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1.
Sci Rep ; 13(1): 13201, 2023 Aug 14.
Article En | MEDLINE | ID: mdl-37580480

Exposure to particulate matter less than 2.5 µm in diameter (PM2.5) is a cause of concern in cities and major emission regions of northern India. An intensive field campaign involving the states of Punjab, Haryana and Delhi national capital region (NCR) was conducted in 2022 using 29 Compact and Useful PM2.5 Instrument with Gas sensors (CUPI-Gs). Continuous observations show that the PM2.5 in the region increased gradually from < 60 µg m-3 in 6-10 October to up to 500 µg m-3 on 5-9 November, which subsequently decreased to about 100 µg m-3 in 20-30 November. Two distinct plumes of PM2.5 over 500 µg m-3 are tracked from crop residue burning in Punjab to Delhi NCR on 2-3 November and 10-11 November with delays of 1 and 3 days, respectively. Experimental campaign demonstrates the advantages of source region observations to link agricultural waste burning and air pollution at local to regional scales.

2.
Sci Rep ; 11(1): 23378, 2021 12 16.
Article En | MEDLINE | ID: mdl-34916540

Emissions of black carbon (BC) particles from anthropogenic and natural sources contribute to climate change and human health impacts. Therefore, they need to be accurately quantified to develop an effective mitigation strategy. Although the spread of the emission flux estimates for China have recently narrowed under the constraints of atmospheric observations, consensus has not been reached regarding the dominant emission sector. Here, we quantified the contribution of the residential sector, as 64% (44-82%) in 2019, using the response of the observed atmospheric concentration in the outflowing air during Feb-Mar 2020, with the prevalence of the COVID-19 pandemic and restricted human activities over China. In detail, the BC emission fluxes, estimated after removing effects from meteorological variability, dropped only slightly (- 18%) during Feb-Mar 2020 from the levels in the previous year for selected air masses of Chinese origin, suggesting the contributions from the transport and industry sectors (36%) were smaller than the rest from the residential sector (64%). Carbon monoxide (CO) behaved differently, with larger emission reductions (- 35%) in the period Feb-Mar 2020, suggesting dominance of non-residential (i.e., transport and industry) sectors, which contributed 70% (48-100%) emission during 2019. The estimated BC/CO emission ratio for these sectors will help to further constrain bottom-up emission inventories. We comprehensively provide a clear scientific evidence supporting mitigation policies targeting reduction in residential BC emissions from China by demonstrating the economic feasibility using marginal abatement cost curves.


Air Pollutants/analysis , Air Pollution/analysis , COVID-19/prevention & control , Particulate Matter/analysis , SARS-CoV-2/isolation & purification , Soot/analysis , Algorithms , Atmosphere/analysis , COVID-19/epidemiology , COVID-19/virology , China , Climate Change , Environmental Monitoring/methods , Environmental Monitoring/statistics & numerical data , Geography , Human Activities , Humans , Models, Theoretical , Pandemics , Residence Characteristics , SARS-CoV-2/physiology , Seasons , Wind
3.
Sci Rep ; 11(1): 9800, 2021 05 07.
Article En | MEDLINE | ID: mdl-33963208

