A5007066761- Nitric Oxide and Endothelin Effects
- Mitochondrial Function and Pathology
- Cardiovascular and exercise physiology
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Redox biology and oxidative stress
- Iron Metabolism and Disorders
- Trace Elements in Health
- Metabolism and Genetic Disorders
- Peroxisome Proliferator-Activated Receptors
- Cardiovascular Function and Risk Factors
- Cancer, Hypoxia, and Metabolism
- Neuroscience and Neuropharmacology Research
- Sulfur Compounds in Biology
- Cardiac Ischemia and Reperfusion
- Hemoglobinopathies and Related Disorders
- Adipose Tissue and Metabolism
- Diet and metabolism studies
- Alzheimer's disease research and treatments
- Renin-Angiotensin System Studies
- Heart Failure Treatment and Management
- Antioxidant Activity and Oxidative Stress
- Tryptophan and brain disorders
- Cell death mechanisms and regulation
- Peptidase Inhibition and Analysis
- Vitamin C and Antioxidants Research
University of Ioannina
2003-2025
University of Pennsylvania
2012-2024
Children's Hospital of Philadelphia
2013-2024
Translational Therapeutics (United States)
2015-2018
Hospital of the University of Pennsylvania
2014-2016
Kansas State University
2014-2016
Rowan University
2016
Harvard University
2015
Massachusetts General Hospital
2015
Brigham and Women's Hospital
2015
Innate and adaptive defense mechanisms protect the respiratory system from attack by microbes. Here, we present evidence that bitter taste receptor T2R38 regulates mucosal innate of human upper airway. Utilizing immunofluorescent live cell imaging techniques in polarized primary sinonasal cells, demonstrate is expressed epithelium activated response to acyl-homoserine lactone quorum-sensing molecules secreted Pseudomonas aeruginosa other gram-negative bacteria. Receptor activation...
Background— Inorganic nitrate (NO 3 − ), abundant in certain vegetables, is converted to nitrite by bacteria the oral cavity. Nitrite can be nitric oxide setting of hypoxia. We tested hypothesis that NO supplementation improves exercise capacity heart failure with preserved ejection fraction via specific adaptations exercise. Methods and Results— Seventeen subjects participated this randomized, double-blind, crossover study comparing a single dose -rich beetroot juice , 12.9 mmol) an...
S -nitrosylation increases the catalytic efficiency of an enzyme critical to fatty acid β-oxidation.
Overnutrition disrupts circadian metabolic rhythms by mechanisms that are not well understood. Here, we show diet-induced obesity (DIO) causes massive remodeling of enhancer activity in mouse liver, triggering synchronous high-amplitude both fatty acid (FA) synthesis and oxidation. SREBP expression was rhythmically induced DIO, leading to FA and, surprisingly, oxidation (FAO). DIO similarly caused a rhythm PPARα, which also required for FAO. Provision pharmacological activator PPARα...
S-nitrosylation, the selective posttranslational modification of protein cysteine residues to form S-nitrosocysteine, is one molecular mechanisms by which nitric oxide influences diverse biological functions. In this study, unique MS-based proteomic approaches precisely pinpointed site S-nitrosylation in 328 peptides 192 proteins endogenously modified WT mouse liver. Structural analyses revealed that S-nitrosylated were equally distributed hydrophobic and hydrophilic areas with an average...
Genetic variants at the solute carrier family 39 member 8 (SLC39A8) gene locus are associated with regulation of whole-blood manganese (Mn) and multiple physiological traits. SLC39A8 encodes ZIP8, a divalent metal ion transporter best known for zinc transport. Here, we hypothesized that ZIP8 regulates Mn homeostasis Mn-dependent enzymes to influence metabolism. We generated Slc39a8-inducible global-knockout (ZIP8-iKO) liver-specific-knockout (ZIP8-LSKO) mice observed markedly decreased...
Protein S-nitrosylation controls the brain’s use of glutamate for energy or neurotransmission.
Abstract In Alzheimer's disease (AD), dysfunctional mitochondrial metabolism is associated with synaptic loss, the major pathological correlate of cognitive decline. Mechanistic insight for this relationship, however, still lacking. Here, comparing isogenic wild‐type and AD mutant human induced pluripotent stem cell (hiPSC)‐derived cerebrocortical neurons (hiN), evidence found compromised energy in using Seahorse platform to analyze glycolysis oxidative phosphorylation (OXPHOS)....
The calcein-AM (calcein-acetoxymethyl ester) method is a widely used technique that supposed to assay the intracellular ‘labile iron pool’ (LIP). When cells in culture are exposed this ester, it passes plasma membrane and reacts with cytosolic unspecific esterases. One of reaction products, calcein, fluorochrome hydrophilic alcohol which membranes non-permeable which, consequently, retained within cytosol cells. Calcein fluorescence quenched following chelation low-mass labile iron, degree...
