Catalase: an old enzyme with a new role?

1984 ◽  
Vol 62 (10) ◽  
pp. 1006-1014 ◽  
Author(s):  
Maire E. Percy
Keyword(s):  
Physiological Role ◽  
Electron Donors ◽  
Biologically Active ◽  
Intracellular Enzyme ◽  
Published Evidence ◽  
Erythrocyte Catalase ◽  
Low Concentrations ◽  
Adrenergic Antagonist ◽  
Health And Disease

Although animal catalase has been studied for decades, its physiological role has remained perplexing. It has two enzymatic functions, not only catalyzing the breakdown of H2O2 into O2 and H2O, but also in the presence of low concentrations of H2O2 catalyzing the oxidation of electron donors such as ethanol or phenols. In this article, I have summarized some well-known properties of the enzyme and have also described several recently discovered features. Of particular interest is the finding that, although catalase has been regarded as an intracellular enzyme, there is published evidence for its association with the plasma membrane of the erythrocyte. Moreover, recent work from my laboratory indicates that in vitro at alkaline pH in the presence of Mg2+, the biologically active diphenols (β-3,4-dihydroxyphenylalanine and the β-adrenergic agonists isoproterenol, norepinephrine, and epinephrine) appear to function as electron donor substrates for human erythrocyte catalase and inhibit the production of O2 from H2O2 at micromolar concentrations. The β-adrenergic antagonist propranolol inhibits O2 production much less effectively and appears to competitively inhibit the reaction of catalase with epinephrine. These observations suggest an analogy between catalase and the β-adrenergic hormone receptor and raise many questions of interest to basic science, health, and disease.

Potential Risks and Benefits of Phytoestrogen-Rich Diets

2003 ◽  
Vol 73 (2) ◽  
pp. 120-126 ◽  
Author(s):  
Cassidy
Keyword(s):  
Biological Effects ◽  
Physiological Role ◽  
Intestinal Bacteria ◽  
Optimal Dose ◽  
Biologically Active ◽  
Pharmacokinetic Data ◽  
Potential Health ◽  
Beneficial Effects ◽  
Age Related

Interest in the physiological role of bioactive compounds present in plants has increased dramatically over the last decade. Of particular interest in relation to human health are the class of compounds known as the phytoestrogens, which embody several groups of non-steroidal oestrogens including isoflavones & lignans that are widely distributed within the plant kingdom. Data from animal and in vitro studies provide plausible mechanisms to explain how phytoestrogens may influence hormone dependent states, but although the clinical application of diets rich in these oestrogen mimics is in its infancy, data from preliminary studies suggest potential beneficial effects of importance to health. Phytoestrogens are strikingly similar in chemical structure to the mammalian oestrogen, oestradiol, and bind to oestrogen receptors (ER) with a preference for the more recently described ERb. This suggests that these compounds may exert tissue specific effects. Numerous other biological effects independent of the ER (e.g. antioxidant capacity, antiproliferative and antiangiogenic effects) have been ascribed to these compounds. Whether phytoestrogens have any biological activity in humans, either hormonal or non hormonal is a contentious issue and there is currently a paucity of data on human exposure. Much of the available data on the absorption and metabolism of dietary phytoestrogens is of a qualitative nature; it is known that dietary phytoestrogens are metabolised by intestinal bacteria, absorbed, conjugated in the liver, circulated in plasma and excreted in urine. Recent studies have addressed quantitatively what happens to isoflavones following ingestion – with pure compound and stable isotope data to compliment recent pharmacokinetic data for soy foods. The limited studies conducted so far in humans clearly confirm that soya isoflavones can exert hormonal effects. These effects may be of benefit in the prevention of many of the common diseases observed in Western populations (such as breast cancer, prostate cancer, menopausal symptoms, osteoporosis) where the diet is typically devoid of these biologically active naturally occurring compounds. However since biological effects are dependent on many factors including dose, duration of use, protein binding affinity, individual metabolism and intrinsic oestrogenic state, further clinical studies are necessary to determine the potential health effects of these compounds in specific population groups. However we currently know little about age related differences in exposure to these compounds and there are few guidelines on optimal dose for specific health outcomes.