COVID-19 related restrictions lowered particulate matter and trace gas concentrations across cities around the world, providing a natural opportunity to study effects of anthropogenic activities on emissions of air pollutants. In this paper, the impact of sudden suspension of human activities on air pollution was analyzed by studying the change in satellite retrieved NO2 concentrations and top-down NOx emission over the urban and rural areas around Delhi. NO2 was chosen for being the most indicative of emission intensity due to its short lifetime of the order of a few hours in the planetary boundary layer. We present a robust temporal comparison of Ozone Monitoring Instrument (OMI) retrieved NO2 column density during the lockdown with the counterfactual baseline concentrations, extrapolated from the long-term trend and seasonal cycle components of NO2 using observations during 2015 to 2019. NO2 concentration in the urban area of Delhi experienced an anomalous relative change ranging from 60.0% decline during the Phase 1 of lockdown (March 25-April 13, 2020) to 3.4% during the post-lockdown Phase 5. In contrast, we find no substantial reduction in NO2 concentrations over the rural areas. To segregate the impact of the lockdown from the meteorology, weekly top-down NOx emissions were estimated from high-resolution TROPOspheric Monitoring Instrument (TROPOMI) retrieved NO2 by accounting for horizontal advection derived from the steady state continuity equation. NOx emissions from urban Delhi and power plants exhibited a mean decline of 72.2% and 53.4% respectively in Phase 1 compared to the pre-lockdown business-as-usual phase. Emission estimates over urban areas and power-plants showed a good correlation with activity reports, suggesting the applicability of this approach for studying emission changes. A higher anomaly in emission estimates suggests that comparison of only concentration change, without accounting for the dynamical and photochemical conditions, may mislead evaluation of lockdown impact. Our results shall also have a broader impact for optimizing bottom-up emission inventories.


Air Pollutants/analysis , Air Pollution/analysis , COVID-19/prevention & control , Communicable Disease Control , Environmental Monitoring , Nitrogen Dioxide/analysis , COVID-19/epidemiology , Cities , Humans , India/epidemiology , Nitrogen Oxides/analysis , SARS-CoV-2/isolation & purification
4.
Sci Rep ; 10(1): 13442, 2020 08 10.
Article En | MEDLINE | ID: mdl-32778673

Delhi, a tropical Indian megacity, experiences one of the most severe air pollution in the world, linked with diverse anthropogenic and biomass burning emissions. First phase of COVID-19 lockdown in India, implemented during 25 March to 14 April 2020 resulted in a dramatic near-zeroing of various activities (e.g. traffic, industries, constructions), except the "essential services". Here, we analysed variations in the fine particulate matter (PM2.5) over the Delhi-National Capital Region. Measurements revealed large reductions (by 40-70%) in PM2.5 during the first week of lockdown (25-31 March 2020) as compared to the pre-lockdown conditions. However, O3 pollution remained high during the lockdown due to non-linear chemistry and dynamics under low aerosol loading. Notably, events of enhanced PM2.5 levels (300-400 µg m-3) were observed during night and early morning hours in the first week of April after air temperatures fell close to the dew-point (~ 15-17 °C). A haze formation mechanism is suggested through uplifting of fine particles, which is reinforced by condensation of moisture following the sunrise. The study highlights a highly complex interplay between the baseline pollution and meteorology leading to counter intuitive enhancements in pollution, besides an overall improvement in air quality during the COVID-19 lockdown in this part of the world.


Air Pollutants/analysis , Betacoronavirus , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Particulate Matter/analysis , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , Quarantine/methods , Weather , Aerosols/analysis , Air Pollution/analysis , COVID-19 , Cities/epidemiology , Coronavirus Infections/virology , Environmental Monitoring/methods , Humans , India/epidemiology , Ozone/analysis , Pneumonia, Viral/virology , SARS-CoV-2 , Temperature
5.
Sci Rep ; 8(1): 9324, 2018 06 29.
Article En | MEDLINE | ID: mdl-29959366

The contribution of the atmospheric deposition of inorganic nitrogen compounds produced in East Asia to the marine ecosystems of the North Western Pacific Ocean (NWPO) was investigated in this study using a 3-D lower trophic-marine ecosystem model (NEMURO) combined with an atmospheric regional chemical transport model (WRF-CMAQ). The monthly mean values for the wet and dry deposition of nitrogen compounds, including gases (HNO3 and NH3) and aerosol particles (NO3- and NH4+), were determined using the WRF-CMAQ for the NWPO from 2009-2016. These values were input into the NEMURO as an additional nitrogen source. The NEMURO indicated that the annual average chlorophyll mass concentration at the surface in the subtropical region (20°N-30°N; 125°E-150°E) of the NWPO increased from 0.04 to 0.10 mg/m3. Similarly, the gross primary productivity, integrated over sea depths of 0-200 m, increased from 85 to 147 mg C/m2/day because of this deposition. This study indicates that the supply of atmospheric inorganic nitrogen compounds from East Asia to the NWPO could have a high nutrient impact on the marine ecosystem in the subtropical region.

