Cardiac and pulmonary oxidative stress in rats exposed to realistic emissions of source aerosols.

In vivo chemiluminescence (CL) is a measure of reactive oxygen species in tissues. CL was used to assess pulmonary and cardiac responses to inhaled aerosols derived from aged emissions of three coal-fired power plants in the USA. Sprague-Dawley rats were exposed to either filtered air or: (1) primary emissions (P); (2) ozone oxidized emissions (PO); (3) oxidized emissions + secondary organic aerosol (SOA) (POS); (4) neutralized oxidized emissions + SOA (PONS); and (5) control scenarios: oxidized emissions + SOA in the absence of primary particles (OS), oxidized emissions alone (O), and SOA alone (S).

The toxicological evaluation of realistic emissions of source aerosols study: statistical methods.

The Toxicological Evaluation of Realistic Emissions of Source Aerosols (TERESA) study involved withdrawal, aging, and atmospheric transformation of emissions of three coal-fired power plants. Toxicological evaluations were carried out in rats exposed to different emission scenarios with extensive exposure characterization. Data generated had multiple levels of resolution: exposure, scenario, and constituent chemical composition.

Cardiac oxidative stress and dysfunction by fine concentrated ambient particles (CAPs) are mediated by angiotensin-II.

Inhalation exposure to fine concentrated ambient particles (CAPs) increases cardiac oxidants by mechanisms involving modulation of the sympathovagal tone on the heart. Angiotensin-II is a potent vasoconstrictor and a sympatho-excitatory peptide involved in the regulation of blood pressure. We hypothesized that increases in angiotensin-II after fine particulate matter (PM) exposure could be involved in the development of cardiac oxidative stress.

Pulmonary inflammation by ambient air particles is mediated by superoxide anion.

Lung inflammation is a key response to increased levels of particulate air pollution (PM); however, the cellular mechanisms leading to this response remain poorly understood. We have previously shown that oxidants are critical mediators of the inflammatory response elicited by inhalation of ambient air particles. Here we tested the possible role of a specific oxidant, superoxide anion, by using the membrane-permeable analog of superoxide dismutase, Mn(III) tetrakis(4-benzoic acid)porphyrin chloride (MnTBAP).

Cardiac oxidative stress and electrophysiological changes in rats exposed to concentrated ambient particles are mediated by TRP-dependent pulmonary reflexes.

Previous studies suggest that, through the stimulation of pulmonary nervous endings, ambient particles modulate the autonomic tone on the heart leading to cardiac oxidant stress and dysfunction. In this paper we investigated the effect of blockade of vanilloid receptor 1 (Transient Receptor Potential Vanilloid Receptor 1 [TRPV1]) on concentrated ambient particles (CAPs)-induced cardiac oxidative stress and dysfunction in a rat model of inhalation exposure. Capsazepine (CPZ), a selective antagonist of TRPV1, was given ip or as an aerosol immediately before exposure to CAPs.

Ambient particulate matter exhibits direct inhibitory effects on oxidative stress enzymes.

A primary mechanistic hypothesis by which ambient air particles have a significant negative impact on human health is via the induction of pulmonary inflammatory responses mediated through the generation of reactive oxygen species (ROS). Development of a biosensor for the assessment of particulate ROS activity would be a significant advance in air pollution monitoring. The objective of this study was to evaluate whether air particulates interact directly with protective enzymes involved in oxidative stress responses.

PM-induced cardiac oxidative stress and dysfunction are mediated by autonomic stimulation.

Epidemiological studies show that increases in particulate air pollution (PM) are associated with increases in cardiopulmonary morbidity and mortality. However, the mechanism(s) underlying the cardiac effects of PM remain unknown. We used pharmacological strategies to determine whether oxidants are implicated in PM-dependent cardiac dysfunction and whether PM-induced increase in autonomic stimulation on the heart mediates cardiac oxidative stress and toxicity.

H2O2-induced proliferation of primary alveolar epithelial cells is mediated by MAP kinases.

Exposure to supraphysiological oxygen concentrations during ventilatory oxygen therapy often causes tissue damage. Alveolar type II (AT II) cells are a major target for oxidant injury, and their ability to proliferate plays a critical role during the repair phase following injury. We hypothesized that reactive oxygen species (ROS), which are produced during hyperoxia, not only cause cellular damage, but may also play a role in the repair process by promoting AT II cell proliferation.

