GAPDH inhibition mediated by thiol oxidation in human airway epithelial cells exposed to an environmental peroxide.

Intracellular redox homeostasis in the airway epithelium is closely regulated through adaptive signaling and metabolic pathways. However, inhalational exposure to xenobiotic stressors such as secondary organic aerosols (SOA) can alter intracellular redox homeostasis. Isoprene hydroxy hydroperoxide (ISOPOOH), a ubiquitous volatile organic compound derived from the atmospheric photooxidation of biogenic isoprene, is a major contributor to SOA.

Real-time redox adaptations in human airway epithelial cells exposed to isoprene hydroxy hydroperoxide.

While redox processes play a vital role in maintaining intracellular homeostasis by regulating critical signaling and metabolic pathways, supra-physiological or sustained oxidative stress can lead to adverse responses or cytotoxicity. Inhalation of ambient air pollutants such as particulate matter and secondary organic aerosols (SOA) induces oxidative stress in the respiratory tract through mechanisms that remain poorly understood. We investigated the effect of isoprene hydroxy hydroperoxide (ISOPOOH), an atmospheric oxidation product of vegetation-derived isoprene and a constituent of SOA, on intracellular redox homeostasis in cultured human airway epithelial cells (HAEC).

Fish oil blunts lung function decrements induced by acute exposure to ozone in young healthy adults: A randomized trial.

Background: Over one-third of the U.S. population is exposed to unsafe levels of ozone (O).

Live cell imaging of oxidative stress in human airway epithelial cells exposed to isoprene hydroxyhydroperoxide.

Exposure to respirable air particulate matter (PM) in ambient air is associated with morbidity and premature deaths. A major source of PM is the photooxidation of volatile plant-produced organic compounds such as isoprene. Photochemical oxidation of isoprene leads to the formation of hydroperoxides, environmental oxidants that lead to inflammatory (IL-8) and adaptive (HMOX1) gene expression in human airway epithelial cells (HAEC).

Effects of short-term increases in personal and ambient pollutant concentrations on pulmonary and cardiovascular function: A panel study analysis of the Multicenter Ozone Study in oldEr subjects (MOSES 2).

Background: The cardiovascular effects of ozone exposure are unclear. Using measurements from the 87 participants in the Multicenter Ozone Study of oldEr Subjects (MOSES), we examined whether personal and ambient pollutant exposures before the controlled exposure sessions would be associated with adverse changes in pulmonary and cardiovascular function.

Methods: We used mixed effects linear regression to evaluate associations between increased personal exposures and ambient pollutant concentrations in the 96 h before the pre-exposure visit, and 1) biomarkers measured at pre-exposure, and 2) changes in biomarkers from pre-to post-exposure.

Cardiovascular health impacts of wildfire smoke exposure.

In recent years, wildland fires have occurred more frequently and with increased intensity in many fire-prone areas. In addition to the direct life and economic losses attributable to wildfires, the emitted smoke is a major contributor to ambient air pollution, leading to significant public health impacts. Wildfire smoke is a complex mixture of particulate matter (PM), gases such as carbon monoxide, nitrogen oxide, and volatile and semi-volatile organic compounds.

Supplementation with omega-3 fatty acids potentiates oxidative stress in human airway epithelial cells exposed to ozone.

Background: Dietary intake of the omega-3 family of polyunsaturated fatty acids (ω-3 FA) is associated with anti-inflammatory effects. However, unsaturated fatty acids are susceptible to oxidation, which produces pro-inflammatory mediators. Ozone (O) is a tropospheric pollutant that reacts rapidly with unsaturated fatty acids to produce electrophilic and oxidative mediators of inflammation.

Multicenter Ozone Study in oldEr Subjects (MOSES): Part 2. Effects of Personal and Ambient Concentrations of Ozone and Other Pollutants on Cardiovascular and Pulmonary Function.

Introduction: The Multicenter Ozone Study of oldEr Subjects (MOSES) was a multi-center study evaluating whether short-term controlled exposure of older, healthy individuals to low levels of ozone (O) induced acute changes in cardiovascular biomarkers. In MOSES Part 1 (MOSES 1), controlled O exposure caused concentration-related reductions in lung function with evidence of airway inflammation and injury, but without convincing evidence of effects on cardiovascular function. However, subjects' prior exposures to indoor and outdoor air pollution in the few hours and days before each MOSES controlled O exposure may have independently affected the study biomarkers and/or modified biomarker responses to the MOSES controlled O exposures.

