scholarly journals Association Between the Rat Homologue of CO-029, a Metastasis-associated Tetraspanin Molecule and Consumption Coagulopathy

1998 ◽  
Vol 141 (1) ◽  
pp. 267-280 ◽  
Author(s):  
Christoph Claas ◽  
Simone Seiter ◽  
Andreas Claas ◽  
Larissa Savelyeva ◽  
Manfred Schwab ◽  
...  
Keyword(s):  
Amino Acids ◽  
Monoclonal Antibody ◽  
Amino Acid ◽  
Functional Role ◽  
Human Tumor ◽  
Tumor Cell Line ◽  
Metastatic Potential ◽  
Massive Bleeding ◽  
Consumption Coagulopathy

Recently, we have described a panel of metastasis-associated antigens in the rat, i.e., of molecules expressed on metastasizing, but not on nonmetastasizing tumor lines. One of these molecules, recognized by the monoclonal antibody D6.1 and named accordingly D6.1A, was found to be abundantly expressed predominantly on mesenchyme-derived cells. The DNA of the antigen has been isolated and cloned. Surprisingly, the gene product proved to interfere strongly with coagulation. The 1.182-kb cDNA codes for a 235–amino acid long molecule with a 74.2% homology in the nucleotide and a 70% homology in the amino acid sequence to CO-029, a human tumor-associated molecule. According to the distribution of hydrophobic and hydrophilic amino acids, D6.1A belongs to the tetraspanin superfamily. Western blotting of D6.1A-positive metastasizing tumor lines revealed that the D6.1A, like many tetraspanin molecules, is linked to further membrane molecules, one of which could be identified as α6β1 integrin. Transfection of a low-metastasizing tumor cell line with D6.1A cDNA resulted in increased metastatic potential and provided a clue as to the functional role of D6.1A. We noted massive bleeding around the metastases and, possibly as a consequence, local infarctions predominantly in the mesenteric region and all signs of a consumption coagulopathy. By application of the D6.1 antibody the coagulopathy was counterregulated, though not prevented. It has been known for many years that tumor growth and progression is frequently accompanied by thrombotic disorders. Our data suggest that the phenomenon could well be associated with the expression of tetraspanin molecules.

scholarly journals 45 Opportunity with functional role of supplemental amino acids

2019 ◽  
Vol 97 (Supplement_2) ◽  
pp. 24-24
Author(s):  
Yanbin Shen ◽  
Sung Woo Kim
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Social Stress ◽  
Functional Role ◽  
Building Blocks ◽  
Animal Production ◽  
The Body ◽  
Technological Advancement ◽  
Crystalline Amino Acids

Abstract The technological advancement in production of crystalline amino acids has driven the cost of crystalline amino acids down significantly and facilitated the wide use of crystalline amino acids in food animal production. The primary reason of use of crystalline amino acids in am animal’s diet is to provide dietary essential nutrients for protein synthesis and to balance the diet and reduce dietary cost. Extensive researches with amino acids have greatly enabled such use. As a result, most swine diets today are formulated with 3 or 4 supplemental amino acids. However, the economical return on including beyond 4 supplemental amino acids becomes low and thus discourages the use of more than 4 supplemental amino acids for dietary saving purpose. The use of the functional role of amino acids might bear the new opportunity for amino acids. Tryptophan has unique physiological functions involving synthesize serotonin in the body. Increasing tryptophan intake is shown to elevate serotonin synthesis in the brain of pigs and reduce stress and improve performance of pigs under social stress. Research shows that methionine is used as a precursor of glutathione to protect intestinal mucosa from oxidative damages during weaning stress. Arginine, glutamine, and glutamate are shown to have functions in cell proliferation, potentially improving intestinal and immune function of nursery pigs and preventing loss of lean body mass in the sow. Leucine is a ketogenic amino acid. The carbon skeleton of leucine is converted to acetylCoA, which could be used for fatty acid synthesis in muscle tissue. Research showed that intramuscular fat was increased by feeding high dietary leucine levels. Overall, the different functions of individual AA beyond their roles as the building blocks for proteins give additional opportunities of amino acid application in animal production.

