- Nitric Oxide and Endothelin Effects
- Hemoglobin structure and function
- Electron Spin Resonance Studies
- Cassava research and cyanide
- Metal-Catalyzed Oxygenation Mechanisms
- Sulfur Compounds in Biology
- Metal complexes synthesis and properties
- Heme Oxygenase-1 and Carbon Monoxide
- Trace Elements in Health
- Hematopoietic Stem Cell Transplantation
- Photosynthetic Processes and Mechanisms
- Neonatal Health and Biochemistry
- Mitochondrial Function and Pathology
- Porphyrin Metabolism and Disorders
- T-cell and B-cell Immunology
- Electrochemical Analysis and Applications
- Chronic Lymphocytic Leukemia Research
- Porphyrin and Phthalocyanine Chemistry
- Prenatal Substance Exposure Effects
- Eicosanoids and Hypertension Pharmacology
- Electrochemical sensors and biosensors
- Paraquat toxicity studies and treatments
- Cardiac Ischemia and Reperfusion
- Acute Myeloid Leukemia Research
- Vitamin C and Antioxidants Research
University of Pittsburgh
2012-2024
King's College Hospital
2004-2019
Cardiff University
2010-2011
Carnegie Mellon University
1998-2010
King's College Hospital NHS Foundation Trust
2008
King's College London
2007-2008
Duke University
2003
Aarhus University
2003
VA Pittsburgh Healthcare System
2001
University of Alabama
1998
Mitochondrial nitric oxide synthase (mtNOS), its cellular NOS isoform, and the effects of mitochondrially produced NO on bioenergetics have been controversial since mtNOS was first proposed in 1995. Here we functionally demonstrate presence a cardiac mitochondria. This accomplished by direct porphyrinic microsensor measurement Ca 2+ -dependent production individual mitochondria isolated from wild-type mouse hearts. could be inhibited antagonists or protonophore collapse mitochondrial...
Although the function of metallothionein (MT), a 6- to 7-kDa cysteine-rich metal binding protein, remains unclear, it has been suggested from in vitro studies that MT is an important component intracellular redox signaling, including being target for nitric oxide (NO). To directly study interaction between and NO live cells, we generated fusion protein consisting sandwiched two mutant green fluorescent proteins (GFPs). In with this chimera (FRET-MT) demonstrate resonance energy transfer...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDioxygen binding to diferrous centers. Models for diiron-oxo proteinsYanhong Dong, Stephane Menage, Bridget A. Brennan, Timothy E. Elgren, Ho G. Jang, Linda L. Pearce, and Lawrence Que Jr.Cite this: J. Am. Chem. Soc. 1993, 115, 5, 1851–1859Publication Date (Print):March 1, 1993Publication History Published online1 May 2002Published inissue 1 March 1993https://pubs.acs.org/doi/10.1021/ja00058a033https://doi.org/10.1021/ja00058a033research-articleACS...
Stimulation of cardiomyocytes to endogenously evolve nitric oxide is shown by microsensor measurements on single cells lead transient concentrations a few hundred nanomolar. At these submicromolar concentrations, no evidence could be found for the expected reaction between generated and oxymyoglobin present in cells: + → nitrate metmyoglobin. No metmyoglobin formation was detected electron paramagnetic resonance spectroscopy, revealed near quantitative conversion nitrite rather than ion....
Nitric oxide (NO) is shown to overcome the cyanide inhibition of cytochrome c oxidase in presence excess ferrocytochrome and oxygen. Addition NO partially reduced cyanide-inhibited form bovine enzyme by electron paramagnetic resonance spectroscopy result substitution at ferriheme a3 with reduction heme. The resulting nitrosylferroheme a 5-coordinate structure, proximal bond histidine having been broken. does not simply act as reversibly bound competitive inhibitor but an auxiliary substrate...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTElectrochemical, kinetic, and circular dichroic consequences of mutations at position 82 yeast iso-1-cytochrome cSteven P. Rafferty, Linda L. Pearce, Paul D. Barker, J. Guy Guillemette, Cyril M. Kay, Michael Smith, A. Grant MaukCite this: Biochemistry 1990, 29, 40, 9365–9369Publication Date (Print):October 1, 1990Publication History Published online1 May 2002Published inissue 1 October...
The possible influence of residue Phe-82 in the cytochrome c alkaline isomerization has been evaluated by spectrophotometric pH titrations a family mutant yeast iso-1-cytochromes which identity at this position varied. pKa for exchange Met-80 heme iron ligand was determined from S----Fe charge-transfer band (695 nm) monitored and found to be 8.5 wild type, 7.7 Ser-82, Gly-82, 7.2 Leu-82, Ile-82. pH-jump experiments [Davis et al. (1974) J. Biol. Chem. 249, 2624] established that substitutions...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAn EXAFS study of the interaction substrate with ferric active site protocatechuate 3,4-dioxygenaseAnne E. True, Allen M. Orville, Linda L. Pearce, John D. Lipscomb, and Lawrence Que, Jr.Cite this: Biochemistry 1990, 29, 48, 10847–10854Publication Date (Print):December 4, 1990Publication History Published online1 May 2002Published inissue 4 December 1990https://doi.org/10.1021/bi00500a019RIGHTS & PERMISSIONSArticle...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTProton NMR probes of the binuclear iron cluster in hemerythrinMichael J. Maroney, Donald M. Kurtz, Judith Nocek, Linda L. Pearce, and Lawrence. QueCite this: Am. Chem. Soc. 1986, 108, 22, 6871–6879Publication Date (Print):October 1, 1986Publication History Published online1 May 2002Published inissue 1 October 1986https://pubs.acs.org/doi/10.1021/ja00282a005https://doi.org/10.1021/ja00282a005research-articleACS PublicationsRequest reuse...