Do Ambient Ozone or Other Pollutants Modify Effects of Controlled Ozone Exposure on Pulmonary Function?

In a previous trial (MOSES [Multicenter Ozone Study of oldEr Subjects]), 3 hours of controlled ozone (O) exposure caused concentration-related reductions in lung function with evidence of airway inflammation and injury, but without convincing evidence of effects on cardiovascular function. However, the subjects' exposures to indoor and outdoor air pollution in the hours and days before each controlled O exposure may have modified biomarker responses to the controlled O exposures. We sought to determine whether personal measures of nitrogen dioxide (NO) and O, or ambient concentrations of O, particulate matter ≤2.

Non-redox cycling mechanisms of oxidative stress induced by PM metals.

Metallic compounds contribute to the oxidative stress of ambient particulate matter (PM) exposure. The toxicity of redox inert ions of cadmium, mercury, lead and zinc, as well as redox-active ions of vanadium and chromium is underlain by dysregulation of mitochondrial function and loss of signaling quiescence. Central to the initiation of these effects is the interaction of metal ions with cysteinyl thiols on glutathione and key regulatory proteins, which leads to impaired mitochondrial electron transport and persistent pan-activation of signal transduction pathways.

Ozone effects on blood biomarkers of systemic inflammation, oxidative stress, endothelial function, and thrombosis: The Multicenter Ozone Study in oldEr Subjects (MOSES).

The evidence that exposure to ozone air pollution causes acute cardiovascular effects is mixed. We postulated that exposure to ambient levels of ozone would increase blood markers of systemic inflammation, prothrombotic state, oxidative stress, and vascular dysfunction in healthy older subjects, and that absence of the glutathione S-transferase Mu 1 (GSTM1) gene would confer increased susceptibility. This double-blind, randomized, crossover study of 87 healthy volunteers 55-70 years of age was conducted at three sites using a common protocol.

Long chain lipid hydroperoxides increase the glutathione redox potential through glutathione peroxidase 4.

Background: Peroxidation of PUFAs by a variety of endogenous and xenobiotic electrophiles is a recognized pathophysiological process that can lead to adverse health effects. Although secondary products generated from peroxidized PUFAs have been relatively well studied, the role of primary lipid hydroperoxides in mediating early intracellular oxidative events is not well understood.

Methods: Live cell imaging was used to monitor changes in glutathione (GSH) oxidation in HAEC expressing the fluorogenic sensor roGFP during exposure to 9-hydroperoxy-10E,12Z-octadecadienoic acid (9-HpODE), a biologically important long chain lipid hydroperoxide, and its secondary product 9-hydroxy-10E,12Z-octadecadienoic acid (9-HODE).

Macrophages from the upper and lower human respiratory tract are metabolically distinct.

The function and cell surface phenotype of lung macrophages vary within the respiratory tract. Alterations in the bioenergetic profile of macrophages may also be influenced by their location within the respiratory tract. This study sought to characterize the bioenergetic profile of macrophages sampled from different locations within the respiratory tract at baseline and in response to ex vivo xenobiotic challenge.

Cardiovascular function and ozone exposure: The Multicenter Ozone Study in oldEr Subjects (MOSES).

Background: To date, there have been relatively few studies of acute cardiovascular responses to controlled ozone inhalation, although a number of observational studies have reported significant positive associations between both ambient ozone levels and acute cardiovascular events and long-term ozone exposure and cardiovascular mortality.

Objectives: We hypothesized that short-term controlled exposure to low levels of ozone in filtered air would induce autonomic imbalance, repolarization abnormalities, arrhythmia, and vascular dysfunction.

Methods: This randomized crossover study of 87 healthy volunteers 55-70 years of age was conducted at three sites using a common protocol, from June 2012 to April 2015.

Investigating mitochondrial dysfunction in human lung cells exposed to redox-active PM components.

