Monthly Archive for September 2009

Mitochondrial Dysfunction Increases Allergic Airway Inflammation

Asthma from environmental PollutionThe prevalence of allergies and asthma among the world’s population has been steadily increasing due to environmental factors. 

 It has been described that exposure to ozone, diesel exhaust particles, or tobacco smoke exacerbates allergic inflammation in the lungs. These environmental oxidants increase the levels of cellular reactive oxygen species (ROS) and induce mitochondrial dysfunction in the airway epithelium. 

In this study, we investigated the involvement of preexisting mitochondrial dysfunction in the exacerbation of allergic airway inflammation. After cellular oxidative insult induced by ragweed pollen extract (RWE) exposure, we have identified nine oxidatively damaged mitochondrial respiratory chain-complex and associated proteins. Out of these, the ubiquinol-cytochrome c reductase core II protein (UQCRC2) was found to be implicated in mitochondrial ROS generation from respiratory complex III. Mitochondrial dysfunction induced by deficiency of UQCRC2 in airway epithelium of sensitized BALB/c mice prior the RWE challenge increased the Ag-induced accumulation of eosinophils, mucin levels in the airways, and bronchial hyperresponsiveness. Deficiency of UQCRC1, another oxidative damage-sensitive complex III protein, did not significantly alter cellular ROS levels or the intensity of RWE-induced airway inflammation. 

These observations suggest that preexisting mitochondrial dysfunction induced by oxidant environmental pollutants is responsible for the severe symptoms in allergic airway inflammation. These data also imply that mitochondrial defects could be risk factors and may be responsible for severe allergic disorders in atopic individuals. 

Reference:  Aguilera-Aguirre L, Bacsi A, Saavedra-Molina A, Kurosky A, Sur S, Boldogh I., Mitochondrial Dysfunction Increases Allergic Airway Inflammation, J Immunol. 2009 Sep 28.

Air Pollutants From Abroad a Growing Concern, Says New Report

Pollution respects no borders it travels across borders

Plumes of harmful air pollutants can be transported across oceans and continents — from Asia to the United States and from the United States to Europe — and have a negative impact on air quality far from their original sources, says a new report by the National Research Council.  Although degraded air quality is nearly always dominated by local emissions, the influence of non-domestic pollution sources may grow as emissions from developing countries increase and become relatively more important as a result of tightening environmental protection standards in industrialized countries.  

“Air pollution does not recognize national borders; the atmosphere connects distant regions of our planet,” said Charles Kolb, chair of the committee that wrote the report and president and chief executive officer of Aerodyne Research Inc.  “Emissions within any one country can affect human and ecosystem health in countries far downwind.  While it is difficult to quantify these influences, in some cases the impacts are significant from regulatory and public health perspectives.” 

The report examines four types of air pollutants: ozone; particulate matter such as dust, sulfates, or soot; mercury; and persistent organic pollutants such as DDT.  The committee found evidence, including satellite observations, that these four types of pollutants can be transported aloft across the Northern Hemisphere, delivering significant concentrations to downwind continents.  Ultimately, most pollutants’ impacts depend on how they filter down to the surface.  

Current limitations in modeling and observational capabilities make it difficult to determine how global sources of pollution affect air quality and ecosystems in downwind locations and distinguish the domestic and foreign components of observed pollutants.  Yet, some pollutant plumes observed in the U.S. can be attributed unambiguously to sources in Asia based on meteorological and chemical analyses, the committee said.  For example, one study found that a polluted airmass detected at Mt. Bachelor Observatory in central Oregon took approximately eight days to travel from East Asia.  

The health impacts of long-range transport vary by pollutant.  For ozone and particulate matter — which cause respiratory problems and other health effects — the main concern is direct inhalation.  While the amount of ozone and particulate matter transported on international scales is generally quite small compared with domestic sources, neither of these pollutants has a known “threshold,” or concentration below which exposure poses no risk for health impacts.  Therefore, even small incremental increases in atmospheric concentrations can have negative impacts, the committee said.  For instance, modeling studies have estimated that about 500 premature cardiopulmonary deaths could be avoided annually in North America by reducing ozone precursor emissions by 20 percent in the other major industrial regions of the Northern Hemisphere. 

