A5042890673- Mitochondrial Function and Pathology
- Nitric Oxide and Endothelin Effects
- Cancer, Hypoxia, and Metabolism
- High Altitude and Hypoxia
- Pulmonary Hypertension Research and Treatments
- Cardiac Ischemia and Reperfusion
- Neuroscience of respiration and sleep
- Neonatal Respiratory Health Research
- Eicosanoids and Hypertension Pharmacology
- Medical Imaging and Pathology Studies
- Redox biology and oxidative stress
- Cardiovascular Function and Risk Factors
- Anesthesia and Neurotoxicity Research
- ATP Synthase and ATPases Research
- Adipose Tissue and Metabolism
- Traumatic Brain Injury and Neurovascular Disturbances
- Congenital Heart Disease Studies
- Heat shock proteins research
- Heme Oxygenase-1 and Carbon Monoxide
- Congenital heart defects research
- Pancreatic function and diabetes
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Hemodynamic Monitoring and Therapy
- Hemoglobinopathies and Related Disorders
- Cardiac Fibrosis and Remodeling
Northwestern University
2007-2024
Pediatrics and Genetics
2020
Lurie Children's Hospital
2019
Northwestern Medicine
2018
University of Chicago
2001-2009
Albany Medical Center Hospital
1996-2000
AMP-activated protein kinase (AMPK) is an energy sensor activated by increases in [AMP] or oxidant stress (reactive oxygen species [ROS]). Hypoxia cellular ROS signaling, but the pathways underlying subsequent AMPK activation are not known. We tested hypothesis that hypoxia activates ROS-mediated opening of calcium release-activated (CRAC) channels. (1.5% O(2)) augments as detected redox-sensitive green fluorescent (roGFP) does increase [AMP]/[ATP] ratio. Increases intracellular during were...
Rationale : Recent studies have implicated mitochondrial reactive oxygen species (ROS) in regulating hypoxic pulmonary vasoconstriction (HPV), but controversy exists regarding whether hypoxia increases or decreases ROS generation. Objective This study tested the hypothesis that induces redox changes differ among subcellular compartments (PASMCs) and systemic (SASMCs) smooth muscle cells. Methods Results We used a novel, redox-sensitive, ratiometric fluorescent protein sensor (RoGFP) to...
Chronic hypoxia induces pulmonary vascular remodeling, hypertension, and right ventricular hypertrophy. At present, little is known about mechanisms driving these responses. Hypoxia-inducible factor-1α (HIF-1α) a master regulator of transcription in hypoxic cells, up-regulating genes involved energy metabolism, proliferation, extracellular matrix reorganization. Systemic loss single HIF-1α allele has been shown to attenuate but the cells contributing this response have not identified.We...
Abstract —We tested whether mitochondria function as the O 2 sensor underlying hypoxic pulmonary vasoconstriction (HPV). In buffer-perfused rat lungs, rotenone, myxothiazol, and diphenyleneiodonium, which inhibit in proximal region of electron transport chain (ETC), abolished HPV without attenuating response to U46619. Cyanide antimycin A transfer distal ETC, but they did not abolish HPV. Cultured artery (PA) myocytes contract hypoxia or The was while U46619 maintained mutant (ρ 0 ) PA...
We hypothesized that mitochondria function as the O 2 sensors underlying hypoxic pulmonary vasoconstriction by releasing reactive oxygen species (ROS) from complex III of electron transport chain (ETC). have previously found antioxidants or inhibition proximal region ETC attenuates in rat lungs and blocks hypoxia-induced contraction isolated arterial (PA) myocytes. To determine whether increases mitochondrial ROS act to trigger calcium increases, we measured changes cytosolic ([Ca 2+ ] i )...
Mitochondria have been implicated as a potential site of O(2) sensing underlying hypoxic pulmonary vasoconstriction (HPV), but 2 disparate models proposed to explain their reaction hypoxia. One model proposes that hypoxia-induced increases in mitochondrial reactive oxygen species (ROS) generation activate HPV through an oxidant-signaling pathway, whereas the other is result decreased oxidant signaling. In attempt resolve this debate, we use novel, ratiometric, redox-sensitive fluorescence...