Exposure to ambient particulate matter (PM) causes cardiopulmonary morbidity and mortality through mechanisms that involve oxidative stress. 1,2-naphthoquinone (1,2-NQ) is a ubiquitous component of PM and a potent redox-active electrophile. We previously reported that 1,2-NQ increases mitochondrial HO production through an unidentified mechanism.

Respiratory Responses to Ozone Exposure. MOSES (The Multicenter Ozone Study in Older Subjects).

Rationale: Acute respiratory effects of low-level ozone exposure are not well defined in older adults.

Objectives: MOSES (The Multicenter Ozone Study in Older Subjects), although primarily focused on acute cardiovascular effects, provided an opportunity to assess respiratory responses to low concentrations of ozone in older healthy adults.

Methods: We performed a randomized crossover, controlled exposure study of 87 healthy adults (59.

Multicenter Ozone Study in oldEr Subjects (MOSES): Part 1. Effects of Exposure to Low Concentrations of Ozone on Respiratory and Cardiovascular Outcomes.

Introduction: Exposure to air pollution is a well-established risk factor for cardiovascular morbidity and mortality. Most of the evidence supporting an association between air pollution and adverse cardiovascular effects involves exposure to particulate matter (PM). To date, little attention has been paid to acute cardiovascular responses to ozone, in part due to the notion that ozone causes primarily local effects on lung function, which are the basis for the current ozone National Ambient Air Quality Standards (NAAQS).

Effect of Obesity on Acute Ozone-Induced Changes in Airway Function, Reactivity, and Inflammation in Adult Females.

We previously observed greater ozone-induced lung function decrements in obese than non-obese women. Animal models suggest that obesity enhances ozone-induced airway reactivity and inflammation. In a controlled exposure study, we compared the acute effect of randomized 0.

Mechanisms of the acute effects of inhaled ozone in humans.

Ambient air ozone (O3) is generated photochemically from oxides of nitrogen and volatile hydrocarbons. Inhaled O3 causes remarkably reversible acute lung function changes and inflammation. Approximately 80% of inhaled O3 is deposited on the airways.

Protein Sulfenylation: A Novel Readout of Environmental Oxidant Stress.

Oxidative stress is a commonly cited mechanism of toxicity of environmental agents. Ubiquitous environmental chemicals such as the diesel exhaust component 1,2-naphthoquinone (1,2-NQ) induce oxidative stress by redox cycling, which generates hydrogen peroxide (H2O2). Cysteinyl thiolate residues on regulatory proteins are subjected to oxidative modification by H2O2 in physiological contexts and are also toxicological targets of oxidant stress induced by environmental contaminants.

Dietary Supplementation with Olive Oil or Fish Oil and Vascular Effects of Concentrated Ambient Particulate Matter Exposure in Human Volunteers.

Background: Exposure to ambient particulate matter (PM) induces endothelial dysfunction, a risk factor for cardiovascular disease. Olive oil (OO) and fish oil (FO) supplements have beneficial effects on endothelial function.

Objective: In this study we evaluated the potential efficacy of OO and FO in mitigating endothelial dysfunction and disruption of hemostasis caused by exposure to particulate matter (PM).

Role of H2O2 in the oxidative effects of zinc exposure in human airway epithelial cells.

Human exposure to particulate matter (PM) is a global environmental health concern. Zinc (Zn(2+)) is a ubiquitous respiratory toxicant that has been associated with PM health effects. However, the molecular mechanism of Zn(2+) toxicity is not fully understood.

Pulmonary responses in current smokers and ex-smokers following a two hour exposure at rest to clean air and fine ambient air particles.

Background: Increased susceptibility of smokers to ambient PM may potentially promote development of COPD and accelerate already present disease.

Objectives: To characterize the acute and subacute lung function response and inflammatory effects of controlled chamber exposure to concentrated ambient fine particles (CAFP) with MMAD  ≤  2.5 microns in ex-smokers and lifetime smokers.

Sequestration of mitochondrial iron by silica particle initiates a biological effect.

Inhalation of particulate matter has presented a challenge to human health for thousands of years. The underlying mechanism for biological effect following particle exposure is incompletely understood. We tested the postulate that particle sequestration of cell and mitochondrial iron is a pivotal event mediating oxidant generation and biological effect.