Rationale: The regulation of calcium (Ca 2+ ) homeostasis by β-adrenergic receptor (βAR) activation provides the essential underpinnings sympathetic myocardial function, as well a basis for understanding molecular events that result in hypertrophic signaling and heart failure. Sympathetic stimulation βAR not only induces protein phosphorylation but also activates nitric oxide–dependent signaling, which modulates cardiac contractility. Nonetheless, role oxide βAR-dependent Ca handling has yet...
The placenta is metabolically active and supports the growth of fetus. We hypothesize that deficits in capacity to maintain bioenergetic metabolic stability during pregnancy may result spontaneous preterm birth (SPTB). To explore this hypothesis, we performed a nested cased control study metabolomic signatures placentas from women with SPTB (<36 weeks gestation) compared normal pregnancies (≥38 gestation). for effects gestational age on metabolism, also studied subset metabolites...
Jurkat cells in culture were exposed to oxidative stress the form of continuously generated hydrogen peroxide, obtained by addition glucose oxidase medium. This treatment induced a rapid, dose-dependent increase ICIP (intracellular calcein-chelatable iron pool). Early destabilization lysosomal membranes and subsequent nuclear DNA strand breaks also observed, as evaluated Acridine Orange relocation test comet assay respectively. Somewhat later, these effects followed lowered mitochondrial...
In search for compounds, able to protect nuclear DNA in cells exposed oxidative stress, extracts from olive leaves, fruits, oil and mill waste water were tested by using the "single cell gel electrophoresis" methodology (comet assay). Jurkat culture continuously generated hydrogen peroxide (11.8±1.5 μM per min) direct addition into growth medium of appropriate amount enzyme "glucose oxidase" presence or absence total extracts. The protective effects isolated compounds evaluated their ability...
We show that thiols in the 4-cysteine zinc-finger motif of DksA, an RNA polymerase accessory protein known to regulate stringent response, sense oxidative and nitrosative stress. Hydrogen peroxide- or nitric oxide (NO)-mediated modifications DksA release metal cofactor drive reversible changes α-helicity protein. Wild-type relA spoT mutant Salmonella, but not isogenic dksA-deficient bacteria, experience downregulation r-protein amino acid transport expression after NO treatment, suggesting...
Nitric oxide (NO) mediates a substantial part of its physiologic functions via S-nitrosylation, however the cellular substrates for NO-mediated S-nitrosylation are largely unknown. Here we describe S-nitrosoproteome using high-density protein microarray chip containing 16,368 unique human proteins. We identified 834 potentially S-nitrosylated Using and highly specific labeling affinity capture proteins, 138 cysteine residues on 131 peptides in 95 proteins were determined, defining critical...
Nitrate-rich beetroot juice has been shown to improve exercise capacity in heart failure with preserved ejection fraction, but studies using pharmacological preparations of inorganic nitrate are lacking.To determine (1) the dose-response effect potassium (KNO3) on capacity; (2) population-specific pharmacokinetic and safety profile KNO3 fraction.We randomized 12 subjects fraction oral (n=9) or chloride (n=3). Subjects received 6 mmol twice daily during week 1, followed by thrice 2. Supine...
<ns4:p>Nitric oxide is an endogenously formed gas that acts as a signaling molecule in the human body. The functions of nitric are accomplished through two primer mechanisms: cGMP-mediated phosphorylation and formation S-nitrosocysteine on proteins. This review presents discusses previous more recent findings documenting regulates metabolic activity. These discussions primarily focus endothelial synthase (eNOS) source oxide.</ns4:p>
Abstract NO is critical to immunity, but its role in the development of immune system unknown. In this study, we show that S-nitrosoglutathione reductase (GSNOR), a protein key control S-nitrosylation, important for lymphocytes. Genetic deletion GSNOR mice results significant decrease both T and B lymphocytes periphery. thymus, deficiency causes excessive increases apoptosis, reduces number CD4 single-positive thymocytes. Lymphopenia increase S-nitrosylation apoptosis GSNOR-deficient are...
Several lines of evidence support a pathophysiological role immunity in atherosclerosis. Tyrosine-nitrated proteins, footprint oxygen- and nitrogen-derived oxidants generated by cells the immune system, are enriched atheromatous lesions circulation patients with coronary artery disease (CAD). However, consequences possible reactions triggered presence nitrated proteins subjects clinically documented atherosclerosis have not been explored.Specific immunoglobulins that recognize...
Background Stable plasma nitric oxide ( NO ) metabolites M ), composed predominantly of nitrate and nitrite, are attractive biomarkers bioavailability. levels integrate the influence ‐synthase‐derived production/metabolism, dietary intake inorganic nitrate/nitrite, clearance . Furthermore, most abundant , can be reduced to via nitrate‐nitrite‐ pathway. Methods Results We compared serum among subjects without heart failure (n=126), with preserved ejection fraction HF p EF ; n=43), r n=32). LV...