A5021861465- Nitric Oxide and Endothelin Effects
- Hemoglobin structure and function
- Neuroscience and Neuropharmacology Research
- Electron Spin Resonance Studies
- Electrochemical sensors and biosensors
- Erythrocyte Function and Pathophysiology
- Hemoglobinopathies and Related Disorders
- Photosynthetic Processes and Mechanisms
- Receptor Mechanisms and Signaling
- Eicosanoids and Hypertension Pharmacology
- Photoreceptor and optogenetics research
- Ion channel regulation and function
- Molecular Sensors and Ion Detection
- Heme Oxygenase-1 and Carbon Monoxide
- Analytical Chemistry and Sensors
- Neonatal Health and Biochemistry
- Metal-Catalyzed Oxygenation Mechanisms
- Lipid Membrane Structure and Behavior
- Advanced Nanomaterials in Catalysis
- Electrochemical Analysis and Applications
- Mitochondrial Function and Pathology
- Carbon Nanotubes in Composites
- Sphingolipid Metabolism and Signaling
- Drug Transport and Resistance Mechanisms
- Photochemistry and Electron Transfer Studies
The University of Texas Health Science Center at Houston
2015-2024
The University of Texas at Austin
1996-2013
École Polytechnique
2007
Inserm
2007
Centre National de la Recherche Scientifique
2007
Institute for Molecular Medicine
2007
Université de Rennes
2007
University of Nottingham
2004
Michigan State University
2002
New York University
2002
It has been previously shown that besides synthesizing nitric oxide (NO), neuronal and inducible NO synthase (NOS) generates superoxide (O⨪2) under conditions ofl-arginine depletion. However, there is controversy regarding whether endothelial NOS (eNOS) can also produce O⨪2. Moreover, the mechanism control of this process are not fully understood. Therefore, we performed electron paramagnetic resonance spin-trapping experiments to directly measure characterize O⨪2 generation from purified...
Many diseases are associated with oxidative stress, which occurs when the production of reactive oxygen species (ROS) overwhelms scavenging ability an organism. Here, we evaluated carbon nanoparticle antioxidant properties poly(ethylene glycolated) hydrophilic clusters (PEG-HCCs) by electron paramagnetic resonance (EPR) spectroscopy, electrode, and spectrophotometric assays. These nanoparticles have 1 equivalent stable radical showed superoxide (O2 (•-)) dismutase-like yet were inert to...
Nitric oxide (NO) is extremely toxic to Clostridium botulinum , but its molecular targets are unknown. Here, we identify a heme protein sensor (SONO) that displays femtomolar affinity for NO. The crystal structure of the SONO domain reveals previously undescribed fold and strategically placed tyrosine residue modulates heme-nitrosyl coordination. Furthermore, architecture ortholog cloned from Chlamydomonas reinhardtii indicates NO signaling through cyclic guanosine monophosphate arose before...
Sphingosine-1-phosphate (S1P) is a bioactive lipid that regulates multicellular functions through interactions with its receptors on cell surfaces. S1P enriched and stored in erythrocytes; however, it not clear whether alterations are involved the prevalent debilitating hemolytic disorder sickle disease (SCD). Here, using metabolomic screening, we found highly elevated blood of mice humans SCD. In murine models SCD, demonstrated erythrocyte sphingosine kinase 1 (SPHK1) underlies sickling...
Endothelial nitric oxide synthase (eNOS) is an important regulator of vascular and cardiac function. Peroxynitrite (ONOO(-)) inactivates eNOS, but questions remain regarding the mechanisms this process. It has been reported that inactivation due to oxidation eNOS zinc-thiolate cluster, rather than cofactor tetrahydrobiopterin (BH(4)); however, remains highly controversial. Therefore, we investigated ONOO(-)-induced dysfunction their dose dependence. Exposure human ONOO(-) resulted in a...
Selectivity among NO, CO, and O₂ is crucial for the physiological function of most heme proteins. Although there a million-fold variation in equilibrium dissociation constants (K(D)), ratios NO:CO:O₂ binding stay roughly same, 1:~10(3):~10(6), when proximal ligand histidine distal site apolar. For these proteins, "sliding scale rule" plots log(K(D)) versus type that allows predictions K(D) values if one or two are missing. The predicted O₂to Ns H-NOX coincides with value determined...
Graphene quantum dots (GQDs) have recently been employed in various fields including medicine as antioxidants, primarily because of favorable biocompatibility comparison to common inorganic dots, although the structural features that lead biological activities GQDs are poorly understood. Here, we report coal-derived and their poly(ethylene glycol)-functionalized derivatives serve efficient evaluate electrochemical, chemical, vitro activities.
Moyamoya disease ( MMD ) is a progressive vasculopathy characterized by occlusion of the terminal portion internal carotid arteries and its branches, formation compensatory moyamoya collateral vessels. Homozygous mutations in GUCY1A3 have been reported as cause achalasia. Probands n = 96) from unrelated families underwent sequencing . Functional studies were performed to confirm pathogenicity identified variants. Two affected individuals found compound heterozygous MM041 was diagnosed with...
Here we show that the active portion of a graphitic nanoparticle can be mimicked by perylene diimide (PDI) to explain otherwise elusive biological and electrocatalytic activity construct. Development molecular analogues mimic antioxidant properties oxidized graphenes, in this case poly(ethylene glycolated) hydrophilic carbon clusters (PEG–HCCs), will afford important insights into highly efficient PEG–HCCs their analogues. PEGylated diimides (PEGn–PDI) serve as well-defined graphenes...
