60 results match your criteria demonstrate arg2

Renal tubular arginase-2 participates in the formation of the corticomedullary urea gradient and attenuates kidney damage in ischemia-reperfusion injury in mice.

Acta Physiol (Oxf) 2020 07 10;229(3):e13457. Epub 2020 Mar 10.

Department of Pharmacology and Toxicology, University of Lausanne, Lausanne, Switzerland.

Aim: Arginase 2 (ARG2) is a mitochondrial enzyme that catalyses hydrolysis of l-arginine into urea and l-ornithine. In the kidney, ARG2 is localized to the S3 segment of the proximal tubule. It has been shown that expression and activity of this enzyme are upregulated in a variety of renal pathologies, including ischemia-reperfusion (IR) injury. Read More

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Macrophage-Derived IL1β and TNFα Regulate Arginine Metabolism in Neuroblastoma.

Cancer Res 2019 02 13;79(3):611-624. Epub 2018 Dec 13.

Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.

Neuroblastoma is the most common childhood solid tumor, yet the prognosis for high-risk disease remains poor. We demonstrate here that arginase 2 (ARG2) drives neuroblastoma cell proliferation via regulation of arginine metabolism. Targeting arginine metabolism, either by blocking cationic amino acid transporter 1 (CAT-1)-dependent arginine uptake or therapeutic depletion of arginine by pegylated recombinant arginase BCT-100, significantly delayed tumor development and prolonged murine survival. Read More

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February 2019

Arginase II Contributes to the Ca/CaMKII/eNOS Axis by Regulating Ca Concentration Between the Cytosol and Mitochondria in a p32-Dependent Manner.

J Am Heart Assoc 2018 09;7(18):e009579

1 Department of Biology School of medicine Kangwon National University Chuncheon Korea.

Background Arginase II activity contributes to reciprocal regulation of endothelial nitric oxide synthase ( eNOS ). We tested the hypotheses that arginase II activity participates in the regulation of Ca/Ca/calmodulin-dependent kinase II / eNOS activation, and this process is dependent on mitochondrial p32. Methods and Results Downregulation of arginase II increased the concentration of cytosolic Ca ([Ca]c) and decreased mitochondrial Ca ([Ca]m) in microscopic and fluorescence-activated cell sorting analyses, resulting in augmented eNOS Ser1177 phosphorylation and decreased eNOS Thr495 phosphorylation through Ca/Ca/calmodulin-dependent kinase II . Read More

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September 2018

Hypoxic-induction of arginase II requires EGF-mediated EGFR activation in human pulmonary microvascular endothelial cells.

Physiol Rep 2018 05;6(10):e13693

Pulmonary Hypertension Group, Center for Perinatal Research, Research Institute at Nationwide Children's Hospital, Columbus, Ohio.

We have previously shown that hypoxia-induced proliferation of human pulmonary microvascular endothelial cells (hPMVEC) depends on arginase II, and that epidermal growth factor receptor (EGFR) is necessary for hypoxic-induction of arginase II. However, it remains unclear how hypoxia activates EGFR-mediated signaling in hPMVEC. We hypothesized that hypoxia results in epidermal growth factor (EGF) production and that EGF binds to EGFR to activate the signaling cascade leading to arginase II induction and proliferation in hPMVEC. Read More

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CD71 Erythroid Suppressor Cells Promote Fetomaternal Tolerance through Arginase-2 and PDL-1.

J Immunol 2018 06 7;200(12):4044-4058. Epub 2018 May 7.

Department of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, T6G 2E1 Alberta, Canada;

Survival of the allogeneic pregnancy depends on the maintenance of immune tolerance to paternal alloantigens at the fetomaternal interface. Multiple localized mechanisms contribute to the fetal evasion from the mother's immune rejection as the fetus is exposed to a wide range of stimulatory substances such as maternal alloantigens, microbes and amniotic fluids. In this article, we demonstrate that CD71 erythroid cells are expanded at the fetomaternal interface and in the periphery during pregnancy in both humans and mice. Read More

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Arginase-II negatively regulates renal aquaporin-2 and water reabsorption.

