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At least 217 records · Page 12Linked to original sources
PubMed1999

The acceptor substrate specificity of human beta4-galactosyltransferase V indicates its potential function in O-glycosylation.

In order to assess the function of the different human UDP-Gal:GlcNAc beta4-galactosyltransferases, the cDNAs of two of them, beta4-GalT I and beta4-GalT V, were expressed in the baculovirus/insect cell expression system. The soluble recombinant enzymes produced were purified from the medium and used to determine their in vitro substrate specificities. The specific activity of the recombinant beta4-GalT V was more than 15 times lower than that of beta4-GalT I, using GlcNAc beta-S-pNP as an acceptor. Whereas beta4-GalT I efficiently acts on all substrates having a terminal beta-linked GlcNAc, beta4-GalT V appeared to be far more restricted in acceptor usage. Beta4-GalT V acts with high preference on acceptors that contain the GlcNAc beta1-->6GalNAc structural element, as found in O-linked core 2-, 4- and 6-based glycans, but not on substrates related to V-linked or blood group I-active oligosaccharides. These results suggest that beta4-GalT V may function in the synthesis of lacNAc units on O-linked chains, particularly in tissues which do not express beta4-GalT I, such as brain.

Baculoviridae↗
PubMedDate not supplied

Potential functional foods in the traditional Maori diet.

The Maori people were early New Zealand settlers of Polynesian descent. The incidence of non-infectious diseases appears to have been low in these people, perhaps in part due to the presence of protective chemical constituents within their food plant supply. Three of the tropical crops they introduced are still eaten here today: the sweet potato or kumara (Ipomoea batatas), the taro (Colocasia esculenta) and the cabbage tree or ti (Cordyline terminalis). Sporamins A and B, the major storage proteins of kumara tubers, act as proteinase inhibitors, and may have other anti-cancer properties. The tubers also contain the anti-coagulant coumarins, scopoletin, aesculetin, and umbelliferone. The corms of taro contain the anthocyanins, cyanidin 3-glucoside, pelargonidin 3-glucoside and cyanidin 3-rhamnoside, reported to have antioxidant and anti-inflammatory properties. Anthocyanins are also major components of a so-called "Maori potato", a variety officially known as Ureniki, which has a purple skin and flesh and was widely eaten in the early 1900s. Anthocyanins are also present in ripe berries of the ramarama (Lophomyrtus bullata) and rohutu (Neomyrtus pedunculata). Both the leaves and seeds of the introduced cabbage tree (Cordyline terminalis) and the native Cordyline spp., C. australis, C. indivisa, and C. pumilo, were eaten. The seeds of C. australis, of some Astelia spp., and of hinau (Elaeocarpus dentatus) are good sources of various essential fatty acids, generally regarded as protective against cardiovascular disease. Shoots and leaves from a wide range of native species were traditionally eaten as greens, especially "sow thistle" or puha (Sonchus spp.), reportedly high in Vitamin C and various phenolics. "New Zealand spinach" (Tetragonia tetragonioides or T. expansa) has anti-ulcerogenic activity that has been traced to two cerebrosides and anti-inflammatory activity that has been traced to novel water-soluble polysaccharides, as well as antioxidant phenylpropanoids including caffeic acid. Leaves of the "hen and chickens" fern (Asplenium bulbiferum) contain antioxidant flavonoids such as kaempferol glucosides. Native seaweeds also have useful nutritive properties.

Antioxidants↗
PubMed1998

Oscillations in peroxidase-catalyzed reactions and their potential function in vivo.

The peroxidase-oxidase reaction has become a model system for the study of oscillations and complex dynamics in biochemical systems. In the present paper we give an overview of previous experimental and theoretical studies of the peroxidase-oxidase reaction. Recent in vitro experiments have raised the question whether the reaction also exhibits oscillations and complex dynamics in vivo. To investigate this possibility further we have undertaken new experimental studies of the reaction, using horseradish extracts and phenols which are widely distributed in plants. The results are discussed in light of the occurrence and a possible functional role of oscillations and complex dynamics of the peroxidase-oxidase reaction in vivo.