6.
J Air Waste Manag Assoc ; 64(4): 374-87, 2014 Apr.
Article En | MEDLINE | ID: mdl-24843910

UNLABELLED: Improvement of air quality models is required so that they can be utilized to design effective control strategies for fine particulate matter (PM2.5). The Community Multiscale Air Quality modeling system was applied to the Greater Tokyo Area of Japan in winter 2010 and summer 2011. The model results were compared with observed concentrations of PM2.5 sulfate (SO4(2-)), nitrate (NO3(-)) and ammonium, and gaseous nitric acid (HNO3) and ammonia (NH3). The model approximately reproduced PM2.5 SO4(2-) concentration, but clearly overestimated PM2.5 NO3(-) concentration, which was attributed to overestimation of production of ammonium nitrate (NH4NO3). This study conducted sensitivity analyses of factors associated with the model performance for PM2.5 NO3(-) concentration, including temperature and relative humidity, emission of nitrogen oxides, seasonal variation of NH3 emission, HNO3 and NH3 dry deposition velocities, and heterogeneous reaction probability of dinitrogen pentoxide. Change in NH3 emission directly affected NH3 concentration, and substantially affected NH4NO3 concentration. Higher dry deposition velocities of HNO3 and NH3 led to substantial reductions of concentrations of the gaseous species and NH4NO3. Because uncertainties in NH3 emission and dry deposition processes are probably large, these processes may be key factors for improvement of the model performance for PM2.5 NO3(-). IMPLICATIONS: The Community Multiscale Air Quality modeling system clearly overestimated the concentration of fine particulate nitrate in the Greater Tokyo Area of Japan, which was attributed to overestimation of production of ammonium nitrate. Sensitivity analyses were conducted for factors associated with the model performance for nitrate. Ammonia emission and dry deposition of nitric acid and ammonia may be key factors for improvement of the model performance.


Air Pollutants/analysis , Ammonia/analysis , Environmental Monitoring , Nitrates/analysis , Nitric Acid/analysis , Particulate Matter/analysis , Sulfates/analysis , Atmosphere/chemistry , Humidity , Models, Theoretical , Particle Size , Seasons , Temperature , Tokyo , Wind
7.
J Air Waste Manag Assoc ; 64(4): 436-44, 2014 Apr.
Article En | MEDLINE | ID: mdl-24843914

UNLABELLED: NO2 vertical column densities (VCDs) over East Asia in June and December 2007 were simulated by the Community Multi-scale Air Quality (CMAQ) version 4.7.1 using an updated and more elaborate version of the Regional Emission Inventory in Asia (REAS) version 2. The modeling system could reasonably capture observed spatiotemporal changes of NO2 VCDs by satellite sensors, the Global Ozone Monitoring Experiment-2 (GOME-2), the Scanning Imaging Absorption Spectrometer for Atmospheric Cartography (SCIAMACHY), and the Ozone Monitoring Instrument (OMI), even at the coarsest horizontal resolution of 80 km. The CMAQ simulations were performed in a sequence of three horizontal resolutions (80 km, 40 km, and 20 km) for June and December 2007 to investigate the influence of changes of horizontal resolution on the obtained NO2 VCDs. CMAQ-simulated NO2 VCDs generally increased with improvements in resolution from 80 km to 40 km and then to 20 km. Increases in the CMAQ-simulated NO2 VCDs were greater for the change from 80 km to 40 km than for those from 40 km and 20 km, in which the increases of NO2 VCDs due to the improvement of horizontal resolution were approached convergence at the horizontal resolution of approximately 20 km. Conversely, no clear convergences in NO2 VCDs changes were found at near Tokyo and over the East China Sea. The biases of the NO2 VCDs simulated at a resolution of 20 km against the satellite retrievals were -36% near Beijing (CHN1) and -78% near Shanghai (CHN2) in summer; these errors were found to be comparable to the horizontal resolution-dependent errors, which were 18-25% at CHN1 and 44-58% at CHN2 from 80 km to 40 km. Conversely, the influence of changes of horizontal resolution in winter was relatively less compared to that in summer. IMPLICATIONS: NO2 VCDs over East Asia in June and December 2007 were simulated using CMAQ version 4.7.1 and REAS version 2. The modeling system could reasonably capture observed spatiotemporal changes of NO2 VCDs by satellite sensors. The CMAQ simulations were performed in a sequence of three horizontal resolutions, 80, 40, and 20 km, to investigate the influence of changes of horizontal resolution on the obtained NO2 VCDs. The results suggested that the influence of changes of horizontal resolution was larger in summer compared to that in winter. The magnitude of the influence was comparable to the biases of the NO2 VCDs simulated at a resolution of 20 km against the satellite retrievals.


