共查询到20条相似文献,搜索用时 46 毫秒
1.
Jesudason EP Masilamoni JG Ashok BS Baben B Arul V Jesudoss KS Jebaraj WC Dhandayuthapani S Vignesh S Jayakumar R 《Molecular and cellular biochemistry》2008,311(1-2):145-156
Aβ amyloid peptide is believed to induce oxidative stress leading to inflammation, which is postulated to play a significant
role in the toxicity of Alzheimer’s disease (AD). This study was designed to investigate the inhibitory effects of dl-α lipoic acid (LA), a potential free radical scavenger, on oxidative vulnerability induced by intraperitoneal injection of
Aβ25–35 amyloid fibrils in mice. Mice were divided into three groups: control, Aβ amyloid toxicity induced (AT), and LA treated (ATL).
Blood Plasma was separated, liver, spleen and brain were dissected and analysis of oxidants, antioxidants, ATPases, glial
fibrillary acidic protein (GFAP) and nuclear factor kappa-B (NFκB) were carried out. Results show biochemical parameters such
as reactive oxygen species (ROS) and lipid peroxidation (LPO) were significantly lowered (P < 0.05) and levels of antioxidants and ATPase (P < 0.05) were significantly increased (P < 0.05) in hepatocytes, splenocytes and astrocytes of the ATL group. Moreover, our histological results revealed a decreased
GFAP immunoreactivity in the neocortical region and NFκB immunoreactivity in neocortex, liver and spleen. This study reiterates
LA as a potent free radical scavenger to combat oxidative vulnerability in the treatment for Aβ amyloid toxicity. 相似文献
2.
Cai Zhiyou Yan Yong Sun Shanquan Zhang Jun Huang Liangguo Yan Ling Li Jieying 《Neurochemical research》2009,34(7):1226-1235
Chronic cerebral hypoperfusion (CCH) increases the risk of Alzheimer disease (AD) through several biologically plausible pathways,
but the relationship between CCH and the development of AD remains uncertain. To investigate expression of APP, BACE1 and
Aβ in the hippocampus of BCCAO rats and study pathophysiological mechanism of AD from CCH. CCH rat model was established by
chronic bilateral common carotid artery occlusion (BCCAO). Behavior was evaluated after BCCAO with Morris water maze and open-field
task. Expression of Aβ was measured by enzyme linked immunosorbent assay (ELISA). β-Amyloid precursor protein cleavage enzyme
1 (BACE1) and β-amyloid precursor protein (APP) were tested by ELISA, Western blotting and RT-PCR. Cognitive impairment occurred
with CCH by Morris water maze test and open-field task. The BACE1 and Aβ level in BCCAO rats was more increased than sham-operation
control rats (P < 0.01) but APP had no difference(P > 0.05). The expression of BACE1 and Aβ has no inter-grouop difference in BCCAO rats (P > 0.05). The level of BACE1 and Aβ had positive correlation with cognitive impairment (P < 0.01) while no correlation was observed between APP and cognitive impairment. Chronic cerebral ischemia contributes to
cognitive impairment and vascular pathogenesis of Alzheimer’s disease that chronic cerebral hypoperfusion increases BACE1
and Aβ level in brain. 相似文献
3.
Sacco C Skowronsky RA Gade S Kenney JM Spuches AM 《Journal of biological inorganic chemistry》2012,17(4):531-541
Metal ions have been shown to play a critical role in β-amyloid (Aβ) neurotoxicity, thus prompting an intense investigation
into the formation of metal–Aβ complexes. Isothermal titration calorimetry (ITC) has been widely used to determine binding
constants (K) for a variety of metal–protein interactions, including those in metal–Aβ complexes. In this study, ITC was used to more
fully quantify the thermodynamics (K, ΔG, ΔH, and TΔS) of Cu2+ binding to Aβ16, N-acetyl-Aβ16, Aβ28, N-acetyl-Aβ28, and Aβ28 variants (H6A, H13A, H14A) at pH 7.4 and 37 °C. After deconvolution of competing reactions, K for Aβ16 was found to be 1.1 (±0.13) × 109 and is in strong agreement with literature values measured under similar conditions. Further, a similar K value was obtained at two additional concentrations of competing ligand, suggesting that ternary complex formation is not
significant. The acetylated peptide analogs reveal a marked decrease in the overall free energy upon binding, which is the
result of less favorable enthalpic and entropic contributions. Circular dichroism spectroscopy shows conformational changes
that are consistent with these results. Most importantly, data for Aβ28 variants lacking a potential Cu2+-binding histidine residue reveal that the overall free energy of binding remains constant, which is the result of entropy/enthalpy
compensation. These data provide fundamental thermodynamic evidence for coordination plasticity in Cu2+ binding to Aβ and other intrinsically disordered peptides. 相似文献
4.
