A5010902028- Mitochondrial Function and Pathology
- Adipose Tissue and Metabolism
- Cardiac Ischemia and Reperfusion
- Biochemical Acid Research Studies
- Redox biology and oxidative stress
- Diet and metabolism studies
- Cardiovascular Function and Risk Factors
- Cancer, Hypoxia, and Metabolism
- Coenzyme Q10 studies and effects
- Antioxidant Activity and Oxidative Stress
- Endoplasmic Reticulum Stress and Disease
- Ubiquitin and proteasome pathways
- Metabolism and Genetic Disorders
- Alzheimer's disease research and treatments
- Diet, Metabolism, and Disease
- Metabolomics and Mass Spectrometry Studies
- Advanced Glycation End Products research
- ATP Synthase and ATPases Research
- Electron Spin Resonance Studies
- Congenital heart defects research
- Pancreatic function and diabetes
- Glutathione Transferases and Polymorphisms
- Tryptophan and brain disorders
- Eicosanoids and Hypertension Pharmacology
- Retinal Diseases and Treatments
The University of Texas Southwestern Medical Center
2008-2024
Southwestern Medical Center
2019-2021
Oklahoma Medical Research Foundation
2009-2018
University of Oklahoma Health Sciences Center
2010-2018
Case Western Reserve University
1998-2013
University of Iowa
2013
University of Oklahoma Medical Center
2006-2012
University of Oklahoma
2007-2010
Minneapolis Heart Institute Foundation
2008
University of Minnesota
2008
Glutamate transporters are involved in the maintenance of synaptic glutamate concentrations. Because its potential neurotoxicity, clearance from cleft may be critical for neuronal survival. Inhibition uptake synapse has been implicated several neurodegenerative disorders. In particular, is inhibited Alzheimer's disease (AD); however, mechanism decreased transporter activity unknown. Oxidative damage brain models neurodegeneration, as well AD. by oxidative reactive oxygen species and lipid...
Numerous degenerative disorders are associated with elevated levels of prooxidants and declines in mitochondrial aconitase activity. Deficiency the iron-binding protein frataxin results diminished activity various iron-sulfur proteins including aconitase. We found that can undergo reversible citrate-dependent modulation response to pro-oxidants. Frataxin interacted a fashion, reduced level oxidant-induced inactivation, converted inactive [3Fe-4S]1+ enzyme active [4Fe-4S]2+ form protein....
Chronic hyperglycemia causes structural alterations of proteins through the Maillard reaction. In diabetes, methylglyoxal (MGO)-induced hydroimidazolones are predominant modification. contrast to acute hyperglycemia, mitochondrial respiration is depressed in chronic diabetes. To determine whether MGO-derived protein modifications result abnormalities bioenergetics and superoxide formation, proteomics functional studies were performed renal cortical mitochondria isolated from rats with 2, 6,...
Tissue regenerative potential displays striking divergence across phylogeny and ontogeny, but the underlying mechanisms remain enigmatic. Loss of mammalian cardiac correlates with cardiomyocyte cell-cycle arrest polyploidization as well development postnatal endothermy. We reveal that diploid abundance 41 species conforms to Kleiber's law-the ¾-power law scaling metabolism bodyweight-and inversely standard metabolic rate, body temperature, serum thyroxine level. Inactivation thyroid hormone...
Ketogenic diets are high in fat and low carbohydrates as well protein which forces cells to rely on lipid oxidation mitochondrial respiration rather than glycolysis for energy metabolism. Cancer (relative normal cells) believed exist a state of chronic oxidative stress mediated by The current study tests the hypothesis that ketogenic enhance radio-chemo-therapy responses lung cancer xenografts enhancing stress.Mice bearing NCI-H292 A549 were fed diet (KetoCal 4:1 fats:...
Rationale: Heart failure with preserved ejection fraction (HFpEF) is a mortal clinical syndrome without effective therapies. We recently demonstrated in mice that combination of metabolic and hypertensive stress recapitulates key features human HFpEF. Objective: Using this novel preclinical HFpEF model, we set out to define manipulate dysregulations occurring myocardium. Methods Results: observed impairment mitochondrial fatty acid oxidation associated hyperacetylation enzymes the pathway....
During normal cellular metabolism, mitochondrial electron transport results in the formation of superoxide anion (O⨪<sub>2</sub>) and subsequently hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>). Because H<sub>2</sub>O<sub>2</sub> increases concentration under certain physiologic pathophysiologic conditions can oxidatively modify components, it is critical to understand response mitochondria H<sub>2</sub>O<sub>2</sub>. In present study, treatment isolated rat heart with resulted a decline...
Previous research has established that 4-hydroxy-2-nonenal (HNE), a highly toxic product of lipid peroxidation, is potent inhibitor mitochondrial respiration. HNE exerts its effects on respiration by inhibiting α-ketoglutarate dehydrogenase (KGDH). Because the central role KGDH in metabolism and emerging evidence free radicals contribute to dysfunction associated with numerous diseases, it great interest further characterize mechanism inhibition. In present study, treatment rat heart...