FASEB J 2018 10 2;32(10):5520-5531. Epub 2018 May 2.

Division of Physiology, Department of Medicine, Cardiovascular and Aging Research, University of Fribourg, Fribourg, Switzerland.

Type-II l-arginine:ureahydrolase, arginase-II (Arg-II), is abundantly expressed in the kidney. The physiologic role played by Arg-II in the kidney remains unknown. Herein, we report that in mice that are deficient in Arg-II (Arg-II), total and membrane-associated aquaporin-2 (AQP2) protein levels were significantly higher compared with wild-type (WT) controls. Read More

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October 2018

Arginase-II activates mTORC1 through myosin-1b in vascular cell senescence and apoptosis.

Cell Death Dis 2018 02 22;9(3):313. Epub 2018 Feb 22.

Cardiovascular and Aging Research, Department of Medicine, Division of Physiology, University of Fribourg, Chemin du Musée 5, 1700, Fribourg, Switzerland.

Type-II L-arginine:ureahydrolase, arginase-II (Arg-II), is shown to activate mechanistic target of rapamycin complex 1 (mTORC1) pathway and contributes to cell senescence and apoptosis. In an attempt to elucidate the underlying mechanism, we identified myosin-1b (Myo1b) as a mediator. Overexpression of Arg-II induces re-distribution of lysosome and mTOR but not of tuberous sclerosis complex (TSC) from perinuclear area to cell periphery, dissociation of TSC from lysosome and activation of mTORC1-ribosomal protein S6 kinase 1 (S6K1) pathway. Read More

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February 2018

Altered Expression of Urea Cycle Enzymes in Amyloid-β Protein Precursor Overexpressing PC12 Cells and in Sporadic Alzheimer's Disease Brain.

J Alzheimers Dis 2018 ;62(1):279-291

Department of Cellular Signalling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.

Urea cycle enzymes may play important yet poorly characterized roles in Alzheimer's disease (AD). Our previous results showed that amyloid-β (Aβ) affects urea cycle enzymes in rat pheochromocytoma (PC12) cells. The aim of the present study was to investigate the changes in arginases, other urea cycle enzymes, and nitric oxide synthases (NOSs) in PC12 cells transfected with AβPP bearing the double 'Swedish' mutation (APPsw, K670M/N671L) and in postmortem sporadic AD brain hippocampus; the mutation intensifies Aβ production and strongly associates with AD neuropathology. Read More

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Binding and entry of peste des petits ruminants virus into caprine endometrial epithelial cells profoundly affect early cellular gene expression.

Vet Res 2018 01 24;49(1). Epub 2018 Jan 24.

College of Veterinary Medicine, Northwest A&F University, Yangling, 712100, Shaanxi, China.

Peste des petits ruminants virus (PPRV), the etiological agent of peste des petits ruminants (PPR), causes an acute or subacute disease in small ruminants. Although abortion is observed in an unusually large proportion of pregnant goats during outbreaks of PPR, the pathogenic mechanism underlying remains unclear. Here, the gene expression profile of caprine endometrial epithelial cells (EECs) infected with PPRV Nigeria 75/1 was determined by DNA microarray to investigate the cellular response immediately after viral entry. Read More

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January 2018

Inhibition of arginase by CB-1158 blocks myeloid cell-mediated immune suppression in the tumor microenvironment.

J Immunother Cancer 2017 12 19;5(1):101. Epub 2017 Dec 19.

Calithera Biosciences, 343 Oyster Point Boulevard, Suite 200, South San Francisco, CA, 94080, USA.

Background: Myeloid cells are an abundant leukocyte in many types of tumors and contribute to immune evasion. Expression of the enzyme arginase 1 (Arg1) is a defining feature of immunosuppressive myeloid cells and leads to depletion of L-arginine, a nutrient required for T cell and natural killer (NK) cell proliferation. Here we use CB-1158, a potent and orally-bioavailable small-molecule inhibitor of arginase, to investigate the role of Arg1 in regulating anti-tumor immunity. Read More

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December 2017

Dystonia-4 (DYT4)-associated TUBB4A mutants exhibit disorganized microtubule networks and inhibit neuronal process growth.

