A5101917494- Mitochondrial Function and Pathology
- Pulmonary Hypertension Research and Treatments
- ATP Synthase and ATPases Research
- Phenothiazines and Benzothiazines Synthesis and Activities
- Nitric Oxide and Endothelin Effects
- RNA modifications and cancer
- Ubiquitin and proteasome pathways
- Essential Oils and Antimicrobial Activity
- Metabolism and Genetic Disorders
- Phytochemistry and Bioactivity Studies
- Chemical synthesis and alkaloids
- MicroRNA in disease regulation
- Cardiomyopathy and Myosin Studies
- Cardiovascular Function and Risk Factors
- Cholinesterase and Neurodegenerative Diseases
- Calcium signaling and nucleotide metabolism
- COVID-19 Clinical Research Studies
- Takotsubo Cardiomyopathy and Associated Phenomena
- Nicotinic Acetylcholine Receptors Study
- Cancer, Hypoxia, and Metabolism
- Cellular transport and secretion
- Quinazolinone synthesis and applications
- Phosphodiesterase function and regulation
- Antimicrobial Peptides and Activities
- Atomic and Subatomic Physics Research
Queen's University
2015-2024
Institute of Medical Sciences
1992-2015
National Institute on Aging
2015
National Institutes of Health
2015
Jadavpur University
2004-2014
Rationale: Pulmonary arterial hypertension (PAH) often results in death from right ventricular failure (RVF). NLRP3 (nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3)-macrophage activation may promote RVF PAH. Objectives: Evaluating the contribution of inflammasome RV macrophages to PAH RVF. Methods: Rats with decompensated hypertrophy (monocrotaline [MCT] and Sugen-5416 hypoxia [SuHx]) were compared compensated rats (pulmonary artery banding)....
Rationale: Pulmonary arterial hypertension (PAH) is an obstructive vasculopathy characterized by excessive pulmonary artery smooth muscle cell (PASMC) proliferation, migration, and apoptosis resistance. This cancer-like phenotype promoted increased cytosolic calcium ([Ca2+]cyto), aerobic glycolysis, mitochondrial fission.Objectives: To determine how changes in uniporter (MCU) complex (MCUC) function influence dynamics contribute to PAH’s phenotype.Methods: PASMCs were isolated from patients...
Mitotic fission is increased in pulmonary arterial hypertension (PAH), a hyperproliferative, apoptosis-resistant disease. The mediator dynamin-related protein 1 (Drp1) must complex with adaptor proteins to cause fission. Drp1-induced has been therapeutically targeted experimental PAH. Here, we examine the role of 2 recently discovered, poorly understood Drp1 adapter proteins, mitochondrial dynamics 49 and 51 kDa (MiD49 MiD51), normal vascular cells explore their dysregulation PAH.Immunoblots...
Rationale: Right ventricular (RV) fibrosis in pulmonary arterial hypertension contributes to RV failure. While reflects changes the function of resident fibroblasts (RVfib), these cells are understudied. Objective: Examine role mitochondrial metabolism RVfib human and experimental hypertension. Methods Results: Male Sprague-Dawley rats received monocrotaline (MCT; 60 mg/kg) or saline. Drinking water containing no supplement PDK (pyruvate dehydrogenase kinase) inhibitor dichloroacetate was...
Abstract Mitochondrial fission is important in physiological processes, including coordination of mitochondrial and nuclear division during mitosis, pathologic such as the production reactive oxygen species (ROS) cardiac ischemia‐reperfusion injury (IR). mainly mediated by dynamin‐related protein 1 (Drp1), a large GTPase. The GTPase activity Drp1 essential for its fissogenic activity. Therefore, we aimed to identify inhibitors evaluate their anti‐neoplastic cardioprotective properties five...
It has been reported that Mitofusin2 (Mfn2) inhibits cell proliferation when overexpressed. We wanted to study the role of endogenous Mfn2 in proliferation, along with structural features influence its mitochondrial localization and control proliferation. Mfn2-knockdown clones a B-cell lymphoma line BJAB exhibited an increased rate A 2-fold increase was also observed Mfn2-knockout mouse embryonic fibroblast (MEF) cells as compared wild-type cells, proliferative advantage knockout MEF blocked...
Right ventricular (RV) fibrosis contributes to RV failure in pulmonary arterial hypertension (PAH). The mechanisms underlying PAH and the role of fibroblasts (RVfib) are unknown. Activation mitochondrial fission mediator dynamin-related protein 1 (Drp1) dysfunction myocytes through interaction with its binding partner, (Fis1). However, RVfib is
Impaired mitochondrial fusion, due in part to decreased mitofusin 2 (Mfn2) expression, contributes unrestricted cell proliferation and apoptosis-resistance hyperproliferative diseases like pulmonary arterial hypertension (PAH) non-small lung cancer (NSCLC).We hypothesized that Mfn2 levels are reduced increased proteasomal degradation of triggered by its phosphorylation at serine 442 (S442) investigated the potential kinase mediators.Mfn2 expression was S442 artery smooth muscle cells from...
Introduction: Group 2 pulmonary hypertension (PH), defined as a mean arterial pressure ≥25 mmHg with elevated capillary wedge >15 mmHg, has no approved therapy and patients often die from right ventricular failure (RVF). Alterations in mitochondrial metabolism, notably impaired glucose oxidation, increased fission, contribute to ventricle (RV) dysfunction PH. We hypothesized that the impairment of RV left (LV) function group PH results part proglycolytic isoform switch pyruvate kinase muscle...
Drp1 (dynamin-related protein 1), a large GTPase, mediates the increased mitochondrial fission, which contributes to hyperproliferation of pulmonary artery smooth muscle cells in arterial hypertension (PAH). We developed potent GTPase inhibitor, Drpitor1a, but its specificity, pharmacokinetics, and efficacy PAH are unknown.
Excessive proliferation and apoptosis-resistance are hallmarks of cancer. Increased dynamin-related protein 1 (Drp1)-mediated mitochondrial fission is one the mediators this phenotype. Mitochondrial that accompanies nuclear division called mitotic occurs when activated Drp1 binds partner proteins on outer membrane. We examine role Drp1-binding partners, dynamics 49 51 kDa (MiD49 MiD51), as drivers cell in non-small lung cancer (NSCLC) invasive breast carcinoma (IBC). also evaluate whether...
Mitofusin 2 (Mfn2), a mitochondrial protein, was shown to have antiproliferative properties when overexpressed. In this article, we show that activation of resting human peripheral blood T cells caused downregulation Mfn2 levels. This blocked by different inhibitors (mTOR inhibitor rapamycin, PI3K LY294002, and Akt A443654), producing were arrested in the G0/G1 stage cell cycle. Furthermore, activation-induced preceded entry into cycle, suggesting is prerequisite for activated Accordingly,...
Group 2 pulmonary hypertension (PH) has no approved PH-targeted therapy. Metabolic remodelling, specifically a biventricular increase in pyruvate kinase muscle (PKM) isozyme to 1 ratio, occurs rats with group PH induced by supra-coronary aortic banding (SAB). We hypothesize that increased PKM2/PKM1 is maladaptive and inhibiting PKM2 would improve right ventricular (RV) function.Male, Sprague-Dawley SAB were confirmed have echocardiography then randomized treatment inhibitor (intraperitoneal...