D. Vidović N. Boulanger Olabisi Kuye Joyce Toral Kouichi Ito Jeanmarie Guenot Horst Bluethmann Zoltan A. Nagy 《Immunogenetics》1997,45(5):325-335
Mutant mice generated by disrupting the H2-Aa
b
major histocompatibility complex (Mhc) gene are demonstrated here to express Aβb chains in the absence of α chains. These mice possess a CD4+ helper T cell (Th) repertoire that uses predominantly the Vβ7 T-cell antigen receptor (Tcr) segment for recognition of any
protein antigen presented by the α-free Aβ molecule. As an alloantigen, the Aα-free Aβ molecule is recognized very poorly
by T cells from a series of class II disparate mouse strains, indicating that it is grossly different from normal α/β heterodimers.
Indeed, molecular modeling suggests a β/β homodimer arrangement with an altered geometry of the Tcr contact area. Interestingly,
the mutant mice exhibit normal alloreactivity, without a restricted Vβ usage, toward a series of foreign α/β class II heterodimers,
although their T cells developed in the absence of such heterodimers. Thus, the complementarity of Tcr to normal α/β heterodimers,
and thereby also alloreactivity, appears to be an ontogeny independent (i. e., germline-encoded) feature.
Received: 30 September 1996 / Revised: 18 October 1996 相似文献
5.
Monge-Argilés JA Muñoz-Ruiz C Pampliega-Pérez A Gómez-López MJ Sánchez-Payá J Rodríguez Borja E Ruiz-Vegara M Montoya-Gutiérrez FJ Leiva-Santana C 《Neurochemical research》2011,36(6):986-993
The study of biomarkers in the cerebrospinal fluid (CSF) of patients with mild cognitive impairment (MCI) is a technique used
with increasing frequency in the early diagnosis of Alzheimers disease (AD). Our objectiv was to gain an own experience while
evaluating the reliability, sensitivity, and reproducibility of this technique in Spanish patients. Thirty-seven patients
with MCI and twenty-four control subjects were studied by means of AD biomarker analysis in CSF. xMAP Luminex and INNO-BIA
Alzbio3 reagents of Innogenetics were used. The study variables assessed were levels of Aβ1–42, T-tau and P-tau181p proteins as well as the ratios of T-tau/Aβ1–42 and P-tau181p/Aβ1–42. Samples from nineteen patients were examined twice. Intra-class correlation coefficients for the three biomarkers used showed
values higher than 0.95. We observed significant differences between the control group and the MCI groups. In the 6 months
following lumbar puncture (LP), eleven (29%) patients with MCI developed AD. These patients showed significant lower levels
in Aβ1–42 protein (276.35 ± 78 vs. 367.13 ± 123.49, P < 0.03) and higher ratios (T-tau/Aβ1–42 [0.38 ± 0.2 vs. 0.22 ± 0.14, P < 0.01] and P-tau181p/Aβ1–42 [0.27 ± 0.13 vs. 0.16 ± 0.1, P < 0.008]) to those in the same group who remained stable. We obtained similar results to those in the most recent reliable
literature with our ROC curves, especially with our P-tau181p values and T-tau/Aβ1–42 ratio in order to differentiate between control and AD groups. Our experience showed that the analysis of CSF-AD biomarkers
in patients with MCI is reliable, sensitive and reproducible. In our knowledge, this is the first experience in Spanish patients. 相似文献
6.