Biochem Biophys Res Commun 2018 01 7;495(1):346-352. Epub 2017 Nov 7.

Laboratory of Molecular Neuroscience and Neurology, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan; Department of Pharmacology, National Research Institute for Child Health and Development, Setagaya, Tokyo 157-8535, Japan. Electronic address:

Dystonia-1 (DYT1) is an autosomal dominant early-onset torsion form of dystonia, a neurological disease affecting movement. DYT1 is the prototypic hereditary dystonia and is caused by the mutation of the tor1a gene. The gene product has chaperone functions important for the control of protein folding and stability. Read More

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January 2018

Hypoxia-induced proliferation of HeLa cells depends on epidermal growth factor receptor-mediated arginase II induction.

Physiol Rep 2017 Mar;5(6)

Pulmonary Hypertension Group, Center for Perinatal Research The Research Institute at Nationwide Children's Hospital, Columbus, Ohio

Solid tumors can often be hypoxic in regions, and cancer cells can respond to hypoxia with an increase in proliferation and a decrease in apoptosis, leading to a net increase in viable cell numbers. We have recently found that in an osteosarcoma cell line, hypoxia-induced proliferation depends on arginase II induction. Epidermal growth factor receptor (EGFR) has been shown to mediate the hypoxia-induced cellular proliferation in some cancer cell lines. Read More

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Hypoxia induces arginase II expression and increases viable human pulmonary artery smooth muscle cell numbers via AMPKα signaling.

Am J Physiol Lung Cell Mol Physiol 2017 04 17;312(4):L568-L578. Epub 2017 Feb 17.

Pulmonary Hypertension Group, Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio; and

Pulmonary artery smooth muscle cell (PASMC) proliferation is one of the hallmark features of hypoxia-induced pulmonary hypertension. With only supportive treatment options available for this life-threatening disease, treating and preventing the proliferation of PASMCs is a viable therapeutic option. A key promoter of hypoxia-induced increases in the number of viable human PASMCs is arginase II, with attenuation of viable cell numbers following pharmacologic inhibition or siRNA knockdown of the enzyme. Read More

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Amino Acid Catabolism in Multiple Sclerosis Affects Immune Homeostasis.

J Immunol 2017 03 27;198(5):1900-1909. Epub 2017 Jan 27.

Department of Neurology, Raúl Carrea Institute for Neurological Research, FLENI, 1428 Buenos Aires, Argentina

Amino acid catabolism has been implicated in immunoregulatory mechanisms present in several diseases, including autoimmune disorders. Our aims were to assess expression and activity of enzymes involved in Trp and Arg catabolism, as well as to investigate amino acid catabolism effects on the immune system of multiple sclerosis (MS) patients. To this end, 40 MS patients, 30 healthy control subjects, and 30 patients with other inflammatory neurological diseases were studied. Read More

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Increased mitochondrial arginine metabolism supports bioenergetics in asthma.

J Clin Invest 2016 07 23;126(7):2465-81. Epub 2016 May 23.

High levels of arginine metabolizing enzymes, including inducible nitric oxide synthase (iNOS) and arginase (ARG), are typical in asthmatic airway epithelium; however, little is known about the metabolic effects of enhanced arginine flux in asthma. Here, we demonstrated that increased metabolism sustains arginine availability in asthmatic airway epithelium with consequences for bioenergetics and inflammation. Expression of iNOS, ARG2, arginine synthetic enzymes, and mitochondrial respiratory complexes III and IV was elevated in asthmatic lung samples compared with healthy controls. Read More

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Arginase 2 deletion leads to enhanced M1 macrophage activation and upregulated polyamine metabolism in response to Helicobacter pylori infection.