10 THE ROLE OF DIETARY L-SERINE IN THE REGULATION OF INTESTINAL MUCUS BARRIER DURING INFLAMMATION

2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S42-S42
Author(s):  
Kohei Sugihara ◽  
Nobuhiko Kamada
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Gut Microbiota ◽  
Control Diet ◽  
Bacterial Strains ◽  
Germ Free ◽  
Intestinal Mucus ◽  
Gnotobiotic Mice ◽  
Mucus Barrier

Abstract Background Recent accumulating evidence suggests that amino acids have crucial roles in the maintenance of intestinal homeostasis. In inflammatory bowel disease (IBD), amino acid metabolism is changed in both host and the gut microbiota. Among amino acids, L-serine plays a central role in several metabolic processes that are essential for the growth and survival of both mammalian and bacterial cells. However, the role of L-serine in intestinal homeostasis and IBD remains incompletely understood. In this study, we investigated the effect of dietary L-serine on intestinal inflammation in a murine model of colitis. Methods Specific pathogen-free (SPF) mice were fed either a control diet (amino acid-based diet) or an L-serine-deficient diet (SDD). Colitis was induced by the treatment of dextran sodium sulfate (DSS). The gut microbiome was analyzed by 16S rRNA sequencing. We also evaluate the effect of dietary L-serine in germ-free mice and gnotobiotic mice that were colonized by a consortium of non-mucolytic bacterial strains or the consortium plus mucolytic bacterial strains. Results We found that the SDD exacerbated experimental colitis in SPF mice. However, the severity of colitis in SDD-fed mice was comparable to control diet-fed mice in germ-free condition, suggesting that the gut microbiota is required for exacerbation of colitis caused by the restriction of dietary L-serine. The gut microbiome analysis revealed that dietary L-serine restriction fosters the blooms of a mucus-degrading bacterium Akkermansia muciniphila and adherent-invasive Escherichia coli in the inflamed gut. Consistent with the expansion of mucolytic bacteria, SDD-fed mice showed a loss of the intestinal mucus layer. Dysfunction of the mucus barrier resulted in increased intestinal permeability, thereby leading to bacterial translocation to the intestinal mucosa, which subsequently increased the severity of colitis. The increased intestinal permeability and subsequent bacterial translocation were observed in SDD-fed gnotobiotic mice that colonized by mucolytic bacteria. In contrast, dietary L-serine restriction did not alter intestinal barrier integrity in gnotobiotic mice that colonized only by non-mucolytic bacteria. Conclusion Our results suggest that dietary L-serine regulates the integrity of the intestinal mucus barrier during inflammation by limiting the expansion of mucus degrading bacteria.

scholarly journals Biological role of D-amino acid oxidase and D-aspartate oxidase. Effects of D-amino acids.

1993 ◽  
Vol 268 (36) ◽  
pp. 26941-26949
Author(s):  
A D'Aniello ◽  
G D'Onofrio ◽  
M Pischetola ◽  
G D'Aniello ◽  
A Vetere ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Biological Role ◽  
Acid Oxidase ◽  
Amino Acid Oxidase

scholarly journals Roles of the C-Terminal Amino Acids of Non-Hexameric Helicases: Insights from Escherichia coli UvrD

2021 ◽  
Vol 22 (3) ◽  
pp. 1018
Author(s):  
Hiroaki Yokota
Keyword(s):  
Escherichia Coli ◽  
Amino Acids ◽  
Amino Acid ◽  
Single Molecule ◽  
Underlying Mechanism ◽  
Amino Acid Sequences ◽  
E Coli ◽  
X Ray Crystallography ◽  
Terminal Amino

Helicases are nucleic acid-unwinding enzymes that are involved in the maintenance of genome integrity. Several parts of the amino acid sequences of helicases are very similar, and these quite well-conserved amino acid sequences are termed “helicase motifs”. Previous studies by X-ray crystallography and single-molecule measurements have suggested a common underlying mechanism for their function. These studies indicate the role of the helicase motifs in unwinding nucleic acids. In contrast, the sequence and length of the C-terminal amino acids of helicases are highly variable. In this paper, I review past and recent studies that proposed helicase mechanisms and studies that investigated the roles of the C-terminal amino acids on helicase and dimerization activities, primarily on the non-hexermeric Escherichia coli (E. coli) UvrD helicase. Then, I center on my recent study of single-molecule direct visualization of a UvrD mutant lacking the C-terminal 40 amino acids (UvrDΔ40C) used in studies proposing the monomer helicase model. The study demonstrated that multiple UvrDΔ40C molecules jointly participated in DNA unwinding, presumably by forming an oligomer. Thus, the single-molecule observation addressed how the C-terminal amino acids affect the number of helicases bound to DNA, oligomerization, and unwinding activity, which can be applied to other helicases.