For mercury and persistent organic pollutants, the main health concern is that their transport and deposition leads to gradual accumulation on land and in watersheds, creating an increase in human exposure via the food chain.  For example, people may consume mercury by eating fish.  There is also concern about eventual re-release of “legacy” emissions that have been stored in soils, forests, snowpacks, and other environmental reservoirs. 

In addition, the committee said that projected climate change will lead to a warmer climate and shifts in atmospheric circulation, likely affecting the patterns of emission, transport, transformation, and deposition for all types of pollution.  However, predicting the net impacts of the potential changes is extremely difficult with present knowledge. 

In the coming decades, man-made emissions are expected to rise in East Asia, the report says.  These increases could potentially be mitigated by increasingly stringent pollution control efforts and international cooperation in developing and deploying pollution control technology. 

To enhance understanding of long-range transport of pollution and its impacts, the committee recommended a variety of research initiatives, such as advancing “fingerprinting” techniques to better identify source-specific pollutant characteristics, and examining how emissions from ships and aircraft affect atmospheric composition and complicate the detection of pollution from land-based sources.  The committee emphasized developing an integrated “pollution source-attribution” system that improves capabilities in emissions measurements and estimates; atmospheric chemical and meteorological modeling; long-term, ground-based observations; satellite remote sensing; and process-focused field studies.  

Moreover, the committee stressed that the United States, as both a source and receptor of long-range pollution, has an interest in remaining actively engaged in air pollutants that travel abroad, including support of more extensive international cooperation in research, assessment, and emissions control efforts. 

The report was sponsored by the U.S. Environmental Protection Agency, National Oceanic and Atmospheric Administration, NASA, and National Science Foundation.  The National Academy of Sciences, National Academy of Engineering, Institute of Medicine, and National Research Council make up the National Academies.  They are independent, nonprofit institutions that provide science, technology, and health policy advice under an 1863 congressional charter.  Committee members, who serve pro bono as volunteers, are chosen by the Academies for each study based on their expertise and experience and must satisfy the Academies’ conflict-of-interest standards.  The resulting consensus reports undergo external peer review before completion.  For more information, visit National Academies  A committee roster follows. 

Reference: National Academy of Sciences, Air Pollutants From Abroad a Growing Concern, Says New Report, Washington, September 29. 2009

Effects of the endocrine disruptors Atrazine and PCB on human cells

New findings show effects on human cells from PCBs and Atrazine

Polychlorinated biphenyls (PCBs) and a number of pesticides can act as endocrine disrupting compounds (EDCs). These molecules exhibit hormonal activity in vivo, and can therefore interact and perturb normal physiological functions. Many of these compounds are persistent in the environment, and their bioaccumulation may constitute a significant threat for human health. 

Physiological abnormalities following exposure to these xenobiotic compounds go along with alterations at the protein level of individual cells. In this study, MCF-7 cells were exposed to environmentally relevant concentrations of atrazine, PCB153 (100ppb, respectively), 17-ss estradiol (positive control, 10nM) and a negative control (solvent) for t=24h (n=3 replicates/exposure group). After trizol extraction and protein solubilisation, protein expression levels were studied by 2D-DiGE. Proteins differentially expressed were excised, trypsin-digested, and identified by MALDI-ToF-ToF, followed by NCBInr database search. 2D-DiGE experiments demonstrated that 49 spots corresponding to 29 proteins were significantly differentially expressed in MCF-7 cells (>1.5 fold, P<0.05, Student’s paired T-test). 

These proteins belonged to various cellular compartments (nucleus, cytosol, membrane), and varied in function; 88% of proteins were down-regulated during atrazine exposure whereas 75% of proteins were up-regulated by PCB153. Affected proteins included those regulating oxidative stress such as superoxide dismutase and structural proteins such as actin or tropomyosin, which may explain morphological changes of cells already observed under the microscope. This study highlights the susceptibility of human cells to compounds with endocrine disrupting properties. 

Reference: Lasserre JP, Fack F, Revets D, Planchon S, Renaut J, Hoffmann L, Gutleb AC, Muller CP, Torsten B., Effects of the endocrine disruptors Atrazine and PCB 153 on the Protein Expression of MCF-7 human cells, J Proteome Res. 2009 Sep 25.

