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991.
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993.
Ekaterina Kuznetsova Linda Xu Alexander Singer Greg Brown Aiping Dong Robert Flick Hong Cui Marianne Cuff Andrzej Joachimiak Alexei Savchenko Alexander F. Yakunin 《The Journal of biological chemistry》2010,285(27):21049-21059
Fructose-1,6-bisphosphatase (FBPase), a key enzyme of gluconeogenesis and photosynthetic CO2 fixation, catalyzes the hydrolysis of fructose 1,6-bisphosphate (FBP) to produce fructose 6-phosphate, an important precursor in various biosynthetic pathways. All known FBPases are metal-dependent enzymes, which are classified into five different classes based on their amino acid sequences. Eukaryotes are known to contain only the type-I FBPases, whereas all five types exist in various combinations in prokaryotes. Here we demonstrate that the uncharacterized protein YK23 from Saccharomyces cerevisiae efficiently hydrolyzes FBP in a metal-independent reaction. YK23 is a member of the histidine phosphatase (phosphoglyceromutase) superfamily with homologues found in all organisms. The crystal structure of the YK23 apo-form was solved at 1.75-Å resolution and revealed the core domain with the α/β/α-fold covered by two small cap domains. Two liganded structures of this protein show the presence of two phosphate molecules (an inhibitor) or FBP (a substrate) bound to the active site. FBP is bound in its linear, open conformation with the cleavable C1-phosphate positioned deep in the active site. Alanine replacement mutagenesis of YK23 identified six conserved residues absolutely required for activity and suggested that His13 and Glu99 are the primary catalytic residues. Thus, YK23 represents the first family of metal-independent FBPases and a second FBPase family in eukaryotes. 相似文献
994.
The objective of this investigation was to explore possible molecular changes for role of a high-fat diet (HFD)-induced oxidative stress in splenic lymphocytes, and whether a dietary lipoic acid (LA) supplement could attenuate these changes. Male C57BL/6 mice were fed one of three diets 10 weeks and outcome measures centered on parameters of oxidative stress and lymphocytes apoptosis in spleen. Two-dimensional gel electrophoresis was used to compare the proteomes of splenic lymphocytes with three dietary groups. Differentially expressed spots whose expression altered over three fold were identified by MALDI-TOF MS. In this study, HFD resulted in oxidative stress in mice spleen, and significantly increased apoptotic percentage of splenic lymphocytes. Bioinformatic evaluation results of MALDI-TOF MS showed that 20 differentially expressed protein spots were known to be involved in many processes associated with cell function, such as cytoskeleton, energy metabolism and oxidative stress, signal transduction and cell defense. In conclusion, these results indicate that HFD-induced oxidative stress could lead to the functional decline of splenic lymphocytes, and LA supplement attenuates the alterations of protein expression to maintain the basic biological processes. 相似文献
995.
Rong Zhang Hongzhi Lu Su Tian Jie Yin Qing Chen Li Ma Shijie Cui Yujie Niu 《Chemico-biological interactions》2010,184(3):484-491
Lead (Pb) is a known neurotoxicant in humans and experimental animals. Numerous studies have provided evidence that humans, especially young children, and animals chronically intoxicated with low levels of Pb show learning and memory impairments. Unfortunately, Pb-poisoning cases continue to occur in many countries. Because the current treatment options are very limited, there is a need for alternative methods to attenuate Pb toxicity. In this study, the weaning (postnatal day 21, PND21) rats were randomly divided into five groups: the control group (AIN-93G diet, de-ionized water), the lead acetate (PbAC) group (AIN-93G diet, 2 g/L PbAC in de-ionized water), the lead acetate + WR group (white rice diet, 2 g/L PbAC in de-ionized water; PbAC + WR), the lead acetate + BR group (brown rice diet, 2 g/L PbAC in de-ionized water; PbAC + BR) and the lead acetate + PR group (pre-germinated brown rice diet, 2 g/L PbAC in de-ionized water; PbAC + PR). The animals received the different diets until PND60, and then the experiments were terminated. The protective effects of pre-germinated brown rice (PR) on Pb-induced learning and memory impairment in weaning rats were assessed by the Morris water maze and one-trial-learning passive avoidance test. The anti-oxidative effects of feeding a PR diet to Pb-exposed rats were evaluated. The levels of reactive oxygen species (ROS) were determined by flow cytometry. The levels of 8-hydroxy-2-deoxyguanosine (8-OHdG), γ-aminobutyric acid (GABA) and glutamate were determined by HPLC. Our data showed that feeding a PR diet decreased the accumulation of lead and decreased Pb-induced learning and memory deficits in developing rats. The mechanisms might be related to the anti-oxidative effects and large amount of GABA in PR. Our study provides a regimen to reduce Pb-induced toxicity, especially future learning and memory deficits in the developing brain. 相似文献
996.