Journal Article↗
PubMed1991

Inhibition of cytokine function: potential in autoimmune disease.

Multiple lines of evidence implicate cytokines in the pathogenesis of autoimmune and inflammatory diseases. Neutralization of the biological activities of cytokines by interfering with ligand binding to specific cell-surface cytokine receptors thus represents an approach to controlling such diseases. Several agents, including novel, receptor-based antagonists, are being developed and tested in disease models.

Animals↗
PubMed2004

Structure of human apolipoprotein A-IV: a distinct domain architecture among exchangeable apolipoproteins with potential functional implications.

Apolipoprotein A-IV (apoA-IV) is an exchangeable apolipoprotein that shares many functional similarities with related apolipoproteins such as apoE and apoA-I but has also been implicated as a circulating satiety factor. However, despite the fact that it contains many predicted amphipathic alpha-helical domains, relatively little is known about its tertiary structure. We hypothesized that apoA-IV exhibits a characteristic functional domain organization that has been proposed to define apoE and apoA-I. To test this, we created truncation mutants in a bacterial system that deleted amino acids from either the N- or C-terminal ends of human apoA-IV. We found that apoA-IV was less stable than apoA-I but was more highly organized in terms of its cooperativity of unfolding. Deletion of the extreme N and C termini of apoA-IV did not significantly affect the cooperativity of unfolding, but deletions past amino acid 333 on the C terminus or amino acid 61 on the N terminus had major destabilizing effects. Functionally, apoA-IV was less efficient than apoA-I at clearing multilamellar phospholipid liposomes and promoting ATP-binding cassette transporter A1-mediated cholesterol efflux. However, deletion of a C-terminal region of apoA-IV, which is devoid of predicted amphipathic alpha helices (amino acids 333-376) stimulated both of these activities dramatically. We conclude that the amphipathic alpha helices in apoA-IV form a single, large domain that may be similar to the N-terminal helical bundle domains of apoA-I and apoE but that apoA-IV lacks the C-terminal lipid-binding and cholesterol efflux-promoting domain present in these apolipoproteins. In fact, the C terminus of apoA-IV appears to reduce the ability of apoA-IV to interact with lipids and promote cholesterol efflux. This indicates that, although apoA-IV may have evolved from gene duplication events of ancestral apolipoproteins and shares the basic amphipathic helical building blocks, the overall localization of functional domains within the sequence is quite different from apoA-I and apoE.

ATP-Binding Cassette Transporters↗
PubMed2005

Organization and potential function of the mrjp3 locus in four honeybee species.

Royal jelly is a nutritious secretion produced by nurse honeybees to provision queens and growing larvae. Major proteins of royal jelly are mutually similar, and they all belong to the MRJP/yellow protein family (pfam03022). The mrjp3 loci in four traditional honeybee species (Apis mellifera, Apis cerana,Apis dorsata, and Apis florea) were sequenced and found to share high sequence and structural similarities. PCR analyses confirmed the presence of an extensive repetitive region, which showed size and sequence polymorphisms in all species. The evolutionary history of mrjp genes and their repetitive regions was reconstructed from their nucleotide sequences. The analyses proved that the repeat region appeared early in the evolution of the mrjp gene family and that the extreme elongation of the repeat is mrjp3 specific. In the MRJPs was documented a correlation between nitrogen content and repeat length. Therefore, it is argued that the repeat occurred due to a selection for an increase in nitrogen storage for a more efficient nutrition of queens and larvae.

Amino Acid Sequence↗
PubMed2002

Role of the autoimmune regulator (AIRE) gene in alopecia areata: strong association of a potentially functional AIRE polymorphism with alopecia universalis.