Feda E. Ali Kevin J. Barnham Colin J. Barrow Frances Separovic 《International journal of peptide research and therapeutics》2003,10(5-6):405-412
Summary Metal-catalyzed oxidation (MCO) can lead to damage of bio-molecules and is implicated in neurodegenerative diseases, such
as Alzheimer's disease (AD). The amino acid residues, tyrosine, histidine and methionine, have been proposed to play important
roles in metal mediated oxidative stress and subsequent reactions of amyloid β peptide (Aβ) a major contributor in the pathogenesis
of AD. The MCO of Aβ residues, particularly histidine, methionine and tyrosine, and reviewed. MCO of Aβ histidine and tyrosine
residues can facilitate oligomerization and may play a role in both amyloid formation and Aβ neurotoxicity. Further work is
needed to determine the importance of Aβ oxidation in AD and the role of Aβ oxidation products and oxidative stress in disease
progression. The mechanisms of Aβ MCO are complex and multiple reaction products can form. Further study is needed to determine
the mechanisms by which Aβ MCO occursin vivo. In addition, new analytical methods are required to monitor the formation of Aβ MCO products formed during AD. The copper-H2O2 redox system provides a chemical model by which Aβ MCO can be studiedin vitro and can be used to produce oxidatively modified amino acid residues for use as standards in developing new analytical methods
to monitor Aβ MCO. 相似文献
7.
We have investigated the neuroprotective effect of sesaminol glucosides (SG) in SK-N-SH cells. SG prevented apoptotic cell
death induced by Aβ25–35. In parallel, SK-N-SH cells exposed to Aβ25–35 underwent oxidative stress as shown by the elevated level of intracellular ROS, lipid peroxidation, and 8-hydroxy-2′-deoxyguanosine
(8-OHdG) formation, which were effectively suppressed by SG treatment. Furthermore, SG reversed the activities of catalase
and glutathione peroxidase, and restored intracellular GSH levels in Aβ25–35 challenged SK-N-SH cells. In addition, SG inhibited not only Aβ25–35-induced apoptotic features including cleavage of poly(ADP-ribose) polymerase, activation of caspase-3, and activation of
caspase-9, but also elevated Bax/Bcl-2 ratio in SK-N-SH cells treated with Aβ25–35. It was also observed that Aβ25–35 stimulated the phosphorylation of mitogen-activated protein kinases (MAPKs), including extracellular protein regulated protein
kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAP kinase. SG inhibited phosphorylation of the JNK, ERK and p38 MAP
kinase. These results suggest that SG has a protective effect against Aβ25–35-induced neuronal apoptosis, possibly through scavenging oxidative stress and regulating MAPKs signaling pathways. 相似文献
8.
Aneta Monika Białkowska Hubert Cieśliński Karolina Maria Nowakowska Józef Kur Marianna Turkiewicz 《Archives of microbiology》2009,191(11):825-835
A psychrotrophic bacterium producing a cold-adapted β-galactosidase upon growth at low temperatures was classified as Arthrobacter sp. 20B. A genomic DNA library of strain 20B introduced into Escherichia coli TOP10F′ and screening on X-Gal (5-bromo-4-chloro-3-indolyl-β-d-galactopyranoside)-containing agar plates led to the isolation of β-galactosidase gene. The β-galactosidase gene (bgaS) encoding a protein of 1,053 amino acids, with a calculated molecular mass of 113,695 kDa. Analysis of the amino acid sequence
of BgaS protein, deduced from the bgaS ORF, suggested that it is a member of the glycosyl hydrolase family 2. A native cold-adapted β-galactosidase was purified
to homogeneity and characterized. It is a homotetrameric enzyme, each subunit being approximately 116 kDa polypeptide as deduced
from native and SDS–PAGE, respectively. The β-galactosidase was optimally active at pH 6.0–8.0 and 25°C. P-nitrophenyl-β-d-galactopyranoside (PNPG) is its preferred substrate (three times higher activity than for ONPG—o-nitrophenyl-β-d-galactopyranoside). The Arthrobacter sp. 20B β-galactosidase is activated by thiol compounds (53% rise in activity in the presence of 10 mM 2-mercaptoethanol),
some metal ions (activity increased by 50% for Na+, K+ and by 11% for Mn2+) and inactivated by pCMB (4-chloro-mercuribenzoic acid) and heavy metal ions (Pb2+, Zn2+, Cu2+). 相似文献
9.