scholarly journals BIOSYNTHESIS IN ISOLATED ACETABULARIA CHLOROPLASTS

1972 ◽  
Vol 54 (2) ◽  
pp. 279-294 ◽  
Author(s):  
David C. Shephard ◽  
Wendy B. Levin
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Technical Problems ◽  
Hydrolyzed Protein ◽  
Protein Amino Acids ◽  
Amino Acid Labeling ◽  
Labeling Pattern

The ability of chloroplasts isolated from Acetabulana mediterranea to synthesize the protein amino acids has been investigated. When this chloroplast isolate was presented with 14CO2 for periods of 6–8 hr, tracer was found in essentially all amino acid species of their hydrolyzed protein Phenylalanine labeling was not detected, probably due to technical problems, and hydroxyproline labeling was not tested for The incorporation of 14CO2 into the amino acids is driven by light and, as indicated by the amount of radioactivity lost during ninhydrin decarboxylation on the chromatograms, the amino acids appear to be uniformly labeled. The amino acid labeling pattern of the isolate is similar to that found in plastids labeled with 14CO2 in vivo. The chloroplast isolate did not utilize detectable amounts of externally supplied amino acids in light or, with added adenosine triphosphate (ATP), in darkness. It is concluded that these chloroplasts are a tight cytoplasmic compartment that is independent in supplying the amino acids used for its own protein synthesis. These results are discussed in terms of the role of contaminants in the observed synthesis, the "normalcy" of Acetabularia chloroplasts, the synthetic pathways for amino acids in plastids, and the implications of these observations for cell compartmentation and chloroplast autonomy.

scholarly journals Regulatory Role of the Morbillivirus Attachment Protein Head-to-Stalk Linker Module in Membrane Fusion Triggering

2018 ◽  
Vol 92 (18) ◽  
Author(s):  
Michael Herren ◽  
Neeta Shrestha ◽  
Marianne Wyss ◽  
Andreas Zurbriggen ◽  
Philippe Plattet
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Cell Surface ◽  
Membrane Fusion ◽  
Measles Virus ◽  
Cell Entry ◽  
Regulatory Role ◽  
Fusion Activity ◽  
Animal Pathogens

ABSTRACTMorbillivirus (e.g., measles virus [MeV] and canine distemper virus [CDV]) host cell entry is coordinated by two interacting envelope glycoproteins, namely, an attachment (H) protein and a fusion (F) protein. The ectodomain of H proteins consists of stalk, connector, and head domains that assemble into functional noncovalent dimer-of-dimers. The role of the C-terminal module of the H-stalk domain (termed linker) and the connector, although putatively able to assume flexible structures and allow receptor-induced structural rearrangements, remains largely unexplored. Here, we carried out a nonconservative mutagenesis scan analysis of the MeV and CDV H-linker/connector domains. Our data demonstrated that replacing isoleucine 146 in H-linker (H-I146) with any charged amino acids prevented virus-mediated membrane fusion activity, despite proper trafficking of the mutants to the cell surface and preserved binding efficiency to the SLAM/CD150 receptor. Nondenaturing electrophoresis revealed that these charged amino acid changes led to the formation of irregular covalent H tetramers rather than functional dimer-of-dimers formed when isoleucine or other hydrophobic amino acids were present at residue position 146. Remarkably, we next demonstrated that covalent H tetramerizationper sewas not the only mechanism preventing F activation. Indeed, the neutral glycine mutant (H-I146G), which exhibited strong covalent tetramerization propensity, maintained limited fusion promotion activity. Conversely, charged H-I146 mutants, which additionally carried alanine substitution of natural cysteines (H-C139A and H-C154A) and thus were unable to form covalently linked tetramers, were fusion activation defective. Our data suggest a dual regulatory role of the hydrophobic residue at position 146 of the morbillivirus head-to-stalk H-linker module: securing the assembly of productive dimer-of-dimers and contributing to receptor-induced F-triggering activity.IMPORTANCEMeV and CDV remain important human and animal pathogens. Development of antivirals may significantly support current global vaccination campaigns. Cell entry is orchestrated by two interacting glycoproteins (H and F). The current hypothesis postulates that tetrameric H ectodomains (composed of stalk, connector, and head domains) undergo receptor-induced rearrangements to productively trigger F; these conformational changes may be regulated by the H-stalk C-terminal module (linker) and the following connector domain. Mutagenesis scan analysis of both microdomains revealed that replacing amino acid 146 in the H-linker region with nonhydrophobic residues produced covalent H tetramers which were compromised in triggering membrane fusion activity. However, these mutant proteins retained their ability to traffic to the cell surface and to bind to the virus receptor. These data suggest that the morbillivirus linker module contributes to the folding of functional pre-F-triggering H tetramers. Furthermore, such structures might be critical to convert receptor engagement into F activation.

