara Wachowicz Rafal Glowacki Edward Bald 《Cell biology and toxicology》2010,26(4):355-365
The oxidative stress induced by acute exertion may interfere with blood platelet activation. The beneficial effect of l-carnitine (γ-trimethylamino-β-hydroxybutyric acid) on oxidative stress in blood platelets has not been fully investigated;
however, different studies indicate that this compound modulates platelet functions. The aim of our study was to assess the
effects of l-carnitine on platelet activation and oxidative/nitrative protein damage (determined by the levels of protein carbonyl groups,
thiol groups, and 3-nitrotyrosine residues) in resting blood platelets or platelets treated with peroxynitrite (ONOO−, a strong physiological oxidant) in vitro. We also investigated the effects of l-carnitine on the level of platelet glutathione and on the formation of superoxide anion radicals ( O2 - · ) \left( {{\hbox{O}}_2^{ - \bullet }} \right) , lipid peroxidation measured by thiobarbituric acid reactive substances (TBARS) in blood platelets stimulated by thrombin
(a strong physiological agonist), and platelet aggregation induced by adenosine diphosphate (a strong physiological stimulator).
We have observed that carnitine decreases platelet activation (measured by platelet aggregation, the generation of O2 - · {\hbox{O}}_2^{ - \bullet } , and TBARS production). Moreover, our results in vitro demonstrate that carnitine may protect against oxidation of thiol
groups induced by ONOO−. Thus, carnitine may have some protectory effects against oxidative changes induced in blood platelets. 相似文献
20.
Yaser Hassan Dewir Debasis Chakrabarty Mohammed Babar Ali Nisha Singh Eun-Joo Hahn Kee-Yoeup Paek 《Plant Cell, Tissue and Organ Culture》2007,90(3):225-235
Hormonal control of flower induction and inflorescence development in vitro was investigated in Spathiphyllum. The effects of gibberellic acid (GA3) and sucrose on inflorescence development were studied in plantlets regenerated in tissue culture. GA3 was mandatory for the shift from the vegetative to the reproductive stage. The effect of sucrose concentration on inflorescence
bud development was studied in plantlets cultured in MS medium supplemented with 10 mg l−1 GA3. Sucrose concentration at 3 or 6% induced inflorescence development in, respectively, 83–85% of the plantlets. The effect
of GA3 and sucrose on inflorescence differentiation and development were also recorded in liquid culture using air-lift bioreactor.
The best response was found in the same medium which was standardized as an optimum for solid culture, but the results were
better than solid culture. In order to study the relationship between glutathione (GSH) and flowering, we also measured the
oxidized and reduced GSH content in leaves throughout the culture period on 2 weeks interval. The GSH accumulation was more
after 4 weeks until 6 weeks in GA3 treated plantlets. Similarly, glutathione reductase which is involved in the recycling of reduced GSH providing a constant
intracellular level of GSH, was also higher in GA3 treated plantlets. The transient increase in GSH contents also correlated with the changes in measured γ-glutamylcysteine synthetase (γ-ECS) activity over the same period. The antioxidant enzyme activity in GA3 treated plantlets also suggests that the plants suffered increased oxidative stress during the period of GA3 treatment which subsequently increases GSH synthesis through activation of γ-ECS and this promotes flowering by increasing
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