Michael J. Bosela 《Plant Cell, Tissue and Organ Culture》2009,98(3):249-261
The effects of β-lactam antibiotics (penicillin, carbenicillin and cefotaxime), cytokinins, and auxins including phenylacetic
acid, a β-lactam breakdown product, were evaluated during in vitro shoot morphogenesis in two hybrid aspens; P. tremuloides × P. tremula (XTTa) and P. x canescens × P. grandidentata (XCaG). Although different callus and shoot induction media were used for both hybrids, the β-lactams often engendered similar
responses. At concentrations of 1,000 mg l−1, carbenicillin adversely impacted shoot elongation and, to a lesser degree, shoot regeneration. Cefotaxime enhanced caulogenesis
for all of the concentrations evaluated (125–500 mg l−1) especially when the cytokinin thidiazuron was used for shoot induction. The shoots formed faster and in greater numbers;
and the improvements were significant (α = 0.05) for both hybrids. However, hyperhydricity was more problematic when cefotaxime was included in the media. The incidence
of shoot hyperhydricity for the XCaG hybrid was more than twice as great for the highest cefotaxime concentration evaluated
(500 mg l−1) than for the control (>90% vs. ~40%). Penicillin had an opposite effect. Hyperhydricity frequencies for the XCaG hybrid
were lower when the media were supplemented with penicllin and the reductions were statistically significant at concentrations
of 500–1,000 mg l−1. The effects of the antibiotics were generally not reproduced by the auxins (0.1–100 μM), including phenylacetic acid, or
the other potential β-lactam degradation products evaluated (e.g. phenylmalonic acid, aminopenicillanic acid). The antibiotics
may have affected shoot hyperhydicity indirectly via changes in the time course of shoot regeneration. 相似文献
10.
Synowiec E Szaflik J Chmielewska M Wozniak K Sklodowska A Waszczyk M Dorecka M Blasiak J Szaflik JP 《Molecular biology reports》2012,39(3):2081-2087
Iron may be implicated in the generation of oxidative stress by the catalyzing the Haber–Weiss or Fenton reaction. On the
other hand, oxidative stress has been implicated in the pathogenesis of age-related macular degeneration (AMD) and heme oxygenase-1
(HO-1), encoded by the HMOX1 gene and heme oxygenase-2 (HO-2), encoded by the HMOX2 gene are important markers of iron-related oxidative stress and its consequences. Therefore, variability of the HMOX1 and HMOX2 genes might be implicated in the pathogenesis of AMD through the modulation of the cellular reaction to oxidative stress.
In the present work, we investigated the association between AMD and a G → C transversion at the 19 position in the HMOX1 gene (the 19G>C-HMOX1 polymorphism, rs2071747) and a A → G transition at the −42 + 1444 position in the HMOX2 gene (the −42 + 1444A>G-HMOX2 polymorphism, rs2270363) and its modulation by some environmental factors. 279 patients with AMD and 105 controls were recruited
in this study and the polymorphisms were typed by restriction fragment length polymorphism and allele-specific polymerase
chain reaction (PCR). We observed an association between the occurrence of dry AMD and the G/A genotype of the −42 + 1444A>G-HMOX2 polymorphism (odds ratio (OR) 2.72), whereas the G/G genotype reduced the risk of dry AMD (OR 0.41). The G/C genotype and
the C allele of the 19 G>C-HMOX1 polymorphism and the G/G genotype and the G allele of the −42 + 1444A>G-HMOX2 polymorphism were associated with progression of AMD from dry to wet form (OR 4.83, 5.20, 2.55, 1.69, respectively). On the
other hand, the G/G genotype and the G allele of the 19 G>C-HMOX1 polymorphism and the A/G genotype and the A allele of the −42 + 1444A>G-HMOX2 polymorphism protected against AMD progression (OR 0.19, 0.19, 0.34, 0.59, respectively). Therefore, the 19G>C-HMOX1 and the −42 + 1444A>G-HMOX2 polymorphisms may be associated with the occurrence and progression of AMD. 相似文献
11.
Yogita Mantri Marco Fioroni Mu-Hyun Baik 《Journal of biological inorganic chemistry》2008,13(8):1197-1204
One of the many hypotheses on the pathogenesis of Alzheimer’s disease is that the amyloid-β peptide (Aβ) binds CuII and can catalytically generate H2O2, leading to oxidative damage in brain tissues. For a molecular level understanding of such catalysis it is critical to know
the structure of the Aβ–CuII complex precisely. Unfortunately, no high-resolution structure is available to date and there is considerable debate over
the copper coordination environment with no clear consensus on which residues are directly bound to CuII. Considering all plausible isomers of the copper-bound Aβ42 and Aβ40 using a combination of density functional theory and
classical molecular dynamics methods, we report an atomic resolution structure for each possible complex. We evaluated the
relative energies of these isomeric structures and surprisingly found that Aβ42 and Aβ40 display very different binding modes,
suggesting that shorter peptides that are truncated at the C-terminus may not be realistic models for understanding the chemistry
of the most neurotoxic peptide, Aβ42.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
12.
