scholarly journals Formation of hydroxyl radical from San Joaquin Valley particles extracted in a cell-free solution

2011 ◽  
Vol 11 (6) ◽  
pp. 16861-16894 ◽  
Author(s):  
H. Shen ◽  
C. Anastasio
Keyword(s):  
Hydroxyl Radical ◽  
Dominant Role ◽  
San Joaquin Valley ◽  
Ambient Particulate Matter ◽  
Adverse Health Effects ◽  
Quantitative Studies ◽  
A Cell ◽  
Lung Lining Fluid ◽  
Phosphate Buffered Saline

Abstract. Previous studies have suggested that the adverse health effects from ambient particulate matter (PM) are linked to the formation of reactive oxygen species (ROS) by PM. While hydroxyl radical (•OH) is the most reactive of the ROS species, there are few quantitative studies of •OH generation from PM. Here we report on •OH formation from PM collected at an urban (Fresno) and rural (Westside) site in the San Joaquin Valley (SJV) of California. We quantified •OH in PM extracts using a cell-free, phosphate-buffered saline (PBS) solution with or without 50 μM ascorbate (Asc). The results show that generally the urban Fresno PM generates much more •OH than the rural Westside PM. The presence of Asc at a physiologically relevant concentration in the extraction solution greatly enhances •OH formation from all the samples. Fine PM (PM2.5) generally makes more •OH than the corresponding coarse PM (PMcf, i.e., 2.5 to 10 μm) normalized by air volume collected, while the coarse PM typically generates more •OH normalized by PM mass. •OH production by SJV PM is reduced on average by (97 ± 6) % when the transition metal chelator desferoxamine (DSF) is added to the extraction solution, indicating a dominant role of transition metals. By measuring calibration curves of •OH generation from copper and iron, and quantifying copper and iron concentrations in our particle extracts, we find that PBS-soluble copper is primarily responsible for •OH production by the SJV PM, while iron often makes a significant contribution. Extrapolating our results to expected burdens of PM-derived •OH in human lung lining fluid suggests that typical daily PM exposures in the San Joaquin Valley are unlikely to result in a high amount of pulmonary •OH, although high PM events could produce much higher levels of •OH, which might lead to cytotoxicity.

scholarly journals Formation of hydroxyl radical from San Joaquin Valley particles extracted in a cell-free surrogate lung fluid

2011 ◽  
Vol 11 (18) ◽  
pp. 9671-9682 ◽  
Author(s):  
H. Shen ◽  
C. Anastasio
Keyword(s):  
Hydroxyl Radical ◽  
Dominant Role ◽  
San Joaquin Valley ◽  
Lung Fluid ◽  
Adverse Health Effects ◽  
Quantitative Studies ◽  
A Cell ◽  
Lung Lining Fluid ◽  
Phosphate Buffered Saline

Abstract. Previous studies have suggested that the adverse health effects from ambient particulate matter (PM) are linked to the formation of reactive oxygen species (ROS) by PM in cardiopulmonary tissues. While hydroxyl radical (•OH) is the most reactive of the ROS species, there are few quantitative studies of •OH generation from PM. Here we report on •OH formation from PM collected at an urban (Fresno) and rural (Westside) site in the San Joaquin Valley (SJV) of California. We quantified •OH in PM extracts using a cell-free, phosphate-buffered saline (PBS) solution with or without 50 μM ascorbate (Asc). The results show that generally the urban Fresno PM generates much more •OH than the rural Westside PM. The presence of Asc at a physiologically relevant concentration in the extraction solution greatly enhances •OH formation from all the samples. Fine PM (PM2.5) generally makes more •OH than the corresponding coarse PM (PMcf, i.e. with diameters of 2.5 to 10 μm) normalized by air volume collected, while the coarse PM typically generates more •OH normalized by PM mass. •OH production by SJV PM is reduced on average by (97 ± 6) % when the transition metal chelator desferoxamine (DSF) is added to the extraction solution, indicating a dominant role of transition metals. By measuring calibration curves of •OH generation from copper and iron, and quantifying copper and iron concentrations in our particle extracts, we find that PBS-soluble copper is primarily responsible for •OH production by the SJV PM, while iron often makes a significant contribution. Extrapolating our results to expected burdens of PM-derived •OH in human lung lining fluid suggests that typical daily PM exposures in the San Joaquin Valley are unlikely to result in a high amount of pulmonary •OH, although high PM events could produce much higher levels of •OH, which might lead to cytotoxicity.

