Publications by authors named "Dagmar Heydeck"

Eicosanoids and related compounds are pleiotropic lipid mediators, which play a role in cell differentiation and in the pathogenesis of various diseases. The biosynthesis of these lipids has extensively been studied in highly developed mammals including humans but little is known about the formation of these mediators in more ancient Prototheria. We searched the genomes of two extant prototherian species (platypus, short-beaked echidna) for genes encoding for lipoxygenase- (ALOX) and prostaglandin synthase-isoforms (PTGS) and detected intact single copy genes for ALOX5, ALOX12, ALOX12B, ALOXE3, PTGS1 and PTGS2.

View Article and Find Full Text PDF

Arachidonic acid 15-lipoxygenases (ALOX15) play a role in mammalian erythropoiesis but they have also been implicated in inflammatory processes. Seven intact Alox genes have been detected in the mouse reference genome and the mouse Alox15 gene is structurally similar to the orthologous genes of other mammals. However, mouse and human ALOX15 orthologs have different functional characteristics.

View Article and Find Full Text PDF

The human genome involves six functional arachidonic acid lipoxygenase () genes and the corresponding enzymes (ALOX15, ALOX15B, ALOX12, ALOX12B, ALOXE3, ALOX5) have been implicated in cell differentiation and in the pathogenesis of inflammatory, hyperproliferative, metabolic, and neurological disorders. In other vertebrates, ALOX-isoforms have also been identified, but they occur less frequently. Since bony fish represent the most abundant subclass of vertebrates, we recently expressed and characterized putative ALOX15 orthologs of three different bony fish species (, , ).

View Article and Find Full Text PDF

Background, Objectives And Design: Arachidonic acid 15-lipoxygenase (ALOX15) has been implicated in the pathogenesis of inflammatory diseases but since pro- and anti-inflammatory roles have been suggested, the precise function of this enzyme is still a matter of discussion. To contribute to this discussion, we created transgenic mice, which express human ALOX15 under the control of the activating protein 2 promoter (aP2-ALOX15 mice) and compared the sensitivity of these gain-of-function animals in two independent mouse inflammation models with Alox15-deficient mice (loss-of-function animals) and wildtype control animals.

Materials And Methods: Transgenic aP2-ALOX15 mice were tested in comparison with Alox15 knockout mice (Alox15) and corresponding wildtype control animals (C57BL/6J) in the complete Freund's adjuvant induced hind-paw edema model and in the dextran sulfate sodium induced colitis (DSS-colitis) model.

View Article and Find Full Text PDF

Mammalian arachidonic acid lipoxygenases (ALOXs) have been implicated in the pathogenesis of inflammatory diseases, and its pro- and anti-inflammatory effects have been reported for different ALOX-isoforms. Human ALOX15B oxygenates arachidonic acid to its 15-hydroperoxy derivative, whereas the corresponding 8-hydroperoxide is formed by mouse Alox15b (Alox8). This functional difference impacts the biosynthetic capacity of the two enzymes for creating pro- and anti-inflammatory eicosanoids.

View Article and Find Full Text PDF

Arachidonic acid lipoxygenases (ALOX) have been implicated in the pathogenesis of inflammatory, hyperproliferative, neurodegenerative, and metabolic diseases, but the physiological function of ALOX15 still remains a matter of discussion. To contribute to this discussion, we created transgenic mice (aP2-ALOX15 mice) expressing human ALOX15 under the control of the aP2 (adipocyte fatty acid binding protein 2) promoter, which directs expression of the transgene to mesenchymal cells. Fluorescence in situ hybridization and whole-genome sequencing indicated transgene insertion into the E1-2 region of chromosome 2.

View Article and Find Full Text PDF

Eicosanoids and related compounds are pleiotropic lipid mediators, which are biosynthesized in mammals via three distinct metabolic pathways (cyclooxygenase pathway, lipoxygenase pathway, epoxygenase pathway). These mediators have been implicated in the pathogenesis of inflammatory diseases and drugs interfering with eicosanoid signaling are currently available as antiphlogistics. Eicosanoid biosynthesis has well been explored in mammals including men, but much less detailed information is currently available on eicosanoid biosynthesis in other vertebrates including bony fish.