Major Compatible Solutes and Structural Adaptation of Proteins in Extremophiles

2022 ◽  
pp. 161-186
Author(s):  
Hardik Shah ◽  
Khushbu Panchal ◽  
Amisha Panchal
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Osmotic Stress ◽  
Amino Acid Composition ◽  
Scientific Community ◽  
Compatible Solutes ◽  
Organic Solutes ◽  
Structural Adaptation ◽  
Extreme Habitats

Extremophiles are the most ancient microbes on the Earth and also a center of attraction for the scientific community for research because of their ability to adapt to extreme habitats. Compatible solutes are among those factors which enable these microorganisms to thrive in such extreme habitats. Under osmotic stress, the majority of extremophiles accumulate specific organic solutes such as amino acids, sugars, polyols, and their derivatives. In addition, proteins in extremophiles are found to be evolved by changing their amino acid composition to alter the hydrophobicity of its core and surface charge to maintain activity. This chapter encompasses a comprehensive study about the role of various compatible solutes in the endurance of microorganisms under extremophilic conditions, synthesis of compatible solutes, nature of extremophilic proteins, and their applications. Furthermore, an attempt has been made to cover various strategies adopted by the scientific community while pursuing research on compatible solutes.

Role of the gamma-glutamyl cycle in the regulation of amino acid translocation

1989 ◽  
Vol 257 (6) ◽  
pp. E916-E922 ◽  
Author(s):  
J. R. Vina ◽  
M. Palacin ◽  
I. R. Puertes ◽  
R. Hernandez ◽  
J. Vina
Keyword(s):  
Amino Acids ◽  
Mammary Gland ◽  
Amino Acid ◽  
Amino Acid Transport ◽  
Acid Transport ◽  
Pregnant Rats ◽  
Gamma Glutamyl ◽  
Extracellular Signals ◽  
Previously Treated

Amino acid translocation was studied in the mammary gland of lactating rats and in the placenta of pregnant rats. The uptake of amino acids by the mammary gland is maximal on days 10-14 of lactation and is minimal on days 19-21. However, on day 19 maximal uptake can be restored by injection of 1) small amounts of gamma-glutamyl amino acids, 2) 5-oxoproline, and 3) an inhibitor of 5-oxoprolinase. A severe decrease in uptake of amino acids at the peak of lactation is provoked by anthglutin, an inhibitor of gamma-glutamyltranspeptidase (GGT). Simultaneous injection of 5-oxoproline blocks these effects of anthglutin. In pregnant rats, inhibition (79%) of placental GGT activity by acivicin results in a 50% decrease of placental L-[U-14C]-alanine transfer and 70-80% decrease in its incorporation into the placental and fetal proteins. Infusion of 5-oxoproline to mothers previously treated with acivicin restored the L-[U-14C]-alanine transfer. Acivicin or 5-oxoproline did not modify the transfer and metabolism of D-[U14C]glucose by the fetal placental unit. These results show that the gamma-glutamyl cycle should not be considered a mechanism for amino acid transport but rather a generator of extracellular signals, gamma-glutamyl amino acids, that are converted intracellularly to 5-oxoproline, which activates uptake and/or metabolism of amino acids.

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