A5103228418- Selenium in Biological Systems
- Medical and Biological Ozone Research
- Trace Elements in Health
- Inflammatory mediators and NSAID effects
- Peroxisome Proliferator-Activated Receptors
- Erythrocyte Function and Pathophysiology
- Genomics, phytochemicals, and oxidative stress
- Heme Oxygenase-1 and Carbon Monoxide
- Eicosanoids and Hypertension Pharmacology
- Glutathione Transferases and Polymorphisms
- Birth, Development, and Health
- Estrogen and related hormone effects
- Hemoglobinopathies and Related Disorders
- Iron Metabolism and Disorders
- Redox biology and oxidative stress
- Cassava research and cyanide
- Fatty Acid Research and Health
- Paraoxonase enzyme and polymorphisms
- Acute Myeloid Leukemia Research
- Immune Response and Inflammation
- Pesticide Exposure and Toxicity
- HIV/AIDS drug development and treatment
- Heavy Metal Exposure and Toxicity
- Phagocytosis and Immune Regulation
- Metal-Catalyzed Oxygenation Mechanisms
Pennsylvania State University
2015-2024
Max Planck Institute for Biology of Ageing
2024
Center for Molecular Medicine and Immunology
2017-2023
University of Veterinary Science
2017-2023
Park University
2018-2019
Cancer Institute (WIA)
2018
Rice University
2015
Office of Infectious Diseases
2010
Vittal Mallya Scientific Research Foundation
1996-2000
The human genome contains 25 genes coding for selenocysteine-containing proteins (selenoproteins). These are involved in a variety of functions, most notably redox homeostasis. Selenoprotein enzymes with known functions designated according to these functions: TXNRD1, TXNRD2, and TXNRD3 (thioredoxin reductases), GPX1, GPX2, GPX3, GPX4, GPX6 (glutathione peroxidases), DIO1, DIO2, DIO3 (iodothyronine deiodinases), MSRB1 (methionine sulfoxide reductase B1), SEPHS2 (selenophosphate synthetase...
Selenium is an essential micronutrient that suppresses the redox-sensitive transcription factor NF-κB-dependent pro-inflammatory gene expression. To understand molecular mechanisms underlying anti-inflammatory property of selenium, we examined activity a key kinase NF-κB cascade, IκB-kinase β (IKKβ) subunit, as function cellular selenium status in murine primary bone marrow-derived macrophages and RAW264.7 macrophage-like cell line. In vitro assays revealed supplementation decreased IKKβ...
Selenium (Se) is an important element required for the optimal functioning of immune system. Particularly in macrophages, which play a pivotal role regulation, Se acts as major antioxidant form selenoproteins to mitigate cytotoxic effects reactive oxygen species. Here we describe anti-inflammatory agent and its effect on macrophage signal transduction pathways elicited by bacterial endotoxin, LPS. Our studies demonstrate that supplementation macrophages (Se-deficient) leads significant...
The inducible isoform of nitric oxide synthase (iNOS) is implicated in atherosclerosis, malignancy, rheumatoid arthritis, tissue and reperfusion injuries. A key determinant the pro-oxidant versus protective effects NO underlying redox status tissue. Selenoproteins, such as glutathione peroxidases (GPxs) thioredoxin reductases, are components cellular defence promote optimal antioxidant/oxidant balance. In this study, we have investigated relationship between Se status, iNOS expression...
myo -Inositol oxygenase (MIOX) activates O 2 at a mixed-valent nonheme diiron(II/III) cluster to effect oxidation of its cyclohexan-(1,2,3,4,5,6-hexa)-ol substrate [ -inositol (MI)] by four electrons d -glucuronate. Abstraction hydrogen from C 1 formally (superoxo)diiron(III/III) intermediate was previously proposed. Use deuterium-labeled substrate, 1,2,3,4,5,6-[ H] 6 -MI (D -MI), has now permitted initial characterization the C–H-cleaving intermediate. The MIOX·1,2,3,4,5,6-[ complex reacts...
The plasticity of macrophages is evident from their dual role in inflammation and resolution that are accompanied by changes the transcriptome metabolome. Along these lines, we have previously demonstrated micronutrient selenium increases macrophage production arachidonic acid (AA)-derived anti-inflammatory 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) decreases proinflammatory PGE2. Here, hypothesized modulated metabolism AA a differential regulation various prostaglandin (PG) synthases...
Inflammation is a hallmark of inflammatory bowel disease (IBD) that involves macrophages. Given the inverse link between selenium (Se) status and IBD-induced inflammation, our objective was to demonstrate selenoproteins in macrophages were essential suppress proinflammatory mediators, part, by modulation arachidonic acid metabolism. Acute colitis induced using 4% dextran sodium sulfate wild-type mice maintained on Se-deficient (<0.01 ppm Se), Se-adequate (0.08 ppm; selenite), two...
The survival rate for breast cancer drops dramatically once the disease progresses to metastatic stage. Selenium (Se) is an essential micronutrient credited with having high anticancer and chemopreventive properties. In our study, we investigated if dietary Se supplementation modified development in vivo. Three diets supplemented sodium selenite, methylseleninic acid (MSA) or selenomethionine (SeMet), as well a Se-deficient Se-adequate diet were fed mice before mammary gland inoculation of...
Erythrophagocytosis and the production of proinflammatory cytokines promote stress erythropoiesis during inflammation.
Epidemiological studies suggest a correlation between severity of acquired immunodeficiency syndrome (AIDS) and selenium deficiency, indicating protective role for this anti-oxidant during HIV infection. Here we demonstrate that thioredoxin reductase-1 (TR1), selenium-containing pyridine nucleotide-disulfide oxidoreductase reduces protein disulfides to free thiols, negatively regulates the activity HIV-1 encoded transcriptional activator, Tat, in human macrophages. We used small interfering...
The human constitutive androstane receptor (CAR, CAR1) regulates the expression of genes involved in xenobiotic metabolism liver. <i>CAR</i> gene uses multiple alternative splicing events during pre-mRNA processing, thereby enhancing CAR transcriptome. Previous reports have identified two prominent variants, CAR2 and CAR3, that possess four- five-amino acid insertions their ligand binding domains, respectively. Unlike constitutively active reference form receptor, we now demonstrate is a...
Breast cancer frequently metastasizes to the skeleton resulting in bone degradation due osteoclast activation. Metastases also downregulate differentiation and bone-rebuilding function of osteoblasts. Moreover, cells trigger osteoblast inflammatory stress responses. Pro-inflammatory mediators such as interleukin (IL)-6, monocyte chemoattractant protein-1 (MCP-1), cyclooxygenase-2 (COX-2) inducible nitric oxide synthase (iNOS), expressed by osteoblasts (MC3T3-E1) stimulated with human breast...
There is an increased risk of colon cancer associated with inflammatory bowel disease (IBD). Dietary fibers (DFs) naturally present in vegetables and whole grains offer numerous beneficial effects on intestinal health. However, the refined DFs health remain unclear. Therefore, we elucidated impact DF inulin colonic inflammation tumorigenesis.Four-week-old wild-type (WT) mice were fed diets containing insoluble cellulose (control) or for 4 weeks. A subgroup was then switched to drinking water...