Alopecia areata is characterized by a reversible form of patchy or complete hair loss associated with T-cell infiltration of hair follicles. The lifetime disease risk of approximately 1.4% in the general population is increased to more than 30% in autoimmune polyendocrinopathy candidiasis ectodermal dysplasia syndrome (APECED), a recessive condition resulting from a mutation of the autoimmune regulator (AIRE) gene on chromosome 21q22.3. Aire protein is thought to have transcriptional regulatory activity but its role is not well defined at present. In this study, we have examined the possible involvement of AIRE in the pathogenesis of alopecia areata. On screening the AIRE coding sequence, we identified 20 variants. Two of these at positions, G961C and T1029C, give rise to amino acid changes, S278R and V301A, located in the DNA-binding segment (SAND) and PHD1 zinc finger motif, respectively. We found no difference in the frequency of the AIRE T1029C polymorphism between the control and patient groups. We genotyped 202 alopecia areata patients and 175 matched Caucasian controls for the AIRE G961C alleles. The frequency of the rare allele (961G) was 0.08 in the controls and there was a significant increase to 0.13 in alopecia areata overall and 0.20 in severe disease (alopecia universalis). We found no association between the AIRE G961G variant and mild (patchy) alopecia areata or alopecia totalis. However, the AIRE 961G allele is a potent risk factor (> 3) for the severest form of alopecia areata, and for disease of early age at onset (at 30 years). The change from serine to arginine in the SAND domain of AIRE protein may have a significant effect on AIRE DNA-binding activity. Moreover, our results could provide a rational explanation of the unusually high frequency of AA in APECED patients, supporting the concept of AA as an autoimmune disease.

Adolescent↗
PubMed2006

Butyrate modulates TGF-beta1 generation and function: potential renal benefit for Acacia(sen) SUPERGUM (gum arabic)?

Anecdotal evidence suggests that high fibre supplementation of dietary intake may have health benefits in renal disease related to alterations in circulating levels of short-chain fatty acids. The aim of the study was to examine the hypothesis that dietary manipulation may increase serum butyrate and thus have potential beneficial effects in renal disease. We examined the effect of dietary supplementation with a gum arabic sample of standardized molecular characteristics, Acacia(sen) SUPERGUM EM2 (SUPERGUM), on systemic levels of butyrate in normal human subjects. In an in vitro study, we also examined the potential role of butyrate in modifying the generation of the profibrotic cytokine transforming growth factor-beta (TGF-beta1) by renal epithelial cells. Following 8 weeks of dietary supplementation with 25 g/day of SUPERGUM, there was a two-fold increase in serum butyrate (n=7, P=0.03). In vitro work demonstrated that exposure of renal epithelial cells to elevated concentrations of butyrate suppressed both basal and stimulated TGF-beta1 synthesis. The action of butyrate was mediated by suppression of the extracellular signal-regulated kinase/mitogen-activated protein kinase signalling pathway. In addition, butyrate exposures reduced the response of renal epithelial cells to TGF-beta1 as assessed by luciferase activity of a TGF-beta-responsive reporter construct. Attenuation of TGF-beta1 signalling was associated with reduced phosphorylation of Smad 3 and decreased trafficking of TGF-beta1 receptors into signalling, non-lipid raft-associated membrane fractions. In conclusion, the data demonstrate that dietary supplementation with SUPERGU increased serum butyrate, which at least in vitro has beneficial effects on renal pro-fibrotic cytokine generation.

Butyrates↗
PubMed2004

The potential function of steroid sulphatase activity in steroid production and steroidogenic acute regulatory protein expression.

The first step in the biosynthesis of steroid hormones is conversion of cholesterol into pregnenolone. StAR (steroidogenic acute regulatory) protein plays a crucial role in the intra-mitochondrial movement of cholesterol. STS (steroid sulphatase), which is present ubiquitously in mammalian tissues, including the placenta, adrenal gland, testis and ovary, desulphates a number of 3beta-hydroxysteroid sulphates, including cholesterol sulphate. The present study was designed to examine the effect of STS on StAR protein synthesis and steroidogenesis in cells. Steroidogenic activities of COS-1 cells that had been co-transfected with a vector for the cholesterol P450scc (cytochrome P450 side-chain-cleavage enzyme) system, named F2, a StAR expression vector (pStAR), and an STS expression vector (pSTS) were assayed. Whole-cell extracts were subjected to SDS/PAGE and then to Western blot analysis. pSTS co-expressed in COS-1 cells with F2 and pStAR increased pregnenolone synthesis 2-fold compared with that of co-expression with F2 and pStAR. Western blot analysis using COS-1 cells that had been co-transfected with pSTS, F2 and pStAR revealed that StAR protein levels increased, whereas STS and P450scc protein levels did not change. The amount of StAR protein translation products increased when pSTS was added to an in vitro transcription-translation reaction mixture. Pulse-chase experiments demonstrated that the 37 kDa StAR pre-protein disappeared significantly ( P <0.01) more slowly in COS-1 cells that had been transfected with pSTS than in COS-1 cells that had not been transfected with pSTS. The increase in StAR protein level is not a result of an increase in StAR gene expression, but is a result of both an increase in translation and a longer half-life of the 37 kDa pre-StAR protein. In conclusion, STS increases StAR protein expression level and stimulates steroid production.