Abstract 489: Mechanisms of Carbon Monoxide Attenuation of Tubuloglomerular Feedback

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
YiLin Ren ◽  
Martin A D'Ambrosio ◽  
Hong Wang ◽  
Jeffrey L Garvin ◽  
Oscar A Carretero
Keyword(s):  
Carbon Monoxide ◽  
Physiological Role ◽  
Inhibitory Effect ◽  
Tubuloglomerular Feedback ◽  
Renal Microcirculation ◽  
Low Concentrations ◽  
Cgmp Analog ◽  
Cell Depolarization ◽  
Toxic Concentrations

Tubuloglomerular feedback (TGF) is an autoregulatory mechanism of the renal microcirculation in which the macula densa (MD) senses NaCl concentration in the lumen of the nephron and sends a signal that controls glomerular filtration rate by constricting the afferent arteriole (Af-Art). We have shown that MD depolarization is sufficient for inducing TGF. Carbon monoxide (CO), either endogenous or exogenous, is known to inhibit TGF, at least in part via cGMP. However, whether cGMP-independent mechanisms are involved, and where in the TGF cascade CO exerts its inhibitory effect, remain unknown. Thus we hypothesize that CO, acting via both cGMP-dependent and -independent mechanisms, attenuates TGF by acting downstream from MD cell depolarization. In vitro , microdissected rabbit Af-Arts and their attached MD were simultaneously perfused and TGF was measured as the decrease in Af-Art diameter. Depolarization of the MD was induced by switching luminal KCl from 4 to 50 mM in the presence of the potassium ionophore valinomycin, while adding the CO-releasing molecule CORM-3 to the MD perfusate at non-toxic concentrations. CORM-3 blunted depolarization-induced TGF at a concentration of 50 μM, from 3.6±0.4 to 2.5±0.4 μm (P<0.01), and completely abolished it at a concentration of 100 μM, to 0.1±0.1 μm (P<0.001, n=6). Similar results were found with 100 μM CORM-3 when depolarization was induced by nystatin (3.0±0.2 vs. 0.4±0.2 μm, P <0.001, n=6). This indicates that CO inhibits TGF acting downstream from depolarization. When cGMP generation was blocked with the guanylate cyclase inhibitor LY-83583 (1 μM) added to the MD, CORM-3 no longer had an effect on depolarization-induced TGF at 50 μM (2.9±0.4 vs. 3.0±0.4 μm), but retained partial inhibitory effect on TGF at 100 μM (1.3±0.2 μm, P =0.02, n=9). This suggests that CO acts via cGMP at low concentrations, but additional mechanisms of action may be involved at higher concentrations. Finally, we confirmed that cGMP inhibits TGF downstream from MD depolarization by adding the degradation-resistant cGMP analog dibutyryl-cGMP (500 μM), which attenuated depolarization-induced TGF (from 3.9±0.5 to 0.6±0.2 μm, P <0.01, n=6). Our results could help explain the physiological role of CO in controlling the renal microcirculation.

scholarly journals Fermented Foods: Definitions and Characteristics, Impact on the Gut Microbiota and Effects on Gastrointestinal Health and Disease

Nutrients ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1806 ◽  
Author(s):  
Eirini Dimidi ◽  
Selina Rose Cox ◽  
Megan Rossi ◽  
Kevin Whelan
Keyword(s):  
Controlled Trial ◽  
Health Benefits ◽  
Biologically Active ◽  
Fermented Foods ◽  
Lactose Malabsorption ◽  
Gastrointestinal Health ◽  
Sourdough Bread ◽  
Health And Disease ◽  
The Impact

Fermented foods are defined as foods or beverages produced through controlled microbial growth, and the conversion of food components through enzymatic action. In recent years, fermented foods have undergone a surge in popularity, mainly due to their proposed health benefits. The aim of this review is to define and characterise common fermented foods (kefir, kombucha, sauerkraut, tempeh, natto, miso, kimchi, sourdough bread), their mechanisms of action (including impact on the microbiota), and the evidence for effects on gastrointestinal health and disease in humans. Putative mechanisms for the impact of fermented foods on health include the potential probiotic effect of their constituent microorganisms, the fermentation-derived production of bioactive peptides, biogenic amines, and conversion of phenolic compounds to biologically active compounds, as well as the reduction of anti-nutrients. Fermented foods that have been tested in at least one randomised controlled trial (RCT) for their gastrointestinal effects were kefir, sauerkraut, natto, and sourdough bread. Despite extensive in vitro studies, there are no RCTs investigating the impact of kombucha, miso, kimchi or tempeh in gastrointestinal health. The most widely investigated fermented food is kefir, with evidence from at least one RCT suggesting beneficial effects in both lactose malabsorption and Helicobacter pylori eradication. In summary, there is very limited clinical evidence for the effectiveness of most fermented foods in gastrointestinal health and disease. Given the convincing in vitro findings, clinical high-quality trials investigating the health benefits of fermented foods are warranted.