Air Pollutants/analysis , Air Pollution/analysis , Environmental Monitoring , Nitrogen Dioxide/analysis , Ozone/analysis , Atmosphere/chemistry , China , Asia, Eastern , Models, Theoretical , Seasons , Spatio-Temporal Analysis
8.
J Air Waste Manag Assoc ; 64(4): 445-52, 2014 Apr.
Article En | MEDLINE | ID: mdl-24843915

UNLABELLED: The authors analyze the sensitivities of source regions in East Asia to PM2.5 (particulate matter with an aerodynamic diameter of < or = 2.5 microm) concentration at Fukue Island located in the western part of Japan by using a regional chemical transport model with emission sensitivity simulations for the year 2010. The temporal variations in PM2.5 concentration are generally reproduced, but the absolute concentration is underestimated by the model. Chemical composition of PM2.5 in the model is compared with filter sampling data in spring; simulated sulfate, ammonium, and elemental carbon are consistent with observations, but mass concentration of particulate organic matters is underestimated. The relative contribution from each source region shows the seasonal variation, especially in summer. The contribution from central north China (105 degrees E-124 degrees E, 34 degrees N-42 degrees N) accounts for 50-60% of PM2.5 at Fukue Island except in summer; it significantly decreases in summer (18%). Central south China (105 degrees E-123 degrees E, 26 degrees N-34 degrees N) has the relative contribution of 15-30%. The contribution from the Korean Peninsula is estimated at about 10% except in summer. The domestic contribution accounts for about 7% in spring and autumn and increases to 19% in summer. We also estimate the relative contribution to daily average concentration in high PM2.5 days (> 35 microg m(-3)). Central north China has a significant contribution of 60-70% except in summer. The relative contribution from central south China is estimated at 46% in summer and about 30% in the other seasons. The contributions from central north and south China on high PM2.5 days are generally larger than those of their seasonal mean contributions. The domestic contribution is smaller than the seasonal mean value in every season; it is less than 10% even in summer. These model results suggest that foreign anthropogenic sources have a substantial impact on attainment of the atmospheric environmental standard of Japan at Fukue Island. IMPLICATIONS: The contribution from several source regions in East Asia to PM2.5 concentration at Fukue Island, a remote island located in the western part of Japan and close to the Asian continent, is estimated using a three-dimensional chemical transport model. The model results suggest that PM2.5 that is attributed to foreign anthropogenic sources have a larger contribution than that of domestic pollution and have a substantial impact on attainment of the atmospheric environmental standard of Japan at Fukue Island.