Restoration of blood flow to ischemic myocardial tissue results in an increase the production oxygen radicals. Highly reactive, free radical species have potential damage cellular components. Clearly, maintenance viability is dependent, part, on removal altered protein. The proteasome a major intracellular proteolytic system which degrades oxidized and ubiquitinated forms Utilizing <i>in vivo</i> rat model, we demonstrate that coronary occlusion/reperfusion resulted declines...
We report here the development of an immunochemical procedure that uses antibody specific to 4-hydroxynonenal (HNE) moiety for detection HNE-protein adducts. The HNE-specific was prepared by immunizing rabbits with a HNE-keyhole limpet hemocyanin conjugate and purifying rabbit serum on affinity gel covalent attachment HNE-conjugated heptapeptide. When various preparations glyceraldehyde-3-phosphate dehydrogenase containing 0-7.0 equivalent HNE-histidine residues per subunit were obtained...
Incubation of glucose-6-phosphate dehydrogenase (Glu-6-PDH) from Leuconostoc mesenteroides with the lipid peroxidation product 4-hydroxy-2-nonenal leads to formation cross-linked protein.This is accompanied by appearance protein-associated fluorescence excitation and emission maxima 340 415 nm, respectively, disappearance histidine lysine residues.Cross-linked protein less susceptible than native Glu-6-PDH proteolysis multicatalytic protease, a multienzymic proteolytic complex involved in...
Incubation of glucose-6-phosphate dehydrogenase from Leuconostoc mesenteroides with 4-hydroxy-2-nonenal (HNE) results in a pseudo first-order loss enzyme activity. The pH dependence the inactivation rate exhibits an inflection around 10, and is protected by glucose 6-phosphate. Loss activity corresponds formation one carbonyl function per subunit appearance lysine-HNE adduct. data presented this paper are consistent view that epsilon-amino group lysine residue 6-phosphate-binding site reacts...
© 1997 Federation of European Biochemical Societies.
Cardiac reperfusion and aging are associated with increased rates of mitochondrial free radical production. Mitochondria therefore a likely site reperfusion-induced oxidative damage, the severity which may increase age. 4-Hydroxy-2-nonenal (HNE), major product lipid peroxidation, increases in concentration upon ischemic cardiac tissue, can react inactivate enzymes, inhibits respiration vitro . HNE modification protein(s) might, therefore, be expected to occur during result loss function. In...
It has previously been reported that exposure of purified mitochondrial or cytoplasmic aconitase to superoxide (O2•) hydrogen peroxide (H2O2) leads release the Fe-α from enzyme's [4Fe−4S]2+ cluster and inactivation. Nevertheless, little is known regarding response pro-oxidants within intact mitochondria. In present study, we provide evidence rapidly inactivated subsequently reactivated when isolated cardiac mitochondria are treated with H2O2. Reactivation enzyme dependent on presence...
During the progression of certain degenerative conditions, including myocardial ischemia-reperfusion injury, mitochondria are a source increased free-radical generation and exhibit declines in respiratory function(s). It has therefore been suggested that oxidative damage to mitochondrial components plays critical role pathology these processes. Polyunsaturated fatty acids membrane lipids prime molecular targets damage. A major product lipid peroxidation, 4-hydroxy-2-nonenal (HNE), is highly...
In laboratory rodents, caloric restriction (CR) retards several age-dependent physiological and biochemical changes in skeletal muscle, including increased steady-state levels of oxidative damage to lipids, DNA, proteins. We used immunogold electron microscopic (EM) techniques with antibodies raised against 4-hydroxy-2-nonenal (HNE) -modified proteins, dinitrophenol, nitrotyrosine quantify localize the accrual rhesus monkey vastus lateralis muscle. Using EM analysis muscle from monkeys...
Giant cell arteritis (GCA) is a systemic vasculitis preferentially affecting large and medium-sized arteries. Inflammatory infiltrates in the arterial wall induce luminal occlusion with subsequent ischemia degradation of elastic membranes, allowing aneurysm formation. To identify pathways relevant to disease process, differential display–PCR was used. The enzyme aldose reductase (AR), which implicated regulation tissue osmolarity, found be upregulated arteritic lesions. Upregulated AR...
Heart attacks caused by occlusion of coronary arteries are often treated mechanical or enzymatic removal the and reperfusion ischemic heart. It is now recognized that per se contributes to myocardial damage, there a great interest in identifying molecular basis this damage. We recently showed inhibiting protein kinase Cdelta (PKCdelta) protects heart from ischemia reperfusion-induced Here, we demonstrate PKCdelta activity mitochondrial translocation at onset mediates apoptosis facilitating...
Obesity is a predictor of diabetes and cardiovascular disease. One consequence obesity dyslipidemia characterized by high blood triglycerides. It has been proposed that oxidative stress, driven utilization lipids for energy, contributes to these diseases. The effects stress are mitigated an endogenous antioxidant enzyme network, but little known about its response fat utilization. Our experiments used multiplexed quantitative proteomics method measure expression in heart tissue mouse model...