scholarly journals Generation of hydrogen peroxide from San Joaquin Valley particles in a cell-free solution

2011 ◽  
Vol 11 (2) ◽  
pp. 753-765 ◽  
Author(s):  
H. Shen ◽  
A. I. Barakat ◽  
C. Anastasio
Keyword(s):  
Hydrogen Peroxide ◽  
Health Effects ◽  
Dominant Role ◽  
Epidemiological Studies ◽  
San Joaquin Valley ◽  
Ambient Particulate Matter ◽  
Adverse Health Effects ◽  
A Cell ◽  
Lung Lining Fluid ◽  
Phosphate Buffered Saline

Abstract. Epidemiological studies have shown a correlation between exposure to ambient particulate matter (PM) and adverse health effects. One proposed mechanism of PM-mediated health effects is the generation of reactive oxygen species (ROS) – e.g., superoxide (•O2−), hydrogen peroxide (HOOH), and hydroxyl radical (•OH) – followed by oxidative stress. There are very few quantitative, specific measures of individual ROS generated from PM, but this information would help to more quantitatively address the link between ROS and the health effects of PM. To address this gap, we quantified the generation of HOOH by PM collected at an urban (Fresno) and rural (Westside) site in the San Joaquin Valley (SJV) of California during summer and winter from 2006 to 2009. HOOH was quantified by HPLC after extracting the PM in a cell-free, phosphate-buffered saline (PBS) solution with or without 50 μM ascorbate (Asc). Our results show that the urban PM generally generates much more HOOH than the rural PM but that there is no apparent seasonal difference in HOOH generation. In nearly all of the samples the addition of a physiologically relevant concentration of Asc greatly enhances HOOH formation, but a few of the coarse PM samples were able to generate a considerable amount of HOOH in the absence of added Asc, indicating the presence of unknown reductants. Normalized by air volume, the fine PM (PM2.5) generally makes more HOOH than the corresponding coarse PM (PMcf, i.e., 2.5 to 10 μm), primarily because the mass concentration of PM2.5 is much higher than that of PMcf. However, normalized by PM mass, the coarse PM typically generates more HOOH than the fine PM. The amount of HOOH produced by SJV PM is reduced on average by (78 ± 15)% when the transition metal chelator desferoxamine (DSF) is added to the extraction solution, indicating that transition metals play a dominant role in HOOH generation. By measuring calibration curves of HOOH generation from copper, and quantifying copper concentrations in our particle extracts, we find that PBS-soluble copper is primarily responsible for HOOH production by the Fresno PM. Extrapolating our results to expected concentrations of PM-derived HOOH in human lung lining fluid suggests that typical daily PM exposures in the San Joaquin Valley are unlikely to cause HOOH-mediated acute health effects, but that very high PM events might lead to cytotoxic levels of pulmonary HOOH.

scholarly journals Generation of hydrogen peroxide from San Joaquin Valley particles in a cell-free solution

2010 ◽  
Vol 10 (9) ◽  
pp. 21323-21356 ◽  
Author(s):  
H. Shen ◽  
A. I. Barakat ◽  
C. Anastasio
Keyword(s):  
Hydrogen Peroxide ◽  
Health Effects ◽  
Dominant Role ◽  
Epidemiological Studies ◽  
San Joaquin Valley ◽  
Ambient Particulate Matter ◽  
Adverse Health Effects ◽  
Human Lungs ◽  
A Cell ◽  
Phosphate Buffered Saline