Air Pollutants/analysis , Ammonium Compounds/analysis , Carbon/analysis , Environmental Monitoring , Particulate Matter/analysis , Sulfates/analysis , Atmosphere/chemistry , China , Asia, Eastern , Japan , Models, Theoretical , Particle Size , Seasons , Spatio-Temporal Analysis
9.
FEBS Lett ; 580(2): 613-9, 2006 Jan 23.
Article En | MEDLINE | ID: mdl-16406050

Anandamide (AEA) exhibits anti-inflammatory effects. However, its role in the periodontal field remains unknown. Here, we found that gingival crevicular fluid contained a detectable level of AEA. The cannabinoid receptors CB1 and CB2 were expressed by human gingival fibroblasts (HGFs), and markedly upregulated under pathological conditions. AEA significantly reduced the production of pro-inflammatory mediators (IL-6, IL-8 and MCP-1) induced by Porphyromonas gingivalis LPS in HGFs, and this effect was attenuated by AM251 and SR144528, selective antagonists of CB1 and CB2, respectively. Moreover, AEA completely blocked LPS-triggered NF-kappaB activation, implying that AEA may regulate hyperinflammatory reactions in periodontitis.


Arachidonic Acids/metabolism , Cannabinoid Receptor Modulators/metabolism , Endocannabinoids , Gingiva/metabolism , NF-kappa B/metabolism , Periodontitis , Signal Transduction/physiology , Cells, Cultured , Fibroblasts/cytology , Fibroblasts/drug effects , Fibroblasts/metabolism , Gingiva/chemistry , Gingiva/cytology , Gingiva/pathology , Gingival Crevicular Fluid/chemistry , Gingivitis/immunology , Gingivitis/pathology , Humans , Lipopolysaccharides/pharmacology , NF-kappa B/antagonists & inhibitors , Periodontitis/immunology , Periodontitis/pathology , Polyunsaturated Alkamides , Receptor, Cannabinoid, CB1/genetics , Receptor, Cannabinoid, CB1/metabolism , Receptor, Cannabinoid, CB2/genetics , Receptor, Cannabinoid, CB2/metabolism
10.
Pathophysiol Haemost Thromb ; 34(1): 41-7, 2005.
Article En | MEDLINE | ID: mdl-16293985

Thrombin, a serine protease that plays a pivotal role in blood coagulation, wound healing, and angiogenesis, has also been implicated in the mitogenesis of various cell types. Previously, we showed that thrombin and the thrombin receptor agonist peptide (TRAP-14; SFLLRNPNDKYEPF) for protease-activated receptor 1 (PAR1) induce vascular endothelial growth factor (VEGF) secretion in PC-12 cells. In this study, we show that thrombin and TRAP-14 also stimulate VEGF secretion in the human NB-1 neuroblastoma cells. In these cells, we further show that thrombin-induced VEGF secretion was blocked by cycloheximide and actinomycin D, indicating that de novo protein synthesis is essential for this process. Reduced thrombin-induced VEGF secretion upon treatment with LY294002, calphostin C, or BAPTA, further suggests that the process is dependent on phosphatidyl-inositol-3-kinase, protein kinase C, and calcium. However, the complete loss of thrombin-induced VEGF production upon treatment with argatroban, a derivative of arginine and a potent anticoagulant/antithrombin agent, supports the notion that argatroban serves as a useful therapeutic tool for thrombin-associated pathologic conditions. Here, it appears that argatroban may be effective in controlling disorders linked to thrombin-induced VEGF production in neuronal cells.


Hemostatics/pharmacology , Neuroblastoma/metabolism , Pipecolic Acids/pharmacology , Platelet Aggregation Inhibitors/pharmacology , Thrombin/pharmacology , Vascular Endothelial Growth Factor A/biosynthesis , Animals , Arginine/analogs & derivatives , Calcium/metabolism , Calcium Signaling/drug effects , Enzyme Inhibitors/pharmacology , Humans , PC12 Cells , Phosphatidylinositol 3-Kinases/metabolism , Protein Kinase C/metabolism , Rats , Sulfonamides
11.
Thromb Res ; 115(4): 319-25, 2005.
Article En | MEDLINE | ID: mdl-15668192