Calcium-translocating and cardiotonic properties of oxidation products of linoleic acid

1985 ◽  
Vol 63 (11) ◽  
pp. 1392-1397 ◽  
Author(s):  
Ryungsoon Song Kim ◽  
Ivan Bihler ◽  
Frank S. LaBella
Keyword(s):  
Linoleic Acid ◽  
Calcium Ionophore ◽  
Physiological Role ◽  
Calcium Ionophore A23187 ◽  
Oxidation Products ◽  
Ionophore A23187 ◽  
Guinea Pig Heart ◽  
Adrenergic Antagonist

Calcium-translocating activity of linoleic acid and its lipoxygenase (linoleate: oxygen oxidoreductase; EC 1.13.11.12) metabolites or autoxidation products was determined in vitro by estimation of 45Ca transport from a bulk aqueous to a bulk organic phase. Fresh commercial linoleic acid, tested immediately after removal from a sealed vial, stimulated calcium translocation only at concentrations greater than 1 mM. In contrast, 45Ca translocation by linoleic acid exposed to air was detectable at 10 μM. Oxidation products of linoleic acid obtained either by incubation with lipoxygenase or by autoxidation were much less potent than the calcium ionophore A23187. The products obtained by enzymic oxidation of linoleic acid enhanced contractility in the Langendorff-perfused guinea pig heart up to 45% over control (at 3 × 10−8 M). The inotropic response was transient with rapid onset and not affected by the beta-adrenergic antagonist, propranolol. The autoxidation products of linoleic acid increased cardiac contractility up to 43% at 10−6 M. In contrast, fresh linoleic acid caused only a negative inotropic effect at 10−8 to 3 × 10−7 M, progressing to contracture at 10−6 M. These findings suggest that conflicting reports on the cardiostimulant effect of linoleic acid may be due to varying levels of the autoxidation products. Linoleic acid metabolites in vivo may have a physiological role in myocardial function related to their Ca2+-ionophoric activity.

Extracellular Nucleoside Diphosphate Kinase NDPK/Nm23 Protein Isoforms A and B Support Erythropoiesis and Have a Burst-Promoting Activity.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1625-1625
Author(s):  
Zwi N. Berneman ◽  
Roel Willems ◽  
Griet Nijs ◽  
Marc Lenjou ◽  
Dirk R. Van Bockstaele
Keyword(s):  
Physiological Role ◽  
Nucleoside Diphosphate Kinase ◽  
Fold Increase ◽  
Protein Isoforms ◽  
Bone Marrow Mononuclear Cell ◽  
Gm Csf ◽  
Low Concentrations ◽  
High Concentrations ◽  
Macrophage Colony

Abstract We previously demonstrated the in vitro hematopoietic effects of different nucleoside diphosphate kinase NDPK/Nm23 proteins, i.e. increase of burst-forming units erythroid (BFU-E) and decrease of colony-forming units macrophage (CFU-M) (Willems R et al. Experimental Hematology2002;30: 640–648). The effect was especially pronounced in the marrows that had a particular low BFU-E count. Since these experiments were performed under optimal erythroid growth factor stimulation including adequately high concentrations of erythropoietin (Epo) and stem cell factor (SCF 100 ng/mL), subtle effects of NDPK/Nm23 proteins on erythropoiesis could have been missed. In the present series of experiments on 7 normal bone marrow mononuclear cell suspensions, we deliberately created suboptimal in vitro conditions for early (BFU-E) erythropoiesis: i.e. serum free conditions with a limited number of cytokines (only Epo and SCF) and a low concentration of burst-promoting activity (SCF at 5 ng/ml). The results show that addition of NDPK A/Nm23-H1 and NDPK B/Nm23- H2 (but not of NDPK C) at high (40 μg/mL), but not low, extracellular concentration is sustaining and improving in vitro erythropoiesis in a statistically significant manner (P<0.05). Red cell colonies increased by a factor of 1.9 and 1.4 following addition of NDPK A/Nm23-H1 and NDPK B/Nm23- H2 respectively. Especially with NDPK A/Nm23-H1, this approaches levels attained under optimal conditions for erythropoiesis, i.e. at SCF concentration of 100 ng/mL, where a 2.1-fold increase was seen, as compared to cultures with low concentrations of SCF (5 ng/mL) without addition of extracellular NDPK/Nm23. In cultures without Epo no erythroid colonies were seen, even following addition of NDPK A/Nm23-H1 or NDPK B/Nm23-H2. This study strongly suggests that NDPK/Nm23 has a burst-promoting activity. The fairly high concentrations of NDPK/Nm23 constitutively present in plasma supports the physiological role of this protein in stimulating early erythropoiesis. Of the (known) cytokines or proteins with burst-promoting activity (eg. SCF, interleukin 3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), NDPK/Nm23 (this study)), only SCF and NDPK/Nm23 are produced in a constitutive fashion, strongly supporting their role in the steady-state support of early erythropoiesis.