Amino Acids 2016 10 13;48(10):2375-88. Epub 2016 Apr 13.

Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Vanderbilt University School of Medicine, 2215 Garland Avenue, 1030C Medical Research Building IV, Nashville, TN, 37232, USA.

We reported that arginase 2 (ARG2) deletion results in increased gastritis and decreased bacterial burden during Helicobacter pylori infection in mice. Our studies implicated a potential role for inducible nitric oxide (NO) synthase (NOS2), as Arg2 (-/-) mice exhibited increased NOS2 levels in gastric macrophages, and NO can kill H. pylori. Read More

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October 2016

Analysis of human breast milk cells: gene expression profiles during pregnancy, lactation, involution, and mastitic infection.

Funct Integr Genomics 2016 May 24;16(3):297-321. Epub 2016 Feb 24.

Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, 3800, Australia.

The molecular processes underlying human milk production and the effects of mastitic infection are largely unknown because of limitations in obtaining tissue samples. Determination of gene expression in normal lactating women would be a significant step toward understanding why some women display poor lactation outcomes. Here, we demonstrate the utility of RNA obtained directly from human milk cells to detect mammary epithelial cell (MEC)-specific gene expression. Read More

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Targeting arginase-II protects mice from high-fat-diet-induced hepatic steatosis through suppression of macrophage inflammation.

Sci Rep 2016 Feb 5;6:20405. Epub 2016 Feb 5.

Vascular Biology, Department of Medicine, Division of Physiology, University of Fribourg, Chemin du Musée 5, CH-1700 Fribourg, Switzerland.

Nonalcoholic fatty liver disease (NAFLD) associates with obesity and type 2 diabetes. Hypoactive AMP-activated protein kinase (AMPK), hyperactive mammalian target of rapamycin (mTOR) signaling, and macrophage-mediated inflammation are mechanistically linked to NAFLD. Studies investigating roles of arginase particularly the extrahepatic isoform arginase-II (Arg-II) in obesity-associated NAFLD showed contradictory results. Read More

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February 2016

Neuroblastoma Arginase Activity Creates an Immunosuppressive Microenvironment That Impairs Autologous and Engineered Immunity.

Cancer Res 2015 Aug 8;75(15):3043-53. Epub 2015 Jun 8.

School of Cancer Sciences, University of Birmingham, Birmingham, United Kingdom.

Neuroblastoma is the most common extracranial solid tumor of childhood, and survival remains poor for patients with advanced disease. Novel immune therapies are currently in development, but clinical outcomes have not matched preclinical results. Here, we describe key mechanisms in which neuroblastoma inhibits the immune response. Read More

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Role of p38 mitogen-activated protein kinase in vascular endothelial aging: interaction with Arginase-II and S6K1 signaling pathway.

Aging (Albany NY) 2015 Jan;7(1):70-81

Laboratory of Vascular Biology, Department of Medicine, Division of Physiology, University of Fribourg, CH-1700 Fribourg, Switzerland.

p38 mitogen-activated protein kinase (p38) regulates cellular senescence and senescence-associated secretory phenotype (SASP), i.e., secretion of cytokines and/or chemokines. Read More

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January 2015

ARG2 impairs endothelial autophagy through regulation of MTOR and PRKAA/AMPK signaling in advanced atherosclerosis.

Autophagy 2014 ;10(12):2223-38

a Vascular Biology; Department of Medicine; Division of Physiology; Faculty of Science ; University of Fribourg ; Fribourg , Switzerland.