INTRODUCTION: Activated protein C (APC) is an important natural anticoagulant that is proteolytically generated from protein C (PC) by the modulation of thrombin activity in the presence of thrombomodulin on an endothelial surface. Recent studies have demonstrated that, beyond its anticoagulant acitivities, APC had anti-inflammatory and cytoprotective properties. The mechanisms underlying APC's anti-inflammatory effects remain unknown. Our goal was to elucidate and confirm these mechanisms. METHODS: We first examined the effect of APC on reactive oxygen species (ROS) and inflammatory cytokine production in murine macrophage-like RAW264.7 cells. We further examined the effect of APC on chemically induced lipid peroxidation and advanced glycation end-products (AGE) formation. RESULTS AND CONCLUSIONS: APC in the range of 10-50 microg/mL could reduce lipopolysaccharide (LPS)-induced ROS generation, nuclear factor kappaB (NF-kappaB) activation and resultant proinflammatory cytokine production. Additional cell-free experiments revealed that APC (10-50 microg/mL) had inhibitory effects on lipid peroxidation and AGE formation. These findings suggest that APC, via its intrinsic anti-oxidant properties, may, in settings of oxidant stress, exert important cytoprotective and anti-inflammatory effects that are distinct from its anticoagulant activity as an antioxidant protein. If that is true, APC may contribute to ROS-related chronic disorders including atherosclerosis and diabetes as well as acute shock conditions.


Anticoagulants/metabolism , Anticoagulants/pharmacology , Antioxidants/metabolism , Antioxidants/pharmacology , Glycation End Products, Advanced/biosynthesis , Lipid Peroxidation/drug effects , Protein C/metabolism , Protein C/pharmacology , Animals , Cell Line , Cell-Free System , Copper/pharmacology , Cytokines/biosynthesis , Inflammation Mediators/metabolism , Interleukin-1/biosynthesis , Lipopolysaccharides/pharmacology , Lipoproteins, LDL/metabolism , Mice , NF-kappa B/metabolism , Reactive Oxygen Species/metabolism , Tumor Necrosis Factor-alpha/biosynthesis
12.
Int J Food Sci Nutr ; 55(1): 61-6, 2004 Feb.
Article En | MEDLINE | ID: mdl-14630593

It has been suggested that oxidation of low-density lipoprotein (LDL) plays an important role in the initiation and progression of atherosclerosis. In the present study, we determined the anti-atherogenic effects of egg yolk-enriched garlic powder (EGP), which has been used as a traditional health-promoting food in southern Japan since ancient times, on LDL oxidation and oxidant stress-induced cell injury models. We confirmed that EGP inhibits copper-induced LDL oxidation in a dose-dependent manner. We also observed that pretreatment of EGP significantly suppressed the production of peroxides in HL60 cells and protected endothelial cells from hydrogen peroxide-induced cell injury. These findings might, in part, be ascribed to the biodistribution of garlic compounds and egg yolk interaction, and suggest that EGP might be useful in the prevention of atherosclerosis.


Egg Yolk/metabolism , Garlic/metabolism , Lipoproteins, LDL/metabolism , Oxidative Stress/physiology , Arteriosclerosis/metabolism , Arteriosclerosis/prevention & control , Biological Availability , Cell Survival/physiology , Endothelial Cells/metabolism , HL-60 Cells , Humans , Japan , Oxidation-Reduction , Reactive Oxygen Species/metabolism , Thiobarbituric Acid Reactive Substances/metabolism
13.
Hepatology ; 38(5): 1167-77, 2003 Nov.
Article En | MEDLINE | ID: mdl-14578855

The endogenous cannabinoid anandamide, a lipid mediator, induces various physiologic events such as vascular relaxation, inhibition of gap-junctions formation, tumor proliferation, neurologic analgesia, and apoptosis. Although increased concentration of anandamide in plasma has been implicated in pathophysiologic states including endotoxin-induced hypotension, the effects of anandamide on hepatocytes still remain unclear. In this study, we present evidence that plasma anandamide concentration is highly increased in severe hepatitis and cirrhosis patients. In addition, concentrations of anandamide within the pathophysiologic range potently induced apoptosis of hepatoma cell line (Hep G2) and primary hepatocytes, suggesting a possible link between increased anandamide level and hepatocyte damage. Anandamide-induced cell death was preceded by G0/G1 cell-cycle arrest, activation of proapoptotic signaling (i.e., p38 MAPK and JNK), and inhibition of antiapoptotic signaling (i.e., PKB/Akt) pathways. Moreover, anandamide increased susceptibility to oxidative stress-induced hepatocyte damage. In this context, methyl-beta-cyclodextrin (MCD), a membrane cholesterol depletor, or mevastatin, an HMG-CoA reductase inhibitor, or N-acetyl cysteine, an antioxidant, potently inhibited the anandamide-induced proapoptotic events and cell death, whereas putative cannabinoid receptor antagonists did not exhibit an inhibitory effect on anandamide-induced cell death. Furthermore, binding assay using polymyxin beads revealed that anandamide could interact with cholesterol. In conclusion, our data suggest that cholesterol present in the cell membrane determines the fate of hepatocytes exposed to anandamide, possibly functioning as an anandamide receptor.