Tie-Zhong Cui 《FEBS letters》2010,584(4):652-873
The length of the isoprenoid-side chain in ubiquinone, an essential component of the electron transport chain, is defined by poly-prenyl diphosphate synthase, which comprises either homomers (e.g., IspB in Escherichia coli) or heteromers (e.g., decaprenyl diphosphate synthase (Dps1) and D-less polyprenyl diphosphate synthase (Dlp1) in Schizosaccharomyces pombe and in humans). We found that expression of either dlp1 or dps1 recovered the thermo-sensitive growth of an E. coli ispBR321A mutant and restored IspB activity and production of Coenzyme Q-8. IspB interacted with Dlp1 (or Dps1), forming a high-molecular weight complex that stabilized IspB, leading to full functionality.
Structured summary:
MINT-7385426:Dlp1 (uniprotkb:Q86YH6) and IspB (uniprotkb:P0AD57) physically interact (MI:0915) by blue native page (MI:0276)MINT-7385083, MINT-7385058:IspB (uniprotkb:P0AD57) and IspB (uniprotkb:P0AD57) bind (MI:0407) by blue native page (MI:0276)MINT-7385413:Dlp1 (uniprotkb:O13851) and IspB (uniprotkb:P0AD57) physically interact (MI:0915) by blue native page (MI:0276)MINT-7385024:IspB (uniprotkb:P0AD57) physically interacts (MI:0915) with Dps1 (uniprotkb:O43091) by pull down (MI:0096)MINT-7385041:IspB (uniprotkb:P0AD57) physically interacts (MI:0915) with Dlp1 (uniprotkb:O13851) by pull down (MI:0096)MINT-7385388:IspB (uniprotkb:P0AD57) and Dps1 (uniprotkb:O43091) physically interact (MI:0915) by blue native page (MI:0276) 相似文献997.
Philipp S Cui L Ludolph B Kelm M Schulz R Cohen MV Downey JM 《American journal of physiology. Heart and circulatory physiology》2006,290(1):H450-H457
Protection from a prolyl hydroxylase domain-containing enzyme (PHD) inhibitor, desferoxamine (DFO), was recently reported to be dependent on production of reactive oxygen species (ROS). Ischemic preconditioning triggers the protected state by stimulating nitric oxide (NO) production to open mitochondrial ATP-sensitive K+ (mitoK(ATP)) channels, generating ROS required for protection. We tested whether DFO and a second PHD inhibitor, ethyl-3,4-dihydroxybenzoate (EDHB), might have similar mechanisms. EDHB and DFO increased ROS generation by 50-75% (P < 0.001) in isolated rabbit cardiomyocytes. This increase after EDHB exposure was blocked by N(omega)-nitro-L-arginine methyl ester (L-NAME), an NO synthase (NOS) inhibitor; ODQ, a guanylyl cyclase antagonist; and Rp-8-bromoguanosine-3',5'-cyclic monophosphorothioate Rp isomer, a PKG blocker, thus implicating the NO pathway in EDHB's signaling. Glibenclamide, a nonselective K(ATP) channel blocker, or 5-hydroxydecanoate, a selective mitoK(ATP) channel antagonist, also prevented EDHB's ROS production, as did blockade of mitochondrial electron transport with myxothiazol. NOS is activated by Akt. However, neither wortmannin, an inhibitor of phosphatidylinositol-3-kinase, nor Akt inhibitor blocked EDHB-induced ROS generation, indicating that EDHB initiates signaling downstream of Akt. DFO also increased ROS production, and this effect was blocked by ODQ, 5-hydroxydecanoate, and N-(2-mercaptopropionyl)glycine, an ROS scavenger. DFO increased cardiomyocyte production of nitrite, a metabolite of NO, and this effect was blocked by an inhibitor of NOS. DFO also spared ischemic myocardium in intact hearts. This infarct-sparing effect was blocked by ODQ, L-NAME, and N-(2-mercaptopropionyl)glycine. Hence, DFO and EDHB stimulate NO-dependent activation of PKG to open mitoK(ATP) channels and produce ROS, which act as second messengers to trigger entrance into the preconditioned state. 相似文献
998.