Utilizing in vitro DNA assembly to engineer a synthetic T7 Nanoluc reporter phage for Escherichia coli detection

2019 ◽  
Vol 11 (3) ◽  
pp. 63-68 ◽  
Author(s):  
Elsi M Pulkkinen ◽  
Troy C Hinkley ◽  
Sam R Nugen
Keyword(s):  
Escherichia Coli ◽  
Liquid Culture ◽  
Detection Methods ◽  
Luciferase Expression ◽  
Dna Assembly ◽  
Bacterial Populations ◽  
Low Concentrations ◽  
Health And Disease ◽  
T7 Phage

Abstract Bacteria have major role in regulating human health and disease, therefore, there is a continuing need to develop new detection methods and therapeutics to combat them. Bacteriophages can be used to infect specific bacteria, which make them good candidates for detecting and editing bacterial populations. However, creating phage-based detection assays is somewhat limited by the difficulties in the engineering of phages. We present here a synthetic biology strategy to engineer phages using a simple in vitro method. We used this method to insert a NanoLuc luciferase expression cassette into the T7 phage, in order to construct the NRGp6 reporter phage. The synthetic NRGp6 phage was used to efficiently detect low concentrations of Escherichia coli from liquid culture. We envision that our approach will benefit synthetic biologists for constructing different kinds of engineered phages, and enable new approaches for phage-based therapeutics and diagnostics.

scholarly journals Thymulin gene therapy prevents the reduction in circulating gonadotropins induced by thymulin deficiency in mice

2007 ◽  
Vol 293 (1) ◽  
pp. E182-E187 ◽  
Author(s):  
Rodolfo G. Goya ◽  
Paula C. Reggiani ◽  
Silvan M. Vesenbeckh ◽  
Jean M. Pléau ◽  
Yolanda E. Sosa ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Mammalian Species ◽  
Physiological Role ◽  
Serum Levels ◽  
Biologically Active ◽  
Short Term ◽  
Active Analog ◽  
Synthetic Dna ◽  
Thymic Peptide

Integrity of the thymus during perinatal life is necessary for a proper maturation of the pituitary-gonadal axis in mice and other mammalian species. Thus congenitally athymic (nude) female mice show significantly reduced levels of circulating gonadotropins, a fact that seems to be causally related to a number of reproductive derangements described in these mutants. Interestingly, a number of in vitro studies suggest that the thymic peptide thymulin may be involved in thymus-pituitary communication. To determine the consequences of low serum thymulin in otherwise normal animals, we induced short (8 days)- and long (33 days)-term thymulin deficiency in C57BL/6 mice by neonatally injecting (intraperitoneally) an anti-thymulin serum and assessed their circulating gonadotropin levels at puberty and thereafter. Control mice received an irrelevant antiserum. Gonadotropins were measured by radioimmunoassay and thymulin by bioassay. Both long- and short-term serum thymulin immunoneutralization resulted in a significant reduction in the serum levels of gonadotropins at 33 and 45 days of age. Subsequently, we injected (intramuscularly) an adenoviral vector harboring a synthetic DNA sequence (5′-ATGCAAGCCAAATCTCAAGGTGGATCCAACTAGTAG-3′) encoding a biologically active analog of thymulin, methionine-FTS, in newborn nude mice (which are thymulin deficient) and measured circulating gonadotropin levels when the animals reached 52 days of age. It was observed that neonatal thymulin gene therapy in the athymic mice restored their serum thymulin levels and prevented the reduction in circulating gonadotropin levels that typically emerges in these mutants after puberty. Our results indicate that thymulin plays a relevant physiological role in the thymus-pituitary-gonadal axis.