Silicosis is a lethal pneumoconiosis for which no therapy available. global threat, and more than 2.2 million people per year are exposed to silica in the United States. The initial response mediated by innate immunity. Phagocytosis of particles macrophages followed recruitment mitochondria phagosomes, generation mitochondrial reactive oxygen species, cytokine (IL-1β, TNF-α, IFN-β) release. In contrast with LPS, metabolic remodeling silica-exposed unclear. This study contrasts alterations...
The existence of mitochondrial nitric oxide (NO) synthase (mtNOS) has been controversial since it was first reported in 1995. We have addressed this issue by making direct microsensor measurements NO production the mitochondria isolated from mouse hearts. Mitochondrial stimulated Ca 2+ and inhibited blocking electrogenic uptake or using NOS antagonists. Cardiac mtNOS identified as neuronal isoform absence mice lacking but not endothelial inducible isoforms. In cardiomyocytes...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSpectroscopic and electrochemical properties of (.mu.-oxo)diiron(III) complexes related to diiron-oxo proteins. Structure [Fe2O(TPA)2(MoO4)](ClO4)2Richard C. Holz, Timothy E. Elgren, Linda L. Pearce, Jian H. Zhang, Charles J. O'Connor, Lawrence Que Jr.Cite this: Inorg. Chem. 1993, 32, 25, 5844–5850Publication Date (Print):December 1, 1993Publication History Published online1 May 2002Published inissue 1 December...
Epperly, M. W., Melendez, J. A., Zhang, X., Nie, S, Pearce, L., Peterson, J., Franicola, D., Dixon, T., Greenberger, B. Komanduri, P., Wang, H. and S. Mitochondrial Targeting of a Catalase Transgene Product by Plasmid Liposomes Increases Radioresistance In Vitro Vivo. Radiat. Res. 171, 588-595 (2009).To determine whether increased mitochondrially localized catalase was radioprotective, human transgene cloned into small pSVZeo plasmid to the mitochondria 32D cl 3 cells adding mitochondrial...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTReduction of the binuclear iron site in octameric methemerythrins. Characterizations intermediates and a unifying reaction schemeLinda L. Pearce, Donald M. Kurtz Jr., Yao Min Xia, Peter G. DebrunnerCite this: J. Am. Chem. Soc. 1987, 109, 24, 7286–7293Publication Date (Print):November 1, 1987Publication History Published online1 May 2002Published inissue 1 November...
Sodium nitrite alone is shown to ameliorate sublethal cyanide toxicity in mice when given from ∼1 h before until 20 min after the toxic dose as demonstrated by recovery of righting ability. An optimum (12 mg/kg) was determined significantly relieve (5.0 administered intraperitoneally. Nitrite so rapidly produce NO bloodsteam judged dose-dependent appearance EPR signals attributable nitrosylhemoglobin and methemoglobin. It argued that antagonism inhibition cytochrome c oxidase crucial...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMultifield saturation magnetization and multifrequency EPR measurements of deoxyhemerythrin azide. A unified pictureMichael P. Hendrich, Linda L. Pearce, Lawrence Que Jr., N. Dennis Chasteen, Edmund DayCite this: J. Am. Chem. Soc. 1991, 113, 8, 3039–3044Publication Date (Print):April 1, 1991Publication History Published online1 May 2002Published inissue 1 April...
Background A variety of immune pathways can lead to graft-versus-host disease. better understanding the type response causing disease in defined clinical hematopoietic stem cell transplant settings is required inform development methods for monitoring patients and providing them tailored care.Design Methods Twenty-five were recruited presenting with myeloid malignancies treated a reduced intensity conditioning regimen prophylaxis comprising vivo lymphocyte depletion alemtuzumab cyclosporin....
Non-steroidal anti-inflammatory drugs have been shown to induce apoptosis in primary B-cell chronic lymphocytic leukaemia (CLL) cells, but the molecular mechanisms that underpin this observation not fully elucidated. Here, we analysed effect two novel aspirin analogues, 2-hydroxy benzoate zinc (2HBZ) and 4-hydroxy (4HBZ), on CLL samples.Cytotoxic effects of 2HBZ 4HBZ were cells derived from 52 patients, normal B- T-lymphocytes. Mechanisms action these agents also elucidated.Both analogues...
The primary response of proliferating bovine pulmonary artery endothelial cells (BPAECs) after X-ray irradiation [≤10 gray (Gy)] is shown to be transient cell-cycle arrest. Accompanying oxidant-linked functional changes within the mitochondria are readily measured, but increased autophagy not. Radiation-induced apoptosis negligible in this line—important because undergoing release oxygen-derived species that can overwhelm/mask radiation-associated and their effects we wish investigate. Cells...
There do not appear to be any established therapeutics for treating azide poisoning at this time, and presently available antidotes cyanide are far from ideal, being particularly impractical use if multiple victims present. The cobalt (II/III) complex of the Schiff-base ligand <i>trans</i>-[14]-diene (5,7,7,12,14,14-hexamethyl-1,4,8,11-tetraazacyclotetradeca-4,11-diene (CoN<sub>4</sub>[14]) is shown act as an effective antidote both toxicity in mice. Groups animals challenged with...