use-electron-paramagnetic-resonance-biological-samples-at-ambient

Use of Electron Paramagnetic Resonance in Biological Samples at Ambient Temperature and 77 K

The accurate and specific detection of reactive oxygen species (ROS) in different cellular and tissue compartments is essential to the study of ...

University of Colorado Anschutz Medical Campus

When evaluating the role of redox-regulating signaling in pulmonary vascular diseases, it is intriguing to consider the modulation of key antioxidant enzymes like superoxide dismutase (SOD) because SOD isoforms are regulated by redox reactions, and, in turn, modulate downstream redox sensitive processes. The emerging field of redox biology is built upon understanding the regulation and consequences of tightly controlled and specific reduction-oxidation reactions that are critical for diverse cellular processes including cell signaling. Of relevance, both the site of production of specific reactive oxygen and nitrogen species and the site of the antioxidant defenses are highly compartmentalized within the cell. For example, superoxide is generated during oxidative phosphorylation in the mitochondria as well as by a number of enzymatic sources within the cytosol and at the cell membrane. In the pulmonary circulation, these sources include the mitochondrial electron transport chain, NADPH oxidases (NOX1-4, Duox1,2), nitric oxide synthases, and xanthine oxidase; this important topic has been thoroughly reviewed recently [1]. In parallel with these different cellular sites of superoxide production, the three SOD isoforms are also specifically localized to the cytosol (SOD1), mitochondria (SOD2) or extracellular compartment (SOD3). This chapter focuses on the role of redox mechanisms regulating SOD2 and SOD3, with an emphasis on these processes in the setting of pulmonary hypertension.

Redox Regulation of the Superoxide Dismutases SOD3 and SOD2 in the Pulmonary Circulation.

A naturally occurring single nucleotide polymorphism (SNP), (RG), in extracellular superoxide dismutase (SOD3), decreases SOD3 matrix binding affinity. Humans and mature mice expressing the RG SNP exhibit increased cardiovascular disease but decreased lung disease. The impact of this SNP on the neonatal lung at baseline or with injury is unknown.

Redistribution of Extracellular Superoxide Dismutase Causes Neonatal Pulmonary Vascular Remodeling and PH but Protects Against Experimental Bronchopulmonary Dysplasia.

Pulmonary hypertension (PH) is a progressive disease characterized by pulmonary vascular remodeling and lung vasculopathy. The disease displays progressive dyspnea, pulmonary artery uncoupling, and right ventricular (RV) dysfunction. The molecular events that promote the development of pulmonary hypertension are complex and incompletely understood. Metabolic impairment has been proposed to contribute to the pathophysiology of PH with evidence for mitochondrial dysfunction involving the electron transport chain proteins, antioxidant enzymes, apoptosis regulators and mitochondrial quality control. It is vital to characterize the mechanisms by which mitochondrial dysfunction contribute to PH pathogenesis. This review focus on the currently available publications that supports mitochondrial mechanisms in PH pathophysiology. Further studies of these metabolic mitochondrial alterations in PH could be viable targets of therapeutic intervention.

Eva Nozik-Grayck

Cardiovascular Pulmonary Research Laboratories and Pediatric Critical Care Medicine,
Department of Pediatrics,
Cardiovascular Pulmonary Research Laboratories and Pediatric Critical Care Medicine, Department of Pediatrics

University of Colorado Anschutz Medical Campus

Use of Electron Paramagnetic Resonance in Biological Samples at Ambient Temperature and 77 K

Eva Nozik-Grayck

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Cardiovascular Pulmonary Research Laboratories and Pediatric Critical Care Medicine,Department of Pediatrics,Cardiovascular Pulmonary Research Laboratories and Pediatric Critical Care Medicine, Department of Pediatrics

University of Colorado Anschutz Medical Campus

Use of Electron Paramagnetic Resonance in Biological Samples at Ambient Temperature and 77 K

Cardiovascular Pulmonary Research Laboratories and Pediatric Critical Care Medicine,
Department of Pediatrics,
Cardiovascular Pulmonary Research Laboratories and Pediatric Critical Care Medicine, Department of Pediatrics