Apoptosis/physiology , Arachidonic Acids/physiology , Cannabinoid Receptor Modulators/physiology , Cholesterol/physiology , Hepatocytes/physiology , Animals , Arachidonic Acids/blood , Cannabinoid Receptor Modulators/blood , Cell Membrane/metabolism , Cells, Cultured , Endocannabinoids , Female , Hepatitis/blood , Humans , Oxidative Stress/physiology , Polyunsaturated Alkamides , Rats , Rats, Wistar
14.
Thromb Haemost ; 89(5): 875-84, 2003 May.
Article En | MEDLINE | ID: mdl-12719786

Anandamide (AEA), an endogenous cannabinoid, is generated by macrophages during shock conditions, and is thought to be a causative mediator of septic shock. Thus, we hypothesized that AEA plays a crucial role in endothelial cell (EC) injury. Here, we demonstrate that AEA induces apoptosis in a time-and dose-dependent manner in human umbilical vein endothelial cells (HUVECs). AEA triggered phosphorylation of c-Jun NH(2)-terminal kinase (JNK) and p38 mitogen activated protein kinase. AEA also showed a marked increase of interleukin Ibeta- converting enzyme (ICE)CED-3 family protease (caspase-3) activity. AEA-induced EC death was inhibited by a selective vanilloid receptor 1 (VR1) antagonist, capsazepine, and was enhanced by a VR1 agonist, capsaicin, indicating that AEA induces apoptosis in ECs via VR1. In conclusion, we propose that AEA may play a crucial role in EC injury under conditions of shock, and that the use of inhibitors of the AEA regulation system may have a therapeutic effect under these conditions.


Apoptosis/drug effects , Arachidonic Acids/pharmacology , Endothelial Cells/drug effects , Caspase 3 , Caspases/metabolism , Cells, Cultured , Endocannabinoids , Endothelial Cells/pathology , Endothelium, Vascular/drug effects , Endothelium, Vascular/pathology , Humans , JNK Mitogen-Activated Protein Kinases , Kinetics , Mitogen-Activated Protein Kinases/metabolism , Phosphorylation/drug effects , Polyunsaturated Alkamides , Receptors, Drug/physiology , Shock, Septic/pathology , Umbilical Veins/cytology , p38 Mitogen-Activated Protein Kinases
15.
J Neurochem ; 87(6): 1345-53, 2003 Dec.
Article En | MEDLINE | ID: mdl-14713291

Ebselen, a selenium-containing heterocyclic compound, prevents ischemia-induced cell death. However, the molecular mechanism through which ebselen exerts its cytoprotective effect remains to be elucidated. Using sodium nitroprusside (SNP) as a nitric oxide (NO) donor, we show here that ebselen potently inhibits NO-induced apoptosis of differentiated PC12 cells. This was associated with inhibition of NO-induced phosphatidyl Serine exposure, cytochrome c release, and caspase-3 activation by ebselen. Analysis of key apoptotic regulators during NO-induced apoptosis of differentiated PC12 cells showed that ebselen blocks the activation of the apoptosis signaling-regulating kinase 1 (ASK1), and inhibits phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-jun N-terminal protein kinase (JNK). Moreover, ebselen inhibits NO-induced p53 phosphorylation at Ser15 and c-Jun phosphorylation at Ser63 and Ser73. It appears that inhibition of p38 MAPK and p53 phosphorylation by ebselen occurs via a thiol-redox-dependent mechanism. Interestingly, ebselen also activates p44/42 MAPK, and inhibits the downregulation of the antiapoptotic protein Bcl-2 in SNP-treated PC12 cells. Together, these findings suggest that ebselen protects neuronal cells from NO cytotoxicity by reciprocally regulating the apoptotic and antiapoptotic signaling cascades.


