Acrolein-detoxifying isozymes of glutathione transferase in plants.

Science.gov (United States)

Mano, Jun'ichi; Ishibashi, Asami; Muneuchi, Hitoshi; Morita, Chihiro; Sakai, Hiroki; Biswas, Md Sanaullah; Koeduka, Takao; Kitajima, Sakihito

2017-02-01

Acrolein is a lipid-derived highly reactive aldehyde, mediating oxidative signal and damage in plants. We found acrolein-scavenging glutathione transferase activity in plants and purified a low K M isozyme from spinach. Various environmental stressors on plants cause the generation of acrolein, a highly toxic aldehyde produced from lipid peroxides, via the promotion of the formation of reactive oxygen species, which oxidize membrane lipids. In mammals, acrolein is scavenged by glutathione transferase (GST; EC 2.5.1.18) isozymes of Alpha, Pi, and Mu classes, but plants lack these GST classes. We detected the acrolein-scavenging GST activity in four species of plants, and purified an isozyme showing this activity from spinach (Spinacia oleracea L.) leaves. The isozyme (GST-Acr), obtained after an affinity chromatography and two ion exchange chromatography steps, showed the K M value for acrolein 93 μM, the smallest value known for acrolein-detoxifying enzymes in plants. Peptide sequence homology search revealed that GST-Acr belongs to the GST Tau, a plant-specific class. The Arabidopsis thaliana GST Tau19, which has the closest sequence similar to spinach GST-Acr, also showed a high catalytic efficiency for acrolein. These results suggest that GST plays as a scavenger for acrolein in plants.

Acrolein activates cell survival and apoptotic death responses involving the endoplasmic reticulum in A549 lung cells.

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Tanel, André; Pallepati, Pragathi; Bettaieb, Ahmed; Morin, Patrick; Averill-Bates, Diana A

2014-05-01

Acrolein, a highly reactive α,β-unsaturated aldehyde, is a product of endogenous lipid peroxidation. It is a ubiquitous environmental pollutant that is generated mainly by smoke, overheated cooking oil and vehicle exhaust. Acrolein damages cellular proteins, which could lead to accumulation of aberrantly-folded proteins in the endoplasmic reticulum (ER). This study determines the mechanisms involved in acrolein-induced apoptosis mediated by the ER and possible links with the ER stress response in human A549 lung cells. The exposure of cells to acrolein (15-50μM) for shorter times of 15 to 30min activated several ER stress markers. These included the ER chaperone protein BiP and the three ER sensors: (i) the survival/rescue molecules protein kinase RNA (PKR)-like ER kinase (PERK) and eukaryotic initiation factor 2 alpha (eIF2α) were phosphorylated; (ii) cleavage of activating transcription factor 6 (ATF6) occurred, and (iii) inositol-requiring protein-1 alpha (IRE1α) was phosphorylated. Acrolein (25-50μM) caused apoptotic cell death mediated by the ER after 2h, which was characterised by the induction of CHOP and activation of ER proteases calpain and caspase-4. Calpain and caspase-7 were the initiating factors for caspase-4 activation in acrolein-induced apoptosis. These results increase our knowledge about cellular responses to acrolein in lung cells, which have implications for human health. Copyright © 2014 Elsevier B.V. All rights reserved.

Dimercaprol is an acrolein scavenger that mitigates acrolein-mediated PC-12 cells toxicity and reduces acrolein in rat following spinal cord injury.