A nanobody-based method for tracking factor XII activation in plasma

2013 ◽  
Vol 110 (09) ◽  
pp. 458-468 ◽  
Author(s):  
Steven de Maat ◽  
Sanne van Dooremalen ◽  
Philip G. Groot ◽  
Coen Maas
Keyword(s):  
Catalytic Domain ◽  
Physiological Role ◽  
Coagulation Factor ◽  
Factor Xii ◽  
Protein Factor ◽  
Inflammatory Conditions ◽  
Human Pathology ◽  
Activation Products ◽  
Health And Disease

SummaryThe physiological role of the plasma protein factor XII (FXII), as well as its involvement in human pathology, is poorly understood. While FXII is implicated in thrombotic pathology as a coagulation factor, it can contribute to inflammatory conditions without triggering coagulation. We recently generated nanobodies against the catalytic domain of activated FXII (FXIIa). Here, we describe two of these nanobodies, A10 and B7, both of which do not recognise FXII. Nanobody A10 recognises the catalytic domain of purified β-FXIIa (80 kDa), but not that of purified α-FXIIa (28 kDa), whereas nanobody B7 recognises both. This suggests minute differences in the catalytic domain between these isoforms of FXIIa. The detection of FXIIa by these nanobodies in plasma can become compromised through inactivation by serine protease inhibitors. This effect can be efficiently countered through the addition of the small-molecular protease inhibitor PPACK. Finally, we show that our nanobody-based assays in vitro distinguish various activation products of FXII that differ with the type of activator present: whereas procoagulant activators solely trigger the formation of a species that is captured by B7, proinflammatory activators first generate a species that is recognised by B7, which is later converted into a species that is recognised by A10. These findings suggest that a progressive proteolysis of FXIIa results in the generation a non-procoagulant form of FXIIa, whereas retention of intermediate forms triggers coagulation. Moreover, our findings indicate the development of nanobodies against activated enzymes offers improved opportunities to investigate their contribution to health and disease.

scholarly journals Control of Astrocyte Quiescence and Activation in a Synthetic Brain Hydrogel

2019 ◽  
Author(s):  
Sualyneth Galarza ◽  
Alfred J. Crosby ◽  
ChangHui Pak ◽  
Shelly R. Peyton
Keyword(s):  
Physiological Role ◽  
Protein Composition ◽  
Culture Conditions ◽  
Quiescent State ◽  
Dependent Manner ◽  
Synthetic Hydrogel ◽  
Health And Disease ◽  
And Control ◽  
First Time

Bioengineers designed numerous instructive brain extracellular matrix (ECM) environments that have tailored and tunable protein composition and biomechanics in vitro to study astrocyte reactivity during trauma and inflammation. However, a major limitation of both protein-based and model microenvironments is that astrocytes within fail to retain their characteristic stellate morphology and quiescent state without becoming activated under “normal” culture conditions. Here we introduce a synthetic hydrogel, that for the first time demonstrates maintenance of astrocyte quiescence, and control over activation on demand. With this synthetic brain hydrogel, we show the brain-specific integrin-binding and matrix metalloprotease (MMP)-degradable domains of proteins control astrocyte star-shaped morphologies, and we can achieve an ECM condition that maintains astrocyte quiescence with minimal activation. In addition, we can induce activation in a dose-dependent manner via both defined cytokine cocktails and low molecular weight hyaluronic acid. We envision this synthetic brain hydrogel as a new tool to study the physiological role of astrocytes in health and disease.

Kinetics of Various 99mTc-Sn-Pyrophosphate Compounds in the Rat

1977 ◽  
Vol 16 (04) ◽  
pp. 157-162 ◽  
Author(s):  
C. Schümichen ◽  
B. Mackenbrock ◽  
G. Hoffmann
Keyword(s):  
Normal Saline ◽  
Half Life ◽  
Compound A ◽  
Short Half Life ◽  
Low Concentrations ◽  
The Stability ◽  
Kinetics Of ◽  
In Vitro Stability

SummaryThe bone-seeking 99mTc-Sn-pyrophosphate compound (compound A) was diluted both in vitro and in vivo and proved to be unstable both in vitro and in vivo. However, stability was much better in vivo than in vitro and thus the in vitro stability of compound A after dilution in various mediums could be followed up by a consecutive evaluation of the in vivo distribution in the rat. After dilution in neutral normal saline compound A is metastable and after a short half-life it is transformed into the other 99mTc-Sn-pyrophosphate compound A is metastable and after a short half-life in bone but in the kidneys. After dilution in normal saline of low pH and in buffering solutions the stability of compound A is increased. In human plasma compound A is relatively stable but not in plasma water. When compound B is formed in a buffering solution, uptake in the kidneys and excretion in urine is lowered and blood concentration increased.It is assumed that the association of protons to compound A will increase its stability at low concentrations while that to compound B will lead to a strong protein bond in plasma. It is concluded that compound A will not be stable in vivo because of a lack of stability in the extravascular space, and that the protein bond in plasma will be a measure of its in vivo stability.

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