Abstract. Epidemiological studies have shown a correlation between exposure to ambient particulate matter (PM) and adverse health effects. One proposed mechanism of PM-mediated health effects is the generation of reactive oxygen species (ROS) – e.g., superoxide (•O2−), hydrogen peroxide (HOOH), and hydroxyl radical (•OH) – followed by oxidative stress. There are very few quantitative, specific measures of individual ROS generated from PM, but this information would help to more quantitatively address the link between ROS and the health effects of PM. To address this gap, we quantified the generation of HOOH by PM collected at an urban (Fresno) and rural (Westside) site in the San Joaquin Valley (SJV) of California during summer and winter from 2006 to 2009. HOOH was quantified by HPLC after extracting the PM in a cell-free, phosphate-buffered saline (PBS) solution with or without 50 μM ascorbate (Asc). Our results show that the urban PM generally generates much more HOOH than the rural PM but that there is no apparent seasonal difference in HOOH generation. In nearly all of the samples the addition of a physiologically relevant concentration of Asc greatly enhances HOOH formation, but a few of the coarse PM samples were able to generate a considerable amount of HOOH in the absence of added Asc, indicating the presence of unknown reductants. Normalized by air volume, the fine PM (PM2.5) generally makes more HOOH than the corresponding coarse PM (PMcf, i.e., 2.5 to 10 μm), primarily because the mass concentration of PM2.5 is much higher than that of PMcf. However, normalized by PM mass, the coarse PM typically generates more HOOH than the fine PM. The amount of HOOH produced by SJV PM is reduced on average by (78±15)% when the transition metal chelator desferoxamine (DSF) is added to the extraction solution, indicating that transition metals play a dominant role in HOOH generation. By measuring calibration curves of HOOH generation from copper, and quantifying copper concentrations in our particle extracts, we find that PBS-soluble copper is primarily responsible for HOOH production by the Fresno PM. Extrapolating our results to expected concentrations of PM-derived HOOH in human lungs suggests that typical daily PM exposures in the San Joaquin Valley are unlikely to cause HOOH-mediated acute health effects, but that very high PM events might lead to cytotoxic levels of pulmonary HOOH.

scholarly journals Laccase Protects Cryptococcus neoformansfrom Antifungal Activity of Alveolar Macrophages

1999 ◽  
Vol 67 (11) ◽  
pp. 6034-6039 ◽  
Author(s):  
Lide Liu ◽  
Ram P. Tewari ◽  
Peter R. Williamson
Keyword(s):  
Antifungal Activity ◽  
Hydroxyl Radical ◽  
Oxidase Activity ◽  
Radical Scavenger ◽  
Free System ◽  
Recombinant Laccase ◽  
Hydroxyl Radical Scavenger ◽  
A Cell ◽  
The Difference

ABSTRACT While laccase of Cryptococcus neoformans is implicated in the virulence of the organism, our recent studies showing absence of melanin in the infected mouse brain has led us to a search for alternative roles for laccase in cryptococcosis. We investigated the role of laccase in protection of C. neoformans against murine alveolar macrophage (AM)-mediated antifungal activity by using a pair of congenic laccase-positive (2E-TUC) and laccase-deficient (2E-TU) strains. The laccase-positive cells with laccase derepression were more resistant to the antifungal activity of AM than a laccase-deficient strain ([28.9 ± 1.2]% versus [40.2 ± 2.6]% killing). Addition of l-dopa toCryptococcus to produce melanin in a laccase-positive strain resulted in a slight increase in protection of C. neoformans from the antifungal activity of macrophages ([25.4 ± 3.4]% versus [28.9 ± 1.2]% killing). Recombinant cryptococcal laccase exhibited iron oxidase activity in converting Fe(II) to Fe(III). Moreover, recombinant laccase inhibited killing of C. neoformans by hydroxyl radicals catalyzed by iron in a cell-free system. Addition of the hydroxyl radical scavenger mannitol or dimethyl sulfoxide to AMs prior to the introduction of cryptococcal cells decreased killing of both strains and reduced the difference in susceptibility between the laccase-positive and laccase-deficient strains. Furthermore, laccase-mediated protection from AM killing was inhibited by the addition of Fe(II), presumably by overcoming the effects of the iron oxidase activity of cryptococcal laccase. These results suggest that the iron oxidase activity of laccase may protect C. neoformans from macrophages by oxidation of phagosomal iron to Fe(III) with a resultant decrease in hydroxyl radical formation.