999.
Xia Z Taylor PR Locklin RM Gordon S Cui Z Triffitt JT 《Journal of cellular biochemistry》2006,98(4):966-980
Immunocompromised mouse models have been extensively used to assess human cell implantation for evaluation of cytotherapy, gene therapy and tissue engineering strategies, as these mice are deficient in T and B lymphoid cells. However, the innate immune response and its effect on human cell xenotransplantation in these mouse models are mainly unknown. The aim of this study is to characterise the myeloid populations in the spleen and blood of CB17 scid beige (CB17 sb) mice, and to study the inflammatory cell responses to xenogeneic implantation of enhanced green fluorescent protein (GFP)-labelled human bone marrow fibroblastic (HBMF) cells into CB17 sb mice. The results indicate that even though CB17 sb mice are deficient in B- and T-cells, they exhibit some increases in their monocyte (Mo), macrophage (Mphi) and neutrophil (Neu) populations. NK cell and eosinophil populations show no differences compared with wild-type Balb/C mice. An innate immune response, identified by CR3 (CD11b/CD18)-positive myeloid inflammatory cells and F4/80-positive macrophages, was evident in the tissues where HBMF cells were implanted. As a consequence, the majority of implanted HBMF cells were eliminated by 4 weeks after implantation. Interestingly, the mineralised matrix formed by osteogenic HBMF cells was also eroded by multinuclear Mphi-like giant cells. We conclude that CB17 sb mice retain active innate immune cells, which respond to HBMF cell xenotransplantation. This study highlights the importance of the innate immune cells in the anti-xenograft response and suggests that strategies to block the activities of these cells may ameliorate the progressive long-term elimination of xenotransplants. 相似文献
1000.
Expression pattern shifts following duplication indicative of subfunctionalization and neofunctionalization in regulatory genes of Arabidopsis 总被引:1,自引:0,他引:1
Duarte JM Cui L Wall PK Zhang Q Zhang X Leebens-Mack J Ma H Altman N dePamphilis CW 《Molecular biology and evolution》2006,23(2):469-478
Gene duplication plays an important role in the evolution of diversity and novel function and is especially prevalent in the nuclear genomes of flowering plants. Duplicate genes may be maintained through subfunctionalization and neofunctionalization at the level of expression or coding sequence. In order to test the hypothesis that duplicated regulatory genes will be differentially expressed in a specific manner indicative of regulatory subfunctionalization and/or neofunctionalization, we examined expression pattern shifts in duplicated regulatory genes in Arabidopsis. A two-way analysis of variance was performed on expression data for 280 phylogenetically identified paralogous pairs. Expression data were extracted from global expression profiles for wild-type root, stem, leaf, developing inflorescence, nearly mature flower buds, and seedpod. Gene, organ, and gene by organ interaction (G x O) effects were examined. Results indicate that 85% of the paralogous pairs exhibited a significant G x O effect indicative of regulatory subfunctionalization and/or neofunctionalization. A significant G x O effect was associated with complementary expression patterns in 45% of pairwise comparisons. No association was detected between a G x O effect and a relaxed evolutionary constraint as detected by the ratio of nonsynonymous to synonymous substitutions. Ancestral gene expression patterns inferred across a Type II MADS-box gene phylogeny suggest several cases of regulatory neofunctionalization and organ-specific nonfunctionalization. Complete linkage clustering of gene expression levels across organs suggests that regulatory modules for each organ are independent or ancestral genes had limited expression. We propose a new classification, regulatory hypofunctionalization, for an overall decrease in expression level in one member of a paralogous pair while still having a significant G x O effect. We conclude that expression divergence specifically indicative of subfunctionalization and/or neofunctionalization contributes to the maintenance of most if not all duplicated regulatory genes in Arabidopsis and hypothesize that this results in increasing expression diversity or specificity of regulatory genes after each round of duplication. 相似文献