Apoptosis , Azoles/pharmacology , MAP Kinase Kinase Kinases/metabolism , Mitogen-Activated Protein Kinases/metabolism , Organoselenium Compounds/pharmacology , Proto-Oncogene Proteins c-bcl-2/metabolism , Tumor Suppressor Protein p53/metabolism , Animals , Annexin A5/metabolism , Blotting, Western , Butadienes/pharmacology , Caspase 3 , Caspases/metabolism , Cell Differentiation/drug effects , Cell Survival/drug effects , Chaperonin 60/metabolism , Cyclooxygenase Inhibitors/pharmacology , Cytochromes c/metabolism , Dithiothreitol/pharmacology , Dose-Response Relationship, Drug , Drug Interactions , Enzyme Activation/drug effects , Enzyme Inhibitors/pharmacology , In Vitro Techniques , Isoindoles , JNK Mitogen-Activated Protein Kinases , MAP Kinase Kinase Kinase 5 , Nerve Growth Factor/pharmacology , Nitric Oxide/metabolism , Nitric Oxide Donors/pharmacology , Nitriles/pharmacology , Nitroprusside/pharmacology , PC12 Cells , Propidium/metabolism , Rats , Serine/metabolism , Sodium Selenite/pharmacology , Time Factors , Transfection , Vitamin E/pharmacology , p38 Mitogen-Activated Protein Kinases
16.
Planta Med ; 68(1): 16-9, 2002 Jan.
Article En | MEDLINE | ID: mdl-11842320

The antioxidant effects of 1,5-anhydro-D-fructose (1,5-AF), a unique anhydrohexulose, were studied in 1,1-diphenyl-2-picrylhydrazyl (DPPH) solution, in human cells along with lipid peroxidation of low-density lipoprotein (LDL). We have confirmed that 1,5-AF scavenges DPPH radicals directly in solution and inhibits the formation of hydrogen peroxide and superoxide anion, typical reactive oxygen species (ROS), induced by phorbol myristate acetate (PMA) in a dose-dependent manner in THP-1 cells. We also observed the dose-dependent antioxidant effects of 1,5-AF on copper-mediated LDL oxidation. These findings suggest that 1,5-AF might play a role in reducing the risk of atherosclerosis and may help prevent coronary heart disease.


Antioxidants/pharmacology , Bepridil/analogs & derivatives , Carbohydrates/pharmacology , Free Radical Scavengers/pharmacology , Fructose/analogs & derivatives , Fructose/pharmacology , Picrates , Antioxidants/chemistry , Antioxidants/isolation & purification , Bepridil/administration & dosage , Bepridil/metabolism , Biological Factors , Biphenyl Compounds , Cell Line , Cells, Cultured , Dose-Response Relationship, Drug , Enzyme-Linked Immunosorbent Assay , Free Radical Scavengers/chemistry , Free Radical Scavengers/isolation & purification , Free Radicals/administration & dosage , Free Radicals/metabolism , Fructose/chemistry , Fructose/isolation & purification , Humans , Hydrogen Peroxide/metabolism , Hydroxyl Radical/metabolism , Lipid Peroxidation/drug effects , Lipoproteins, LDL/drug effects , Lipoproteins, LDL/metabolism , Macrophages , Molecular Structure , Monocytes/cytology , Monocytes/drug effects , Monocytes/metabolism , Reactive Oxygen Species/metabolism , Superoxides/metabolism , Tetradecanoylphorbol Acetate/administration & dosage
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