Impaired autophagy function and enhanced ARG2 (arginase 2)-MTOR (mechanistic target of rapamycin) crosstalk are implicated in vascular aging and atherosclerosis. We are interested in the role of ARG2 and the potential underlying mechanism(s) in modulation of endothelial autophagy. Using human nonsenescent "young" and replicative senescent endothelial cells as well as Apolipoprotein E-deficient (apoe(-/-)Arg2(+/+)) and Arg2-deficient apoe(-/-) (apoe(-/-)arg2(-/-)) mice fed a high-fat diet for 10 wk as the atherosclerotic animal model, we show here that overexpression of ARG2 in the young cells suppresses endothelial autophagy with concomitant enhanced expression of RICTOR, the essential component of the MTORC2 complex, leading to activation of the AKT-MTORC1-RPS6KB1/S6K1 (ribosomal protein S6 kinase, 70kDa, polypeptide 1) cascade and inhibition of PRKAA/AMPK (protein kinase, AMP-activated, α catalytic subunit). Read More

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December 2015

Extracellular signal-regulated kinase mediates expression of arginase II but not inducible nitric-oxide synthase in lipopolysaccharide-stimulated macrophages.

J Biol Chem 2015 Jan 1;290(4):2099-111. Epub 2014 Dec 1.

From the Pulmonary Hypertension Group, Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio 43215

The mitogen-activated protein kinases (MAPK) have been shown to participate in iNOS induction following lipopolysaccharide (LPS) stimulation, while the role of MAPKs in the regulation of arginase remains unclear. We hypothesized that different MAPK family members are involved in iNOS and arginase expression following LPS stimulation. LPS-stimulated RAW 264. Read More

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January 2015

Arginase 2 deficiency prevents oxidative stress and limits hyperoxia-induced retinal vascular degeneration.

PLoS One 2014 6;9(11):e110604. Epub 2014 Nov 6.

Vascular Biology Center, Georgia Regents University, Augusta, Georgia, United States of America; Culver Vision Discovery Institute, Georgia Regents University, Augusta, Georgia, United States of America; Charlie Norwood VA Medical Center, Augusta, Georgia, United States of America.

Background: Hyperoxia exposure of premature infants causes obliteration of the immature retinal microvessels, leading to a condition of proliferative vitreoretinal neovascularization termed retinopathy of prematurity (ROP). Previous work has demonstrated that the hyperoxia-induced vascular injury is mediated by dysfunction of endothelial nitric oxide synthase resulting in peroxynitrite formation. This study was undertaken to determine the involvement of the ureahydrolase enzyme arginase in this pathology. Read More

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p38 mitogen-activated protein kinase is involved in arginase-II-mediated eNOS-uncoupling in obesity.

Cardiovasc Diabetol 2014 Jul 18;13:113. Epub 2014 Jul 18.

Laboratory of Vascular Biology, Department of Medicine, Division of Physiology, University of Fribourg, Chemin du Musée 5, CH-1700, Fribourg, Switzerland.

Background: Endothelial nitric oxide synthase (eNOS)-uncoupling links obesity-associated insulin resistance and type-II diabetes to the increased incidence of cardiovascular disease. Studies have indicated that increased arginase is involved in eNOS-uncoupling through competing with the substrate L-arginine. Given that arginase-II (Arg-II) exerts some of its biological functions through crosstalk with signal transduction pathways, and that p38 mitogen-activated protein kinase (p38mapk) is involved in eNOS-uncoupling, we investigated here whether p38mapk is involved in Arg-II-mediated eNOS-uncoupling in a high fat diet (HFD)-induced obesity mouse model. Read More

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OxLDL triggers retrograde translocation of arginase2 in aortic endothelial cells via ROCK and mitochondrial processing peptidase.

Circ Res 2014 Aug 5;115(4):450-9. Epub 2014 Jun 5.

From the Department of Anesthesiology and Critical Care Medicine (D.P., A.B., Y.J.O., F.C., Y.B., J.H.K., J.S., D.E.B., L.H.R.), Biomedical Engineering (J.S., D.E.B., L.H.R.), and Cell Biology, Pediatrics, Center for Cell Dynamics (L.H.R.), Mass Spectrometry and Proteomics Facility (T.N.B., R.N.C.), and Departments of Medicine and Biological Chemistry (J.V.E.), Johns Hopkins University School of Medicine, Baltimore, MD; and Lipoprotein Metabolism Section, Cardiovascular-Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (A.T.R.).