Animals↗
PubMed1996

Molecular cloning, expression and potential functions of the human proteinase-activated receptor-2.

We used PCR to amplify proteinase activated receptor-2 (PAR-2) from human kidney cDNA. The open reading frame comprised 1191 bp and encoded a protein of 397 residues with 83% identity with mouse PAR-2. In KNRK cells (a line of kirsten murine sarcoma virus-transformed rat kidney epithelial cells) transfected with this cDNA, trypsin and activating peptide (AP) corresponding to the tethered ligand exposed by trypsin cleavage (SLIGKV-NH2) induced a prompt increase in cytosolic calcium ion concentration ([Ca2+]i). Human PAR-2 (hPAR-2) resided both on the plasma membrane and in the Golgi apparatus. hPAR-2 mRNA was highly expressed in human pancreas, kidney, colon, liver and small intestine, and by A549 lung and SW480 colon adenocarcinoma cells. Hybridization in situ revealed high expression in intestinal epithelial cells throughout the gut. Trypsin and AP stimulated an increase in [Ca2+]i in a rat intestinal epithelial cell line (hBRIE 380) and stimulated amylase secretion in isolated pancreatic acini. In A549 cells, which also responded to trypsin and AP with mobilization of cytosolic Ca2+, AP inhibited colony formation. Thus PAR-2 may serve as a trypsin sensor in the gut. Its expression by cells and tissues not normally exposed to pancreatic trypsin suggests that other proteases could serve as physiological activators.

Adenocarcinoma↗
PubMed2000

HLA-G in the human placenta: expression and potential functions.

HLA-G is a non-classical class I molecule specifically expressed in the placenta, suggesting that it might have a physiological function at the materno-foetal interface. The structural characteristics of HLA-G, the placental pattern of expression and the functional properties of this class Ib glycoprotein in vitro are described and evaluated in the context of pregnancy. The possible anti-viral function of HLA-G, its modulatory role of natural killer cell activity and its likely non-immunological functions are discussed.

Animals↗
PubMed2000

Expression of 15 glutamate receptor subunits and various splice variants in tissue slices and single neurons of brainstem nuclei and potential functional implications.

Brainstem nuclei serve a diverse array of functions in many of which ionotropic glutamate receptors are known to be involved. However, little detailed information is available on the expression of different glutamate receptor subunits in specific nuclei. We used RT-PCR in mice to analyze the glutamate receptor subunit composition of the pre-Bötzinger complex, the hypoglossal nucleus, the nucleus of the solitary tract, and the inferior olive. Analyzing 15 receptor subunits and five variants, we found all four alpha-amino-3-hydroxy-5-methyl-4-propionic acid (AMPA) and six NMDA receptor (NR) subunits as well as three of five kainate (KA) receptors (GluR5, GluR6, and KA1) to be expressed in all nuclei. However, some distinct differences were observed: The inferior olive preferentially expresses flop variants of AMPA receptors, GluR7 is more abundant in the pre-Bötzinger complex than in the other nuclei, and NR2C is most prominent in the nucleus of the solitary tract. In single hypoglossal motoneurons and interneurons of the pre-Bötzinger complex investigation of GluR2 editing revealed strong expression of the GluR2-R editing variant, suggesting low Ca2+ permeability of AMPA receptors. Thus, Ca2+-permeable AMPA receptors are unlikely to be the cause for the reported selective vulnerability of hypoglossal motoneurons during excitotoxic events.

Alternative Splicing↗