Genetic rat model of cholinergic hypersensitivity: implications for chemical intolerance, chronic fatigue, and asthma

Lab Rats show Model for Chemical Sensitivity

The fact that only some individuals exposed to environmental chemicals develop chemical intolerance raises the possibility that genetic factors could be contributing factors. The present communication summarizes evidence from a genetic animal model of cholinergic supersensitivity that suggests that an abnormal cholinergic system could be one predisposing genetic factor.

The Flinders Sensitive Line (FSL) rats were established by selective breeding for increased responses to an organophosphate. It was subsequently found that these FSL rats were also more sensitive to direct-acting muscarinic agonists and had elevated muscarinic receptors compared to the selectively bred parallel group, the Flinders Resistant Line (FRL) rats, or randomly bred control rats.

Increased sensitivity to cholinergic agents has also been observed in several human populations, including individuals suffering from chemical intolerance. Indeed, the FSL rats exhibit certain behavioral characteristics such as abnormal sleep, activity, and appetite that are similar to those reported in these human populations. In addition, the FSL rats have been reported to exhibit increased sensitivity to a variety of other chemical agents. Peripheral tissues, such as intestinal and airway smooth muscle, appear to be more sensitive to both cholinergic agonists and an antigen, ovalbumin. Hypothermia, a centrally mediated response, is more pronounced in the FSL rats after nicotine and alcohol, as well as agents that are selective for the dopaminergic and serotonergic systems.

In some cases, the increased sensitivity has been detected in the absence of any changes in the receptors with which the drugs interact (dopamine receptors), while receptor changes have been seen in other cases (nicotine receptors). Therefore, there may be multiple mechanisms underlying the multiple chemical sensitivity-chemical intolerance of the FSL rats. An elucidation of these mechanisms may provide useful clues to those involved in chemical intolerance in humans. 

Reference: Overstreet DH, Djuric V., A genetic rat model of cholinergic hypersensitivity: implications for chemical intolerance, chronic fatigue, and asthma, University of North Carolina, Ann N Y Acad Sci. 2001 Mar;933:92-102.

Environmental chemicals found in breast milk and high incidence of testicular cancer

Chemical Contamination affects Generations

High levels of persistent environmental chemicals found in breast milk in a population with many male reproductive problems 

A comparison of breast milk samples from Denmark and Finland revealed a significant difference in environmental chemicals which have previously been implicated in testicular cancer or in adversely affecting development of the fetal testis in humans and animals. This finding is published today in the International Journal of Andrology. 

In recent years a worldwide increase in testicular cancer has been noticed, but the cause remains unknown. In some countries, such as Denmark the prevalence of this disease and other male reproductive disorders, including poor semen quality and congenital genital abnormalities is conspicuously high; while in Finland, a similarly industrialized Nordic country, the incidences of these disorders are markedly lower. In the UK, almost 2,000 men are diagnosed with testicular cancer every year, and in the US this number is over 8,000. There is a wide variation in incidence rates of testicular cancer around the globe, and the reasons behind the observed trends are unexplained. 

Environmental endocrine disrupting chemicals (EDCs) are commonly found in fatty foods, paints, plasticizers, pesticides, and the byproducts of industrial processes, and in recent studies an association has been shown between some of these agents and male reproductive problems. To investigate whether EDCs could be related to such great differences in reproductive disorders between closely related countries, Konrad Krysiak-Baltyn and colleagues from Denmark, Finland, and Germany measured levels of 121 chemicals in 68 breast milk samples from Denmark and Finland to compare exposure of mothers to EDCs. 

With so many chemicals, they used sophisticated, bioinformatics tools to interpret the complex data, and the results showed a clear distinction between the countries. 

“We were very surprised to find that some EDC levels, including some dioxins, PCBs and some pesticides, were significantly higher in Denmark than in Finland,” said Professor Niels Skakkebaek, a senior member of the research team, based at the University Department of Growth and Reproduction, Rigshospitalet, Denmark. “Our findings reinforce the view that environmental exposure to EDCs may explain some of the temporal and between-country differences in incidence of male reproductive disorders.”

“In spite of the findings, I would strongly urge women, including Danish mothers, to continue with breast feeding, which has many beneficial effects for the child,” added Skakkebaek. 

Reference: Wiley-Blackwell, Environmental chemicals found in breast milk and high incidence of testicular cancer, September 24, 2009