A5001974475- Advanced Glycation End Products research
- Chronic Kidney Disease and Diabetes
- Cell Adhesion Molecules Research
- Alcohol Consumption and Health Effects
- Bone health and osteoporosis research
- Enzyme Structure and Function
- Natural Antidiabetic Agents Studies
- Protein Structure and Dynamics
- Metabolomics and Mass Spectrometry Studies
- Heat shock proteins research
- Bone health and treatments
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Renal Diseases and Glomerulopathies
- S100 Proteins and Annexins
- Kidney Stones and Urolithiasis Treatments
- Biomedical Research and Pathophysiology
- Mass Spectrometry Techniques and Applications
- Antioxidant Activity and Oxidative Stress
- Computational Drug Discovery Methods
- Endoplasmic Reticulum Stress and Disease
- Collagen: Extraction and Characterization
- Cell death mechanisms and regulation
- Microbial metabolism and enzyme function
- Protein Kinase Regulation and GTPase Signaling
Vanderbilt University Medical Center
2014-2024
Vanderbilt University
2006-2024
Matrix Research (United States)
2010
GTx (United States)
2009
University of Notre Dame
2007
University of Kansas Medical Center
1993-2002
University of Kansas
1995-2002
University Medical Center
1994
In Goodpasture's disease, circulating autoantibodies bind to the noncollagenous-1 (NC1) domain of type IV collagen in glomerular basement membrane (GBM). The specificity and molecular architecture epitopes tissue-bound are unknown. Alport's post-transplantation nephritis, which is mediated by alloantibodies against GBM, occurs after kidney transplantation some patients with syndrome. We compared conformations antibody disease nephritis intention finding clues pathogenesis anti-GBM...
Reactive carbonyl compounds are formed during autoxidation of carbohydrates and peroxidation lipids. These intermediates in the formation advanced glycation end products (AGE) lipoxidation (ALE) tissue proteins aging chronic disease. We studied reaction glyoxal (GO) glycolaldehyde (GLA) with pyridoxamine (PM), a potent post-Amadori inhibitor AGE <i>in vitro</i> development renal retinal pathology diabetic animals. PM reacted rapidly GO GLA neutral, aqueous buffer, forming Schiff base...
Diabetic nephropathy (DN) is a major life-threatening complication of diabetes. Renal lesions affect glomeruli and tubules, but the pathogenesis not completely understood. Phospholipids glycolipids are molecules that carry out multiple cell functions in health disease, their role DN unknown. We employed high spatial resolution MALDI imaging MS to determine lipid changes kidneys eNOS(-/-) db/db mice, robust model DN. Phospholipid glycolipid structures, localization patterns, relative tissue...
Hyperglycemic conditions of diabetes accelerate protein modifications by glucose leading to the accumulation advanced glycation end-products (AGEs). We have investigated conversion protein-Amadori intermediate protein-AGE and mechanism its inhibition pyridoxamine (PM), a potent AGE inhibitor that has been shown prevent diabetic complications in animal models. During incubation proteins with physiological concentrations glucose, PM prevented degradation identified as fructosyllysine (Amadori)...
Perturbation of interactions between cells and the extracellular matrix (ECM) renal glomeruli may contribute to characteristic histopathological lesions found in kidneys patients with diabetic nephropathy. However, mechanism by which conditions affect cell-ECM is unknown. Existing hypotheses suggest a role glucose direct modification ECM. Here, we have demonstrated that carbonyl compound methylglyoxal (MGO) completely inhibited endothelial cell adhesion recombinant α3 noncollagenous 1 domain...
Nonenzymatic modification of proteins in hyperglycemia is a major mechanism causing diabetic complications. These modifications can have pathogenic consequences when they target active site residues, thus affecting protein function. In the present study, we examined role glucose autoxidation functional damage using lysozyme and RGD-α3NC1 domain collagen IV as model vitro. We demonstrated that induced inhibition activity well NC1 binding to αVβ3 integrin receptor via critical arginine...
Mesangial cells and podocytes express integrins α1β1 α2β1, which are the two major collagen receptors that regulate multiple cellular functions, including extracellular matrix homeostasis. Integrin protects from glomerular injury by negatively regulating production, but role of integrin α2β1 in renal is unclear. Here, we subjected wild-type α2-null mice to with adriamycin or partial ablation. In both these models, developed significantly less proteinuria glomerulosclerosis. addition,...
In diabetes, toxic oxidative pathways are triggered by persistent hyperglycemia and contribute to diabetes complications. A major proposed pathogenic mechanism is the accumulation of protein modifications that called advanced glycation end products. However, other nonenzymatic post-translational may also damage in diabetes. We demonstrate hypohalous acid–derived renal tissues extracellular matrix (ECM) proteins significantly elevated experimental diabetic nephropathy. Moreover, ECM shows...
Establishing a non-destructive method for spatially assessing advanced glycation end-products (AGEs) is potentially useful step toward investigating the mechanistic role of AGEs in bone quality. To test hypothesis that shape amide I Raman spectroscopy (RS) analysis matrix changes upon AGE accumulation, we incubated paired cadaveric cortical ribose or glucose solutions and control 4 16 weeks, respectively, at 37°C. Acquiring 10 spectra per with 20X objective 830 nm laser, RS was sensitive to...
Isoketals and levuglandins are highly reactive γ-ketoaldehydes formed by oxygenation of arachidonic acid in settings oxidative injury cyclooxygenase activation, respectively. These compounds rapidly adduct to proteins via lysyl residues, which can alter protein structure/function. We examined whether pyridoxamine, has been shown scavenge α-ketoaldehydes carbohydrate or lipid peroxidation, could also effectively protect from the more γ-ketoaldehydes. Pyridoxamine prevented adduction ovalbumin...
Pyridoxamine (PM) is a promising drug candidate for treatment of diabetic nephropathy. The therapeutic effect PM has been demonstrated in multiple animal models diabetes and phase II clinical trials. However, the mechanism action poorly understood. One potential scavenging pathogenic reactive carbonyl species (RCS) found to be elevated diabetes. We have suggested previously that pathogenicity RCS methylglyoxal (MGO) may due modification critical arginine residues matrix proteins interference...
Matrix‐assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) is a powerful molecular mapping technology that offers unbiased visualization of the spatial arrangement biomolecules in tissue. Although there has been significant increase number applications employing this technology, extracellular matrix (ECM) received little attention, likely because ECM proteins are mostly large, insoluble and heavily cross‐linked. We have developed new sample preparation approach to...
Bromine and peroxidasin (an extracellular peroxidase) are essential for generating sulfilimine cross-links between a methionine hydroxylysine within collagen IV, basement membrane protein. The increase the structural integrity of membranes. formation depends on ability to use bromide hydrogen peroxide substrates produce hypobromous acid (HOBr). Once cross-link is created, released into space becomes available reutilization. Whether HOBr generated by used very selectively creating or whether...
Diabetic nephropathy (DN) affects both glomerular cells and the extracellular matrix (ECM), yet pathogenic mechanisms involving cell-matrix interactions are poorly understood. Glycation alters integrin-dependent cell-ECM interactions, perturbation of these results in severe renal pathology diabetic animals. Here, we investigated how chemical modifications ECM by hyperglycemia carbonyl stress, two major features milieu, affect mesangial cell functions. Incubation collagen IV with...