scholarly journals Dominant Role of PI3K p110α over p110β in Insulin and β-Adrenergic Receptor Signalling

2021 ◽  
Vol 22 (23) ◽  
pp. 12813
Author(s):  
Biqin Zhang ◽  
Cheukyau Luk ◽  
Joyce Valadares ◽  
Christos Aronis ◽  
Lazaros C. Foukas
Keyword(s):  
Insulin Receptor ◽  
Adrenergic Receptor ◽  
Metabolic Regulation ◽  
Insulin Signalling ◽  
Dominant Role ◽  
Selective Inhibitors ◽  
Relative Contribution ◽  
Regulation Of Metabolism ◽  
A Cell

Attribution of specific roles to the two ubiquitously expressed PI 3-kinase (PI3K) isoforms p110α and p110β in biological functions they have been implicated, such as in insulin signalling, has been challenging. While p110α has been demonstrated to be the principal isoform activated downstream of the insulin receptor, several studies have provided evidence for a role of p110β. Here we have used isoform-selective inhibitors to estimate the relative contribution of each of these isoforms in insulin signalling in adipocytes, which are a cell type with essential roles in regulation of metabolism at the systemic level. Consistent with previous genetic and pharmacological studies, we found that p110α is the principal isoform activated downstream of the insulin receptor under physiological conditions. p110α interaction with Ras enhanced the strength of p110α activation by insulin. However, this interaction did not account for the selectivity for p110α over p110β in insulin signalling. We also demonstrate that p110α is the principal isoform activated downstream of the β-adrenergic receptor (β-AR), another important signalling pathway in metabolic regulation, through a mechanism involving activation of the cAMP effector molecule EPAC1. This study offers further insights in the role of PI3K isoforms in the regulation of energy metabolism with implications for the therapeutic application of selective inhibitors of these isoforms.

Activation of cytochrome c to a peroxidase compound I-type intermediate by H2O2: relevance to redox signalling in apoptosis

2004 ◽  
Vol 71 ◽  
pp. 97-106 ◽  
Author(s):  
Mark Burkitt ◽  
Clare Jones ◽  
Andrew Lawrence ◽  
Peter Wardman
Keyword(s):  
Cytochrome C ◽  
Hydroxyl Radical ◽  
Redox Regulation ◽  
Chemotherapeutic Agents ◽  
Tyrosyl Radical ◽  
Compound I ◽  
Definitive Evidence ◽  
Enhanced Production ◽  
Physico Chemical

The release of cytochrome c from mitochondria during apoptosis results in the enhanced production of superoxide radicals, which are converted to H2O2 by Mn-superoxide dismutase. We have been concerned with the role of cytochrome c/H2O2 in the induction of oxidative stress during apoptosis. Our initial studies showed that cytochrome c is a potent catalyst of 2′,7′-dichlorofluorescin oxidation, thereby explaining the increased rate of production of the fluorophore 2′,7′-dichlorofluorescein in apoptotic cells. Although it has been speculated that the oxidizing species may be a ferryl-haem intermediate, no definitive evidence for the formation of such a species has been reported. Alternatively, it is possible that the hydroxyl radical may be generated, as seen in the reaction of certain iron chelates with H2O2. By examining the effects of radical scavengers on 2′,7′-dichlorofluorescin oxidation by cytochrome c/H2O2, together with complementary EPR studies, we have demonstrated that the hydroxyl radical is not generated. Our findings point, instead, to the formation of a peroxidase compound I species, with one oxidizing equivalent present as an oxo-ferryl haem intermediate and the other as the tyrosyl radical identified by Barr and colleagues [Barr, Gunther, Deterding, Tomer and Mason (1996) J. Biol. Chem. 271, 15498-15503]. Studies with spin traps indicated that the oxo-ferryl haem is the active oxidant. These findings provide a physico-chemical basis for the redox changes that occur during apoptosis. Excessive changes (possibly catalysed by cytochrome c) may have implications for the redox regulation of cell death, including the sensitivity of tumour cells to chemotherapeutic agents.