Yurong Zhang Zuyi Yuan Heng Ge Yanping Ren 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》2010,180(1):117-124
To examine the effects of chronic ouabain treatment on blood pressure (BP), sodium excretion, and renal dopamine D1 receptor level, male Sprague-Dawley (SD) rats were treated with ouabain (27.8 μg kg−1 d−1) intraperitoneally for 5 weeks, and systolic blood pressure (SBP) were recorded weekly. After 5 weeks, sodium excretion and
dopamine D1 receptor agonist fenoldopam-mediated natriuresis were measured, and the expression and phosphorylation levels of the renal
cortical dopamine D1 receptor were confirmed by Western blot analysis. The effects of ouabain on fenoldopam-mediated inhibition of Na+-K+-ATPase activity were determined by colorimetric assays in human proximal tubular epithelial cells (HK-2 cells). After 5 weeks,
the SBP in ouabain group was significantly higher than that in the control group (P < 0.01), but the sodium excretion and renal cortical D1 receptor expression levels were reduced, and D1 receptor phosphorylation levels were increased after ouabain treatment. Intravenous administration of fenoldopam caused an
increased sodium excretion in control rats, but failed to induce natriuresis in ouabain-treated rats. In addition, fenoldopam
induced a dose–respone (10−9 to 10−6 M) inhibition of Na+-K+-ATPase activity in HK-2 cells,but these effects were significantly diminished in HK-2 cells pretreated with nanomolar concentration
of ouabain for 5 days (P < 0.01). We propose that the ouabain-induced reduction of the renal dopamine D1 receptor function serves as a mechanism responsible for sodium retention, and this contributes to the hypertension induced
by chronic ouabain treatment. 相似文献
13.
Previous studies in expression systems have found different ion activation of the Na+/K+-ATPase isozymes, which suggest that different muscles have different ion affinities. The rate of ATP hydrolysis was used
to quantify Na+,K+-ATPase activity, and the Na+ affinity of Na+,K+-ATPase was studied in total membranes from rat muscle and purified membranes from muscle with different fiber types. The
Na+ affinity was higher (K
m lower) in oxidative muscle compared with glycolytic muscle and in purified membranes from oxidative muscle compared with
glycolytic muscle. Na+,K+-ATPase isoform analysis implied that heterodimers containing the β1 isoform have a higher Na+ affinity than heterodimers containing the β2 isoform. Immunoprecipitation experiments demonstrated that dimers with α1 are responsible for approximately 36% of the total Na,K-ATPase activity. Selective inhibition of the α2 isoform with ouabain suggested that heterodimers containing the α1 isoform have a higher Na+ affinity than heterodimers containing the α2 isoform. The estimated K
m values for Na+ are 4.0, 5.5, 7.5 and 13 mM for α1β1, α2β1, α1β2 and α2β2, respectively. The affinity differences and isoform distributions imply that the degree of activation of Na+,K+-ATPase at physiological Na+ concentrations differs between muscles (oxidative and glycolytic) and between subcellular membrane domains with different
isoform compositions. These differences may have consequences for ion balance across the muscle membrane. 相似文献
14.
Xianyong Lan Xinsheng Lai Zhuanjian Li Jing Wang Chuzhao Lei Hong Chen 《Molecular biology reports》2010,37(1):441-449
HESX1 plays a key role in the development of the forebrain and pituitary gland and produces potential effects on performance
traits. The objective of this study was to detect and assess the associations of the possible polymorphisms of six loci within
HESX1 gene with performance traits in Chinese 1,119 goats. Only one novel SNP (NM_001494116:g.307049A > G) locating on IVS1 + 348A > G
was identified and detected by HaeIII forced-RFLP-PCR. The frequencies of allele “G” varied from 0.025 to 0.245 in analyzed populations with the Hardy–Weinberg
equilibrium (P > 0.05). Genotypic and allelic frequencies were found to be significantly different in four breeds (χ2 = 147.674, df = 6, P < 0.001; χ2 = 157.250, df = 3, P < 0.001, respectively), implying that the distribution of genotypic and allelic frequencies of goat HESX1 gene was significantly associated with different goat utilities (cashmere, meat and dairy). Association analysis results
revealed no significant effects of caprine HESX1 gene on body sizes in XNSN population (P > 0.05) and cashmere traits in IMWC population (P > 0.05). Significant statistical of HESX1 gene with body weight was found (*P < 0.05). The genotype AA showed significantly higher body weight than those of AG in 2-year-old age (*P < 0.05), while the AA genotype was senior to AG genotype in 4-year-old body weight trait (*P < 0.05). These suggestions indicated that the HESX1 gene has significant effect on goat body weight depending on ages, which is accordance with the function repressor of the
HESX1. 相似文献
15.