The superoxide dismutase-like activity of poly(ethylene glycolated) hydrophilic carbon clusters (PEG-HCCs), anthracite and bituminous graphene quantum dots (PEG-aGQDs PEG-bGQDs, respectively), two fullerene nanozymes, tris malonyl-C60 (C3) polyhydroxylated-C60 (C60-OHn), were compared using direct optical stopped-flow kinetic measurements, together with three native dismutases (SODs), CuZnSOD, MnSOD, FeSOD, at both pH 12.7 8.5. Computer modeling including SOD catalytic steps self-dismutation...
Although soluble guanylyl cyclase (sGC) functions in an environment which O(2), NO, and CO are potential ligands for its heme moiety, the enzyme displays a high affinity only physiological ligand, but has limited no O(2). Recent studies of truncated version sGC beta(1)-subunit containing heme-binding domain (Boon, E. M., Huang, S H., Marletta, M. A. (2005) Nat. Chem. Biol., 1, 53-59) showed that introduction hydrogen-bonding tyrosine into distal pocket changes ligand specificity moiety...
Soluble guanylyl cyclase (sGC), the key enzyme for formation of second messenger cyclic GMP, is an authentic sensor nitric oxide (NO). Binding NO to sGC leads strong activation activity. Multiple molecules and steps binding have been implicated, but target detailed mechanism remain controversial. In this study, we used (15)NO (14)NO anaerobic sequential mixing-freeze-quench electron paramagnetic resonance unambiguously confirm that heme Fe NO. The linear dependence on concentration up 600...
Elevated sphingosine 1-phosphate (S1P) is detrimental in Sickle Cell Disease (SCD), but the mechanistic basis remains obscure. Here, we report that increased erythrocyte S1P binds to deoxygenated sickle Hb (deoxyHbS), facilitates deoxyHbS anchoring membrane, induces release of membrane-bound glycolytic enzymes and turn switches glucose flux towards glycolysis relative pentose phosphate pathway (PPP). Suppressed PPP causes compromised glutathione homeostasis oxidative stress, while enhanced...
Hydrophilic carbon clusters (HCCs) are oxidized nanoparticles with a high affinity for electrons. The electron accepting strength of HCCs, employing the efficient conversion superoxide (O2•–) to molecular oxygen (O2) via single-electron oxidation, was monitored using cyclic voltammetry and paramagnetic resonance spectroscopy. We found that HCCs possess O2 reduction reaction (ORR) capabilities through two-electron process formation H2O2. By comparing results from aprotic solvents those...
Introduction: While oxidative stress can be measured during transient cerebral ischemia, antioxidant therapies for ischemic stroke have been clinically unsuccessful. Many antioxidants are limited in their range and/or capacity quenching radicals and generate toxic intermediates overwhelming depleted endogenous protection. We developed a new class, 40 × 2 nm carbon nanoparticles, hydrophilic clusters, conjugated to poly(ethylene glycol) termed PEG-HCCs. These particles high superoxide...
A baculovirus system was used to express the oxygenase and reductase domains of human endothelial nitric-oxide synthase (ecNOS) as distinct proteins. The domain (residues 1–491) expressed using a vector containing His6 tag at N terminus. purified had an apparent molecular mass ∼54 kDa, retained ability bind L-arginine form ferrous CO complex. 492-1244) ∼82 kDa catalyze NADPH-dependent cytochrome c reduction, which enhanced 10-fold by presence Ca2+/calmodulin. Both exhibited immunoreactivity...
STEAP1, six-transmembrane epithelial antigen of prostate member 1, is strongly expressed in several types cancer cells, particularly cancer, and inhibition its expression reduces the rate tumor cell proliferation. However, physiological function STEAP1 remains unknown. Here for first time, we purified a mammalian (rabbit) at milligram level, permitting high-quality biochemical biophysical characterizations. We found that likely assembles as homotrimer forms heterotrimer when co-expressed...
Allostery can be manifested as a combination of repression and activation in multidomain proteins allowing for fine tuning regulatory mechanisms. Here we have used single molecule fluorescence resonance energy transfer (smFRET) molecular dynamics simulations to study the mechanism allostery underlying negative cooperativity between two agonists glutamate glycine NMDA receptor. These data show that binding one agonist leads conformational flexibility an increase spread at second site....
Delta receptors are members of the ionotropic glutamate receptor superfamily and form trans-synaptic connections by interacting with extracellular scaffolding protein cerebellin-1 presynaptic transmembrane neurexin-1β. Unlike other family members, however, direct agonist-gated ion channel activity has not been recorded in delta receptors. Here, we show that GluD2 subtype forms cation-selective channels when bound to Using fluorescence lifetime measurements chemical cross-linking, reveal...
Endothelial nitric-oxide synthase (eNOS) plays important roles in vascular physiology and homeostasis. Whether eNOS catalyzes nitric oxide biosynthesis or the synthesis of reactive oxygen species such as superoxide, hydrogen peroxide, peroxynitrite is dictated by bioavailability tetrahydrobiopterin (BH(4)) L-arginine during catalysis. The effect BH(4) on oxygen-induced radical intermediates has been investigated single turnover rapid-freeze quench EPR spectroscopy using isolated oxygenase...
Fast excitatory synaptic transmission in the mammalian central nervous system is mediated by glutamate-activated α-amino-5-methyl-3-hydroxy-4-isoxazole propionate (AMPA) receptors. In neurons, AMPA receptors coassemble with transmembrane receptor regulatory proteins (TARPs). Assembly TARP γ8 alters biophysical properties of receptor, producing resensitization currents continued presence glutamate. Using single-channel recordings, we show that under resensitizing conditions, GluA2 primarily...