View Article and Find Full Text PDF

The guanine-rich RNA sequence binding factor 1 (GRSF1) is an RNA-binding protein of the heterogenous nuclear ribonucleoprotein H/F (hnRNP H/F) family that binds to guanine-rich RNA sequences forming G-quadruplex structures. In mice and humans there are single copy GRSF1 genes, but multiple transcripts have been reported. GRSF1 has been implicated in a number of physiological processes (e.

View Article and Find Full Text PDF

Mammalian arachidonic acid lipoxygenases (ALOXs) have been implicated in cell differentiation and in the pathogenesis of inflammation. The mouse genome involves seven functional genes and the encoded enzymes share a high degree of amino acid conservation with their human orthologs. There are, however, functional differences between mouse and human ALOX orthologs.

View Article and Find Full Text PDF

Arachidonic acid lipoxygenases (ALOXs) have been implicated in the immune response of mammals. The reaction specificity of these enzymes is decisive for their biological functions and ALOX classification is based on this enzyme property. Comparing the amino acid sequences and the functional properties of selected mammalian ALOX15 orthologs we previously hypothesized that the reaction specificity of these enzymes can be predicted based on their amino acid sequences (Triad Concept) and that mammals, which are ranked in evolution below gibbons, express arachidonic acid 12-lipoxygenating ALOX15 orthologs.

View Article and Find Full Text PDF

Lipoxygenases (ALOX-isoforms) are lipid peroxidizing enzymes, which have been implicated in cell differentiation and maturation but also in the biosynthesis of lipid mediators playing important roles in the pathogenesis of inflammatory, hyperproliferative and neurological diseases. In mammals these enzymes are widely distributed and the human genome involves six functional genes encoding for six distinct human ALOX paralogs. In mice, there is an orthologous enzyme for each human ALOX paralog but the catalytic properties of human and mouse ALOX orthologs show remarkable differences.

View Article and Find Full Text PDF

Arachidonic acid 5-lipoxygenase (ALOX5) is the key enzyme in the biosynthesis of pro-inflammatory leukotrienes. We recently created knock-in mice (-KI) which express an arachidonic acid 15-lipoxygenating Alox5 mutant instead of the 5-lipoxygenating wildtype enzyme. These mice were leukotriene deficient but exhibited an elevated linoleic acid oxygenase activity.

View Article and Find Full Text PDF

Endocannabinoids, such as anandamide (ANA) and 2-arachidonoylglycerol (2AG), are lipid-signaling molecules that can be oxidized by lipid-peroxidizing enzymes, and this oxidation alters the bioactivity of these lipid mediators. Here, under strictly comparable experimental conditions, we explored whether ANA and 2AG function as substrates for four human (ALOX15, ALOX15B, ALOX12, ALOX5) and three mice Alox isoforms (Alox15, Alox12, Alox5) and compared the rates of product formation with those of arachidonic acid oxygenation. Except for ALOX5, the two endocannabinoids were more efficiently oxygenated than arachidonic acid by human ALOX isoforms.

View Article and Find Full Text PDF

Background: The guanine-rich RNA sequence binding factor 1 (GRSF1) is an RNA-binding protein of the hnRNP H/F family, which has been implicated in erythropoiesis, regulation of the redox homeostasis, embryonic brain development, mitochondrial function and cellular senescence. The molecular basis for GRSF1-RNA interaction has extensively been studied in the past but for the time being GRSF1 binding proteins have not been identified.

Methods: To search for GRSF1 binding proteins we first employed the yeast two-hybrid system and screened a cDNA library of human fetal brain for potential GRSF1 binding proteins.

View Article and Find Full Text PDF

After 300 million years of evolution, the first land-living mammals reentered the marine environment some 50 million years ago. The driving forces for this dramatic lifestyle change are still a matter of discussion but the struggle for food resources and the opportunity to escape predators probably contributed. Reentering the oceans requires metabolic adaption putting evolutionary pressure on a number of genes.

View Article and Find Full Text PDF

His596 of human ALOX12 has been suggested to interact with the COO-group of arachidonic acid during ALOX catalysis. In mammalian ALOX15 orthologs Gln596 occupies this position and this amino acid exchange might contribute to the functional differences between the two ALOX-isoforms. To explore the role of Gln596 for ALOX15 functionality we mutated this amino acid to different residues in rabbit and human ALOX15 and investigated the impact of these mutations on structural, catalytic and allosteric enzyme properties.