Chronic Pain: Fundamental Scientific Considerations, Specifically for Legal Claims

2013 ◽  
Vol 18 (1) ◽  
pp. 1-18 ◽  
Author(s):  
Robert J. Barth
Keyword(s):  
Health Outcomes ◽  
Pain Perception ◽  
Driving Forces ◽  
Psychological Treatment ◽  
Dominant Role ◽  
Meta Analysis ◽  
General Medicine ◽  
Pain Syndrome ◽  
Problematic Relationship

Abstract Scientific findings have indicated that psychological and social factors are the driving forces behind most chronic benign pain presentations, especially in a claim context, and are relevant to at least three of the AMA Guides publications: AMA Guides to Evaluation of Disease and Injury Causation, AMA Guides to Work Ability and Return to Work, and AMA Guides to the Evaluation of Permanent Impairment. The author reviews and summarizes studies that have identified the dominant role of financial, psychological, and other non–general medicine factors in patients who report low back pain. For example, one meta-analysis found that compensation results in an increase in pain perception and a reduction in the ability to benefit from medical and psychological treatment. Other studies have found a correlation between the level of compensation and health outcomes (greater compensation is associated with worse outcomes), and legal systems that discourage compensation for pain produce better health outcomes. One study found that, among persons with carpal tunnel syndrome, claimants had worse outcomes than nonclaimants despite receiving more treatment; another examined the problematic relationship between complex regional pain syndrome (CRPS) and compensation and found that cases of CRPS are dominated by legal claims, a disparity that highlights the dominant role of compensation. Workers’ compensation claimants are almost never evaluated for personality disorders or mental illness. The article concludes with recommendations that evaluators can consider in individual cases.

НЕКОТОРЫЕ ОСОБЕННОСТИ РАСПРОСТРАНЕННОСТИ РЕСПИРАТОРНОЙ АЛЛЕРГИИ НА ЮГЕ РОССИИ

2019 ◽  
Author(s):  
D.Sh. Macharadze
Keyword(s):  
Dominant Role ◽  
Pollen Allergy ◽  
Respiratory Allergy ◽  
House Dust Mites ◽  
Dust Mites ◽  
The Past ◽  
Regional Features ◽  
Respiratory Allergies ◽  
Southern Russia

В обзорной статье приведены данные по распространенности респираторной аллергии - аллергического ринита и бронхиальной астмы на юге России, опубликованные за последние десятилетия. Показана доминирующая роль пыльцевой аллергии практически во всем южном регионе России. В Чеченской Республике у больных респираторной аллергией обнаружена сходная частота встречаемости сенсибилизации к клещам домашней пыли и пыльце злаковых трав (51,1 и 52,5 соответственно), тогда как сенсибилизация к пыльце амброзии и полыни встречалась в 3 раза реже (26,6 и 20,7 соответственно) по сравнению с соседними регионами юга России. Эти данные демонстрируют климатогеографические, экологические и другие региональные особенности в распространении респираторной аллергии.The review article presents data on the prevalence of respiratory allergy - allergic rhinitis and bronchial asthma in southern Russia, published over the past decades. The dominant role of pollen allergy is shown in almost the entire southern region of Russia. In the Chechen Republic, sensitization to house dust mites and grass pollen was found in patients with respiratory allergy equally (51.1 and 52.5, respectively), whereas ragweed and mugwort sensitization was 3 times less (26.6 and 20.7, respectively) compared with the neighboring regions of southern Russia. These data demonstrate climate-geographical, environmental and other regional features in the prevalence of respiratory allergies.

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