Sobel ES Brusko TM Butfiloski EJ Hou W Li S Cuda CM Abid AN Reeves WH Morel L 《Arthritis research & therapy》2011,13(3):R106
Introduction
CD25+ FOXP3+ CD4+ regulatory T cells (Tregs) are induced by transforming growth factor β (TGFβ) and further expanded by retinoic acid (RA). We have previously shown that this process was defective in T cells from lupus-prone mice expressing the novel isoform of the Pbx1 gene, Pbx1-d. This study tested the hypothesis that CD4+ T cells from systemic lupus erythematosus (SLE) patients exhibited similar defects in Treg induction in response to TGFβ and RA, and that PBX1-d expression is associated with this defect. 相似文献16.
Yi-Hsun Chang Yuan-Liang Wang Jain-Yu Lin Lea-Yea Chuang Chi-Ching Hwang 《Molecular biotechnology》2010,44(2):133-139
Human 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) catalyzes the reaction of estrone with NADPH to form estradiol and
NADP+, thereby regulating the biological activity of sex steroid hormones in a variety of tissues. Here, we present an efficient
method for expressing and purifying human 17β-HSD1 from Escherichia coli. The expression vector pET28a/17β-HSD1 was constructed and transformed into Escherichia coli BL21(DE3) cells. We found that the active enzyme can be obtained by inducing 17β-HSD1 expression at 0.25 mM IPTG, 13°C for
overnight. The protein is purified by single step Ni–NTA affinity chromatography and yields 2.8 mg/L of culture. The kinetic
study shows V/E
t
of (1.21 ± 0.05) × 10−2/s and K
estradiol of 0.8 μM in the oxidation of estradiol with NADP+ as cofactor at pH 9.3. The new bacterial expression system for recombinant 17β-HSD1 is useful for the easy purification of
large amounts and will facilitate the functional study of this enzyme. 相似文献
17.
Sokolova TV Zakharova IO Furaev VV Rychkova MP Avrova NF 《Neurochemical research》2007,32(8):1302-1313
Ganglioside GM1 was shown to increase the viability of PC12 cells exposed to hydrogen peroxide or amyloid β-peptide (Aβ25–35). The PC12 cells transfected with mutant gene (expressing APPSW) were found to be more sensitive to oxidative stress than the cells transfected with wild type gene (expressing APPWT) or vector-transfected cells, GM1 being effective in enhancing the viability of the cells transfected with mutant gene. The
exposure to hydrogen peroxide or Aβ25–35 results in a partial inactivation of Na+,K+-ATPase in PC12 cells, H2O2 increases MDA accumulation in these cells. But these effects could be partially prevented or practically abolished by GM1
ganglioside. In the presence of the inhibitor of tyrosine kinase of Trk receptors (K-252a) the protective and metabolic effects
of GM1 on PC12 cells in conditions of oxidative stress caused by hydrogen peroxide are not observed or are markedly diminished. 相似文献
18.
Luc Guilloreau Luminita Damian Yannick Coppel Honoré Mazarguil Mathias Winterhalter Peter Faller 《Journal of biological inorganic chemistry》2006,11(8):1024-1038
The aggregation of the peptide amyloid-β (Aβ) to form amyloid plaques is a key event in Alzheimer’s disease. It has been shown that CuII can bind to soluble Aβ and influence its aggregation properties. Three histidines and the N-terminal amine have been proposed to be involved in its coordination. Here, for the first time, we show isothermal titration calorimetry (ITC) measurements of the CuII binding to Aβ16 and Aβ28, models of the soluble Aβ. Moreover, different spectroscopic methods were applied. The studies revealed new insights into these CuII–Aβ complexes: (1) ITC showed two CuII binding sites, with an apparent K
d of 10−7 and 10−5 M, respectively; (2) the high-affinity site has a smaller enthalpic contribution but a larger entropic contribution than the low-affinity binding site; (3) azide did not bind to CuII in the higher-affinity binding site, suggesting the absence of a weak, labile ligand; (4) azide could bind to the CuII in the low-affinity binding site in Aβ28 but not in Aβ16; (5) 1H-NMR suggests that the carboxylate of aspartic acid in position 1 is involved in the ligation to CuII in the high-affinity binding site; (6) the pK
a of 11.3 of tyrosine in position 10 was not influenced by the binding of 2 equivalents of CuII.Electronic Supplementary Material Supplementary material is available to authorized users in the online version of this article at . 相似文献
19.