Rationale: Increased arginase activity contributes to endothelial dysfunction by competition for l-arginine substrate and reciprocal regulation of nitric oxide synthase (NOS). The rapid increase in arginase activity in human aortic endothelial cells exposed to oxidized low-density lipoprotein (OxLDL) is consistent with post-translational modification or subcellular trafficking.

Objective: To test the hypotheses that OxLDL triggers reverse translocation of mitochondrial arginase 2 (Arg2) to cytosol and Arg2 activation, and that this process is dependent on mitochondrial processing peptidase, lectin-like OxLDL receptor-1 receptor, and rho kinase. Read More

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Role for high-glucose-induced protein O-GlcNAcylation in stimulating cardiac fibroblast collagen synthesis.

Am J Physiol Cell Physiol 2014 May 19;306(9):C794-804. Epub 2014 Feb 19.

Seccion de Posgrado, Escuela Superior de Medicina, Instituto Politecnico Nacional, Ciudad de Mexico, Mexico.

Excess enzyme-mediated protein O-GlcNAcylation is known to occur with diabetes mellitus. A characteristic of diabetic cardiomyopathy is the development of myocardial fibrosis. The role that enhanced protein O-GlcNAcylation plays in modulating the phenotype of cardiac fibroblasts (CF) is unknown. Read More

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Proteomic identification of mitochondrial targets of arginase in human breast cancer.

PLoS One 2013 5;8(11):e79242. Epub 2013 Nov 5.

Internal Medicine, Charles Drew University of Medicine and Science, Los Angeles, California, United States of America ; Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America ; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America.

We have previously reported arginase expression in human breast cancer cells and demonstrated that the inhibition of arginase by N(ω) hydroxy L-arginine (NOHA) in MDA-MB-468 cells induces apoptosis. However, arginase expression and its possible molecular targets in human breast tumor samples and potential clinical implications have not been fully elucidated. Here, we demonstrate arginase expression in human breast tumor samples, and several established breast cancer cell lines, in which NOHA treatment selectively inhibits cell proliferation. Read More

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Akita spontaneously type 1 diabetic mice exhibit elevated vascular arginase and impaired vascular endothelial and nitrergic function.

PLoS One 2013 19;8(8):e72277. Epub 2013 Aug 19.

Department of Pharmacology and Toxicology, Georgia Regents University, Augusta, Georgia, United States of America.

Background: Elevated arginase (Arg) activity is reported to be involved in diabetes-induced vascular endothelial dysfunction. It can reduce L-arginine availability to nitric oxide (NO) synthase (NOS) and NO production. Akita mice, a genetic non-obese type 1 diabetes model, recapitulate human diabetes. Read More

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January 2015

Post-exposure therapeutic efficacy of COX-2 inhibition against Burkholderia pseudomallei.

PLoS Negl Trop Dis 2013 9;7(5):e2212. Epub 2013 May 9.

Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, Louisiana, United States of America.

Burkholderia pseudomallei is a Gram-negative, facultative intracellular bacillus and the etiologic agent of melioidosis, a severe disease in Southeast Asia and Northern Australia. Like other multidrug-resistant pathogens, the inherent antibiotic resistance of B. pseudomallei impedes treatment and highlights the need for alternative therapeutic strategies that can circumvent antimicrobial resistance mechanisms. Read More

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November 2013

PRMT5 modulates the metabolic response to fasting signals.

Proc Natl Acad Sci U S A 2013 May 13;110(22):8870-5. Epub 2013 May 13.

The Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, CA 92037, USA.

Under fasting conditions, increases in circulating glucagon maintain glucose balance by promoting hepatic gluconeogenesis. Triggering of the cAMP pathway stimulates gluconeogenic gene expression through the PKA-mediated phosphorylation of the cAMP response element binding (CREB) protein and via the dephosphorylation of the latent cytoplasmic CREB regulated transcriptional coactivator 2 (CRTC2). CREB and CRTC2 activities are increased in insulin resistance, in which they promote hyperglycemia because of constitutive induction of the gluconeogenic program. Read More

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