The role of reactive oxygen species (ROS) signaling in the O(2) sensing mechanism underlying acute hypoxic pulmonary vasoconstriction (HPV) has been controversial. Although mitochondria are important sources ROS, studies using chemical inhibitors have yielded conflicting results, whereas cellular models genetic suppression precluded vivo confirmation. Hence, animal required to test mechanistic hypotheses.We tested whether mitochondrial Complex III is for ROS and responses hypoxia arteries...
Ischemia-reperfusion injury induces oxidant stress, and the burst of reactive oxygen species (ROS) production after reperfusion ischemic myocardium is sufficient to induce cell death. Mitochondrial may begin during ischemia prior because reducing equivalents accumulate promote superoxide production. We utilized a ratiometric redox-sensitive protein sensor (heat shock 33 fluorescence resonance energy transfer (HSP-FRET)) assess stress in cardiomyocytes simulated ischemia. HSP-FRET consists...
Precapillary arteries constrict during alveolar hypoxia in a response known as hypoxic pulmonary vasoconstriction (HPV). The mechanism by which arterial smooth muscle cells (PASMCs) detect decrease Po(2) and trigger contraction is not fully understood. Previous studies cultured PASMCs show that induces an increase reactive oxygen species (ROS) production, but these results may reflect responses of their native tissue environment. We therefore assessed hypoxia-induced changes cytosolic ROS...
Phase I of the hypoxic pulmonary vasoconstriction (HPV) response begins upon transition to hypoxia and involves an increase in cytosolic calcium ([Ca(2+)](i)). II develops during prolonged increases constriction without further [Ca(2+)](i), suggesting Ca(2+) sensitivity. Prolonged activates RhoA kinase, which may sensitivity, but mechanism is unknown. We previously found that reactive oxygen species (ROS) trigger I. therefore asked whether ROS generation PA smooth muscle cells (PASMCs)...
The ability to adapt acute and chronic hypoxia is critical for cellular survival. Two established functional responses include the regulation of gene transcription by HIF (hypoxia-inducible factor), constriction pulmonary arteries in response alveolar hypoxia. mechanism O2 sensing these not established, but some studies implicate hypoxia-induced mitochondrial ROS (reactive oxygen species) signalling. To further test this hypothesis, we expressed PRDX5 (peroxiredoxin-5), a H2O2 scavenger, IMS...
Pulmonary hypertension (PH) and right ventricular (RV) hypertrophy frequently develop in patients with hypoxic lung disease. Chronic alveolar hypoxia (CH) promotes sustained pulmonary vasoconstriction artery (PA) remodeling by acting on cells, resulting the development of PH. RV develops response to PH, but coronary arterial hypoxemia CH may influence that activating HIF-1α (hypoxia-inducible factor 1α) and/or HIF-2α cardiomyocytes. Indeed, other studies show attenuation PH fails prevent...
Newborn mammalian cardiomyocytes quickly transition from a fetal to an adult phenotype that utilizes mitochondrial oxidative phosphorylation but loses mitotic capacity. We tested whether forced reversal of back glycolytic would restore proliferative deleted Uqcrfs1 (mitochondrial Rieske Iron-Sulfur protein, RISP) in hearts mice. As RISP protein decreased, heart function declined, and glucose utilization increased. Simultaneously, they underwent hyperplastic remodeling during which...
Doxorubicin (Dox) is one of the most widely used and successful chemotherapeutic antitumor drugs. Its clinical application highly limited due to its cumulative dose-related cardiotoxicity. Proposed mechanisms include generation reactive oxygen species (ROS)-mediated oxidative stress. Therefore, reducing stress should be protective against Dox-induced To determine whether antioxidant, grape seed proanthocyanidin extract (GSPE) attenuates ROS protects cardiomyocytes from oxidant injury,...
Activated polymorphonuclear leukocytes generate a cascade of reduced oxygen metabolites. In addition to their antimicrobial role, hydrogen peroxide (H2O2) and hypochlorous acid (HOCl) function as inflammatory mediators increase the protein permeability vascular endothelium. The objectives present study were compare effects H2O2 HOCl with respect relative potencies time course magnitude changes in cell shape endothelial monolayers derived from bovine pulmonary artery, determine if produced by...
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