A5021583094- Protein Kinase Regulation and GTPase Signaling
- Cardiomyopathy and Myosin Studies
- Renin-Angiotensin System Studies
- Nitric Oxide and Endothelin Effects
- Advanced Proteomics Techniques and Applications
- Neurobiology and Insect Physiology Research
- Pharmacological Effects and Assays
- Retinal Development and Disorders
- Birth, Development, and Health
- Protein Tyrosine Phosphatases
- Mass Spectrometry Techniques and Applications
- Receptor Mechanisms and Signaling
- Diet and metabolism studies
- NF-κB Signaling Pathways
- Ion Transport and Channel Regulation
- Inflammasome and immune disorders
- Kruppel-like factors research
- Microbial metabolism and enzyme function
- Gastrointestinal motility and disorders
- Infectious Aortic and Vascular Conditions
- Cellular Mechanics and Interactions
- Renal Diseases and Glomerulopathies
- Angiogenesis and VEGF in Cancer
- Caveolin-1 and cellular processes
- Mitochondrial Function and Pathology
University of Calgary
2011-2024
Libin Cardiovascular Institute of Alberta
2012-2014
The mechanisms that drive leukocyte recruitment to the kidney are incompletely understood. Dipeptidase-1 (DPEP1) is a major neutrophil adhesion receptor highly expressed on proximal tubular cells and peritubular capillaries of kidney. Renal ischemia reperfusion injury (IRI) induces robust monocyte causes acute (AKI). inflammation AKI phenotype were attenuated in Dpep1-/- mice or pretreated with DPEP1 antagonists, including LSALT peptide, nonenzymatic inhibitor. deficiency inhibition...
Inflammatory bowel disease (IBD) is associated with intestinal smooth muscle dysfunction. Many contractile events are alterations in Ca<sup>2+</sup>-sensitizing pathways. The aim of the present study was to assess effect colitis on Ca<sup>2+</sup> sensitization and signaling pathways responsible for dysfunction murine experimental colitis. Colitis induced BALB/c mice by providing 5% dextran sulfate sodium (DSS) drinking water 7 days. Contractile responses colonic circular strips 118 mM...
Abstract Background Mitogen‐activated protein kinases ( MAPK s), including extracellular signal‐regulated kinase (ERK) and p38 , are known regulators of smooth muscle contractility. The contraction is mainly regulated by the phosphorylation regulatory light chains myosin II LC 20), which driven balance between chain MLCK ) phosphatase MLCP ). We hypothesized that one possible mechanism for ‐dependent modulation intestinal contractility via regulation activity. Methods Contractile responses...
Absent in melanoma-2 (AIM2) is an inflammasome-forming innate immune sensor for dsDNA but also exhibits inflammasome-independent functions such as restricting cellular proliferation. AIM2 expressed the kidney, its localization and function are not fully characterized. In normal human glomeruli, localized to podocytes. patients with glomerulonephritis, expression increased CD44+-activated parietal epithelial cells within glomerular crescents. To explore effects disease, studies Aim2-/- mice...
Abstract Background Colonic smooth muscle contractility is altered in colitis, and several protein kinase pathways can mediate colonic contraction. In the present study, we investigated whether C (PKC) also play a role hypercontractility observed during T H 2 colitis BALB/c mice. Methods Colitis was induced mice by provision of 5% dextran sodium sulfate (DSS) for 7 days. Changes were examined using dissected circular preparations from distal colon. The contribution conventional novel PKC...
The role of the smoothelin-like 1 (SMTNL1) protein in mediating vascular smooth muscle contractile responses to intraluminal pressure was examined resistance vessels. Mesenteric arterioles from wild type (WT) and SMTNL1 global knock-out (KO) mice were with myography. deletion associated enhanced myogenic tone vessels isolated male, but not female, mice. Intraluminal pressures greater than 40 mmHg generated statistically significant differences reactivity between WT KO No overt morphological...
The calponin homology-associated smooth muscle (CHASM) protein plays an important adaptive role in and skeletal contraction. CHASM is associated with increased contractility can be localized to the contractile thin filament via its binding interaction tropomyosin. We sought define structural basis for of tropomyosin as a first step understanding contribution capacity muscle. Herein, we provide structure-based model tropomyosin-binding domain using combination hydrogen/deuterium exchange mass...
Abstract The vascular smooth muscle (VSM) of resistance blood vessels is a target intrinsic autoregulatory responses to increased intraluminal pressure, the myogenic response. In brain, reactivity cerebral arteries critical homeostatic flow regulation. Here we provide first evidence link death‐associated protein kinase 3 (DAPK3) response rat and human arteries. DAPK3 Ser/Thr involved in Ca 2+ ‐sensitization mechanisms contraction. Ex vivo administration specific inhibitor (i.e., HS38) could...
The present experiments were designed to measure the effects of acute administration angiotensin (ANG) II on mean arterial pressure (MAP) and renal blood flow (RBF) in conscious, chronically instrumented lambs at two different stages postnatal maturation, determine receptors through which these ANG are elicited. Experiments consisted haemodynamic measurements for 10 s before (Control) 60 after intravenous (i.v.) one 11 doses (0-200 ng kg(-1)). Administration was associated with a...
The phosphorylation of myosin regulatory light chain (LC20) at Thr18 and Ser19 is positively correlated with tension development in smooth muscle tissue, the molar stoichiometry LC20 commonly profiled as a measure contractility. We provide details for newly applied multiple reaction monitoring (MRM)-mass spectrometry (MS) method quantification Ser19. This MRM-MS provides robust alternative to antibody-based detection systems (such Phos-Tag SDS-PAGE) phosphorylation.
We examined the role of smoothelin‐like 1 (SMTNL1) protein in mediating vascular smooth muscle contractile responses to pressure resistance vessels. Arterioles from wild type (WT) and SMTNL1 global knock‐out (KO) mice were with myography, tissues analyzed by western blotting. Mesenteric arterioles (3 rd order) Smtnl1 KO exhibited strikingly enhanced myogenic tone potential compared WT littermates. Vessels animals are more responsive acute changes, (i.e., exhibit greater response increasing...
BACKGROUND Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Ultimately, heart failure (HF) common final outcome for most patients with CVD, HF preserved ejection fraction (HFpEF) has gained increasing prevalence. Clinical evidence associates HFpEF microvascular dysfunction endothelial inflammation, which in turn drive pathologic cardiac remodeling. No therapeutics are available improving outcomes patients; thus, further research required to better...
This study was designed to investigate the role of endogenously produced angiotensin II (ANG II) in modulating systemic and renal hemodynamics during postnatal maturation as well receptors through which it exerts these effects. Experiments were carried out conscious, chronically instrumented lambs aged ~one-week (age 8±2 days, n=14) ~six weeks 41±3 n=23). At least four days after surgery under halothane anesthesia for placement vessel catheters a flow transducer around left artery...
ABSTRACT The vascular smooth muscle (VSM) of resistance blood vessels displays intrinsic autoregulatory responses to increased intraluminal pressure, the myogenic response. In brain, cerebral arterioles are critical homeostatic flow regulation. Here we provide first evidence link death-associated protein kinase 3 (DAPK3) response rat and human arterioles. DAPK3 is a Ser/Thr involved in Ca2+− sensitization mechanisms VSM contraction. Ex vivo administration specific inhibitor (i.e., HS38)...