Lysosomal and mitochondrial pathways in H2O2-induced apoptosis of alveolar type II cells.

Increasing evidence suggests a role for apoptosis in the maintenance of the alveolar epithelium under normal and pathological conditions. However, the signaling pathways modulating alveolar type II (AT II) cell apoptosis remain poorly defined. Here we investigated the role of lysosomes as modulators of oxidant-mediated AT II cell apoptosis using an in vitro model of H(2)O(2)-stress.

Mitogen-activated protein kinases modulate H(2)O(2)-induced apoptosis in primary rat alveolar epithelial cells.

Increasing evidence suggests a role for apoptosis in the maintenance of the alveolar epithelium under normal and pathological conditions. However, the signaling pathways modulating alveolar type II (ATII) cell apoptosis remain poorly defined. Here we investigated the role of MAPKs as modulators of oxidant-mediated ATII cell apoptosis using in vitro models of H(2)O(2)-stress.

N-acetylcysteine prevents lung inflammation after short-term inhalation exposure to concentrated ambient particles.

Lung inflammation is a key response to increased levels of particulate air pollution (PM); however, the cellular mechanisms leading to this response are poorly understood. To determine whether oxidants are implicated in PM-dependent lung inflammation, we tested the ability of N-acetylcysteine (NAC) to prevent lung inflammation in a rat model of short-term exposure to concentrated ambient particles (CAPs). Adult Sprague-Dawley rats were exposed to either CAPs aerosols (CAPs mass concentration 1060 +/- 300 microg/m(3)) or filtered air (Sham controls) for 5 h.

Oxidant mechanisms in response to ambient air particles.

The toxic effects of air pollution are widely documented. In recent years, however, there has been an increasing interest in the study of the health effects of particulate matter (PM), a previously unexplored constituent of urban air pollution. Exposure to increased levels of PM of respirable size is strongly and consistently associated with increased cardiopulmonary morbidity and mortality.

TOR kinase and Ran are downstream from PI3K/Akt in H2O2-induced mitosis.

Hydrogen peroxide (H2O2) activates signaling cascades essential for cell proliferation via phosphatidylinositol-3-kinase (PI3K) and Akt. Here we show that induction of mitogenic signaling by H2O2 activates sequentially PI3K, Akt, mammalian target of rapamycin (mTOR), and Ran protein. Akt activation is followed by signaling through the mTOR kinase and upregulation of Ran in primary type II pneumocytes, a cell type implicated in the development of lung adenocarcinoma.

Reactive oxygen species in pulmonary inflammation by ambient particulates.

Exposure to ambient air pollution particles (PM) has been associated with increased cardiopulmonary morbidity and mortality, particularly in individuals with pre-existing disease. Exacerbation of pulmonary inflammation in susceptible people (e.g.

Signaling through Cdk2, importin-alpha and NuMA is required for H2O2-induced mitosis in primary type II pneumocytes.

Proliferation of alveolar type II pneumocytes, the multipotent stem cells of the alveoli, has been implicated in the development of lung adenocarcinoma. Hydrogen peroxide (H(2)O(2)), a potent promoter of signaling cascades, can mediate the transmission of many intracellular signals including those involved in cell proliferation. In this study using rat primary type II pneumocytes, we demonstrate that H(2)O(2) significantly increases mitosis through a pathway that includes cyclin-dependent kinase 2 (Cdk2); importin-alpha, a nuclear trafficking regulator; and nuclear mitotic apparatus protein (NuMA), an essential component in mitotic spindle pole formation.

Rapid increases in the steady-state concentration of reactive oxygen species in the lungs and heart after particulate air pollution inhalation.

In vitro studies suggest that reactive oxygen species contribute to the cardiopulmonary toxicity of particulate air pollution. To evaluate the ability of particulate air pollution to promote oxidative stress and tissue damage in vivo, we studied a rat model of short-term exposure to concentrated ambient particles (CAPs). We exposed adult Sprague-Dawley rats to either CAPs aerosols (group 1; average CAPs mass concentration, 300 +/- 60 micro g/m3) or filtered air (sham controls) for periods of 1-5 hr.