View Article and Find Full Text PDF

The tree shrew (Tupaia belangeri) is a rat-sized mammal, which is more closely related to humans than mice and rats. However, the use of tree shrew to explore the patho-mechanisms of human inflammatory disorders has been limited since nothing is known about eicosanoid metabolism in this mammalian species. Eicosanoids are important lipid mediators exhibiting pro- and anti-inflammatory activities, which are biosynthesized via lipoxygenase and cyclooxygenase pathways.

View Article and Find Full Text PDF

For the specificity of ALOX15 orthologs of different mammals, the geometry of the amino acids Phe353, Ile418, Met419, and Ile593 ("triad determinants") is important, and mutagenesis of these residues altered the reaction specificity of these enzymes. Here we expressed wild-type human ALOX5 and its F359W/A424I/N425M/A603I mutant in Sf9 insect cells and characterized the catalytic differences of the two enzyme variants. We found that wild-type ALOX5 converted arachidonic acid mainly to 5()-hydroperoxyeicosatetraenoic acid (HpETE).

View Article and Find Full Text PDF
Article Synopsis
  • Arachidonate lipoxygenase (ALOX) isoforms are key in producing inflammatory leukotrienes and pro-resolving mediators, but the specific effects of certain mutations in ALOX5 are not well understood.
  • Researchers created knock-in mice with a specific triple mutation in the Alox5 gene to study the biological consequences of these alterations, demonstrating that the mutant enzyme favors the production of a beneficial compound called 13S-hydroxy linoleic acid (13S-HODE) instead of proinflammatory leukotrienes.
  • The mutant mice are healthy and fertile but exhibit increased body weight as they age, potentially linked to elevated levels of 13-HODE in their fat tissue, indicating how these genetic
View Article and Find Full Text PDF

Background: Atopic diseases constitute a major health challenge for industrialized countries, and elevated levels of interleukin 4 (IL-4) frequently characterize these disorders. Previous in vitroanalyses have indicated that IL-4 strongly upregulates the expression of IL-4-sensitive genes in human monocytes.

Objective: To explore whether similar expression alterations may contribute to the pathomechanisms of atopic diseases in vivo we carried out a small-scale case-control clinical study (n = 43), in which we quantified the plasma levels of IgE and IL-4 as well as the expression of selected IL-4-sensitive genes in blood leukocytes.

View Article and Find Full Text PDF

Arachidonic acid lipoxygenases (ALOXs) are lipid-metabolizing enzymes that have been implicated in cell differentiation, but also in the pathogenesis of inflammatory, hyperproliferative and neurological diseases. Most mammalian genomes involve six or seven functional ALOX genes and among the corresponding ALOX-isoforms the ALOX15 orthologs are somewhat unique since they exhibit variable reaction specificity using arachidonic acid as substrate. The Evolutionary Hypothesis of mammalian ALOX15 reaction specificity (Prog.

View Article and Find Full Text PDF

Lipoxygenases are lipid peroxidizing enzymes, which frequently occur in higher plants and mammals. These enzymes are also expressed in lower multicellular organisms but here they are not widely distributed. In bacteria, lipoxygenases rarely occur and evaluation of the currently available bacterial genomes suggested that <0.

View Article and Find Full Text PDF

Lipoxygenases are lipid peroxidizing enzymes, which frequently occur in higher plants and animals. In bacteria, these enzymes are rare and have been introduced via horizontal gene transfer. Since viruses function as horizontal gene transfer vectors and since lipoxygenases may be helpful for releasing assembled virus particles from host cells we explored whether these enzymes may actually occur in viruses.

View Article and Find Full Text PDF

A PHP Error was encountered

Severity: Warning

Message: fopen(/var/lib/php/sessions/ci_session5j5jcg5apgaanmkdnq2rngt1o923kme4): Failed to open stream: No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 177

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: session_start(): Failed to read session data: user (path: /var/lib/php/sessions)

Filename: Session/Session.php

Line Number: 137

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once