A5027228738- Glutathione Transferases and Polymorphisms
- Sulfur Compounds in Biology
- Redox biology and oxidative stress
- Neonatal Respiratory Health Research
- Asthma and respiratory diseases
- Ion Channels and Receptors
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Genomics, phytochemicals, and oxidative stress
- Pain Mechanisms and Treatments
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Pulmonary Hypertension Research and Treatments
- Cancer, Hypoxia, and Metabolism
- Cancer Research and Treatments
- Advanced Glycation End Products research
- Immune cells in cancer
- Neuropeptides and Animal Physiology
- Microbial metabolism and enzyme function
- Amino Acid Enzymes and Metabolism
- Neurobiology and Insect Physiology Research
- Eosinophilic Esophagitis
- Heat shock proteins research
- Exercise and Physiological Responses
- Ubiquitin and proteasome pathways
- Mast cells and histamine
- Biochemical and Structural Characterization
University of Vermont
2017-2025
Emory University Hospital
2021
University of Calgary
2014-2019
Alberta Children's Hospital
2019
Alberta Children's Hospital Research Institute
2018
Glutathione (GSH) is a critical component of the cellular redox system that combats oxidative stress. The glutamate-cystine antiporter, x
Glutathione is a major redox buffer, reaching millimolar concentrations within cells and high micromolar in airways. While glutathione has been traditionally known as an antioxidant defense mechanism that protects the lung tissue from oxidative stress, more recently become recognized for its ability to covalently conjugated reactive cysteines proteins, modification S-glutathionylation (or S-glutathiolation or protein mixed disulfide). potential change structure function of target protein,...
Abstract Asthma is a chronic disorder characterized by inflammation, mucus metaplasia, airway remodeling, and hyperresponsiveness. We recently showed that IL-1–induced glycolytic reprogramming contributes to allergic disease using murine house dust mite model. Moreover, levels of pyruvate kinase M2 (PKM2) were increased in this model as well nasal epithelial cells from asthmatics compared with healthy controls. Although the tetramer form PKM2 converts phosphoenolpyruvate pyruvate, dimeric...
Pain and inflammation are inherently linked responses to injury, infection, or chronic diseases. Given that acute in humans mice enhances the analgesic properties of opioids, there is much interest determining inflammatory transducers prime opioid receptor signaling primary afferent nociceptors. Here, we found activation transient potential vanilloid type 1 (TRPV1) channel stimulated a mitogen-activated protein kinase (MAPK) pathway was accompanied by shuttling scaffold β-arrestin2 nucleus....
Interleukin-1-dependent increases in glycolysis promote allergic airways disease mice and disruption of pyruvate kinase M2 (PKM2) activity is critical herein. Glutathione-S-transferase P (GSTP) has been implicated asthma pathogenesis regulates the oxidation state proteins via S-glutathionylation. We addressed whether GSTP-dependent S-glutathionylation promotes by promoting glycolytic reprogramming it involves PKM2.
Abstract The small thiol antioxidant glutathione (GSH) is critical in maintaining redox homeostasis that essential combating oxidative stress. We and others have reported increases of GSH KRAS-mutant lung adenocarcinoma (LUAD). However, little known about GSH-dependent protein oxidation (S-glutathionylation- PSSG) LUAD development progression. recently discovered glutaredoxin (GLRX), the enzyme reverses PSSG, decreased human LUAD, KrasG12D-induced tumorigenesis enhanced mice lacking Glrx. To...
Background Specialized cellular defense mechanisms prevent damage from chemical, biological, and physical hazards. The heat shock proteins have been recognized as key chaperones that maintain cell survival against a variety of exogenous endogenous stress signals including noxious temperature. However, the role in nociception remains poorly understood. We carried out an expression analysis constitutively expressed 70 kDa heat-shock cognate protein, member stress-induced HSP70 family lumbar...
Glycolysis is a well-known process by which metabolically active cells, such as tumor or immune cells meet their high metabolic demands. Previously, our laboratory has demonstrated that in airway epithelial the pleiotropic cytokine, interleukin-1 beta (IL1B) induces glycolysis and this contributes to allergic inflammation remodeling. Activation of known increase NADPH reducing equivalents generated from pentose phosphate pathway, linking reprogramming with redox homeostasis. In addition,...
Changes in the oxidative (redox) environment accompany idiopathic pulmonary fibrosis (IPF). S-glutathionylation of reactive protein cysteines is a post-translational event that transduces oxidant signals into biological responses. We recently demonstrated increases promote fibrosis, which was mitigated by deglutathionylating enzyme glutaredoxin (GLRX). However, targets fibrogenesis remain unknown. In present study we addressed whether extracellular matrix target for S-glutathionylation....
Abstract As the emergence of bacterial resistance is outpacing development new antibiotics, we must find cost-effective and innovative approaches to discover antibacterial therapeutics. Antimicrobial peptides (AMPs) represent one promising solution fill this void, since they generally undergo faster development, display rapid onsets killing, most importantly, show lower risks induced resistance. Despite prior success in AMP design with physics- and/or knowledge-based approaches, an efficient...
Obesity is a risk factor for the development of asthma and represents difficult-to-treat disease phenotype. Aerobic glycolysis emerging as key feature asthma, changes in glucose metabolism are linked to leukocyte activation adaptation oxidative stress. Dysregulation PKM2 (pyruvate kinase M2), enzyme that catalyzes last step glycolysis, contributes house dust mite (HDM)–induced airway inflammation remodeling lean mice. It remains unclear whether glycolytic reprogramming dysregulation also...
S-glutathionylation of reactive protein cysteines is a post-translational event that plays critical role in transducing signals from oxidants into biological responses. can be reversed by the deglutathionylating enzyme glutaredoxin (GLRX). We have previously demonstrated ablation Glrx sensitizes mice to development parenchymal lung fibrosis(1). It remains unclear whether GLRX also controls airway fibrosis, clinical feature relevant asthma and chronic obstructive pulmonary disease, biology...
Abstract Acute inflammation in humans or mice enhances the analgesic properties of opioids. However, inflammatory transducers that prime opioid receptor signaling nociceptors are unknown. We found TRPV1 −/− insensitive to peripheral analgesia an pain model. report channel activation drives a MAPK pathway accompanied by shuttling β-arrestin2 nucleus. This turn prevents: β-arrestin2-receptor recruitment, subsequent internalization agonist-bound mu (MOR), and suppression DAMGO-induced...