Long-term alcohol consumption can cause oxidative stress and cytokines induction, which are associated with free radicals.
Quercetin, one of the most widely distributed flavonoids in plants, is a natural antioxidant. We investigated the hypothesis
that quercetin could prevent the ethanol-induced oxidative stress and decreases tumor necrosis factor-α (TNF-α) and interferon-γ
(INF-γ) as pro-inflammatory cytokines. Twenty-eight rats were randomly divided into control group (C), ethanol treatment group
(EtOH) (~1 ml/day, 80%; 2 g/kg body wt), intragastrically (i.g.), quercetin treatment group (Q), (100 mg/kg-body wt per 3 days)
i.g. and ethanol plus quercetin treatment group (EtOH + Q) (1 ml/day, 80% of ethanol and 100 mg/kg-body wt of quercetin per
3 days) i.g. for 30 days Plasma thiobarbituric acid reactive substance (TBARS) levels and protein carbonyl content were significantly
higher in the EtOH group than the C group (P < 0.01). On the other hand, TBARS level and protein carbonyl content in the EtOH + Q group was decreased significantly by
quercetin (P < 0.05, P < 0.01; respectively). While GSH levels in whole blood decreased in EtOH group compared to C group, they increased significantly
by quercetin (P < 0.05). Plasma ALT, TNF-α and IFN-γ levels increased significantly in the EtOH group compared to control group (P < 0.05, P < 0.01, P < 0.01, respectively), but they decreased significantly in the EtOH + Q group in comparison with EtOH group (P < 0.05, P < 0.01, P < 0.01, respectively). Our results demonstrate that quercetin treatment may provide a protection as reflected by decreased
plasma TBARS, protein carbonyls, TNF-α, INF-γ and ALT levels against ethanol-induced oxidative damage. 相似文献
20.
Jesudason EP Baben B Ashok BS Masilamoni JG Kirubagaran R Jebaraj WC Jayakumar R 《Molecular and cellular biochemistry》2007,298(1-2):69-81
Aβ vaccination as a therapeutic intervention of Alzheimer’s has many challenges, key among them is the regulation of inflammatory
processes concomitant with excessive generation of free radicals seen during such interventions. Here we report the beneficial
effects of melatonin on inflammation associated with Aβ vaccination in the central and peripheral nervous system of mice.
Mice were divided into three groups (n = 8 in each): control, inflammation (IA), and melatonin-treated (IAM). The brain, liver, and spleen samples were collected
after 5 days for quantitative assessment of plasma lipid peroxides (LPO), an oxidative stress marker, and antioxidant enzymes
such as superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione peroxidase (Gpx). IA group mice have
shown the elevated concentration of LPO significantly while there was a reduction at antioxidant enzyme levels. In addition,
a significant (P < 0.05) reduction in neurotransmitters like dopamine (DA), 5-hydroxytryptamine (5-HT), and norepinephrine (NE) was also observed
in the IA group mice. Nevertheless, their metabolites, such as homovanillic acid (HVA) and 5-hydroxyindole acetic acid (5-HIAA)
increased significantly (P < 0.05) as compared to control. Samples were further evaluated at microscopic level to examine the neuropathological changes
by immunohistochemical methods. Melatonin treatment effectively reversed these above changes and normalized the LPO and antioxidant
enzyme levels (P < 0.05). Furthermore, melatonin salvaged the brain cells from inflammation. Our Immunohistochemical findings in the samples
of melatonin-treated animals (IAM group) indicated diminished expression of glial fibrillary acidic protein (GFAP) and nuclear
factor kappa B (NfκB) than those observed in the IA group samples. Our results suggest that administration of melatonin protects
inflammation associated with Aβ vaccination, through its direct and indirect actions and it can be an effective adjuvant in
the development of vaccination in immunotherapy for Alzheimer’s disease (AD). 相似文献