Science.gov (United States)

Tian, Ran; Shi, Riyi

2017-06-01

Acrolein is one of the most toxic byproducts of lipid peroxidation, and it has been shown to be associated with multiple pathological processes in trauma and diseases, including spinal cord injury, multiple sclerosis, and Alzheimer's disease. Therefore, suppressing acrolein using acrolein scavengers has been suggested as a novel strategy of neuroprotection. In an effort to identify effective acrolein scavengers, we have confirmed that dimercaprol, which possesses thiol functional groups, could bind and trap acrolein. We demonstrated the reaction between acrolein and dimercaprol in an abiotic condition by nuclear magnetic resonance spectroscopy. Specifically, dimercaprol is able to bind to both the carbon double bond and aldehyde group of acrolein. Its acrolein scavenging capability was further demonstrated by in vitro results that showed that dimercaprol could significantly protect PC-12 cells from acrolein-mediated cell death in a dose-dependent manner. Furthermore, dimercaprol, when applied systemically through intraperitoneal injection, could significantly reduce acrolein contents in spinal cord tissue following a spinal cord contusion injury in rats, a condition known to have elevated acrolein concentration. Taken together, dimercaprol may be an effective acrolein scavenger and a viable candidate for acrolein detoxification. © 2017 International Society for Neurochemistry.

Acrolein, an I-κBα-independent downregulator of NF-κB activity, causes the decrease in nitric oxide production in human malignant keratinocytes.

Science.gov (United States)

Moon, Ki-Young

2011-05-01

Acrolein, a reactive electrophilic α, β-unsaturated aldehyde, is known to be an alkylating chemical carcinogen. The effect of acrolein on the activation of NF-κB in human malignant epidermal keratinocytes was examined to elucidate the molecular mechanism associated with this NF-κB-acrolein regulation and its consecutive sequence, nitric oxide (NO) production. Acrolein significantly downregulated the cellular NF-κB activity up to 60% compared with control as well as the lipopolysaccharide (LPS)-induced NO production in a dose response manner at concentrations of 10~30 μM. To investigate the regulatory mechanism associated with this NF-κB-acrolein downregulation, the relative level of phosphorylation of I-κBα (serines-32 and -36), a principle regulator of NF-κB activation, represented by acrolein, was quantified. Acrolein inhibited NF-κB activity without altering cellular levels of the phosphorylated and nonphosphorylated forms of I-κBα, implying that the downregulatory effect of acrolein on cellular NF-κB activity in human skin cells is an I-κBα-independent activation pathway. The results suggests that acrolein causes the decrease in nitric oxide production as an I-κBα-independent downregulator of NF-κB activity in human malignant keratinocytes, and acrolein-induced carcinogenesis may be associated with the modulation of cellular NF-κB activity.

Acrolein Induces Endoplasmic Reticulum Stress and Causes Airspace Enlargement

Science.gov (United States)

Hanaoka, Masayuki; Natarajan, Ramesh; Kraskauskas, Donatas; Voelkel, Norbert F.

2012-01-01

Background Given the relative abundance and toxic potential of acrolein in inhaled cigarette smoke, it is surprising how little is known about the pulmonary and systemic effects of acrolein. Here we test the hypothesis whether systemic administration of acrolein could cause endoplasmic reticulum (ER) stress, and lung cell apoptosis, leading to the enlargement of the alveolar air spaces in rats. Methods Acute and chronic effects of intraperitoneally administered acrolein were tested. Mean alveolar airspace area was measured by using light microscopy and imaging system software. TUNEL staining and immunohistochemistry (IHC) for active caspase 3 and Western blot analysis for active caspase 3, and caspase 12 were performed to detect apoptosis. The ER-stress related gene expression in the lungs was determined by Quantitative real-time PCR analysis. Acrolein-protein adducts in the lung tissue were detected by IHC. Results Acute administration of acrolein caused a significant elevation of activated caspase 3, upregulation of VEGF expression and induced ER stress proteins in the lung tissue. The chronic administration of acrolein in rats led to emphysematous lung tissue remodeling. TUNEL staining and IHC for cleaved caspase 3 showed a large number of apoptotic septal cells in the acrolein-treated rat lungs. Chronic acrolein administration cause the endoplasmic reticulum stress response manifested by significant upregulation of ATF4, CHOP and GADd34 expression. In smokers with COPD there was a considerable accumulation of acrolein-protein adducts in the inflammatory, airway and vascular cells. Conclusions Systemic administration of acrolein causes endoplasmic reticulum stress response, lung cell apoptosis, and chronic administration leads to the enlargement of the alveolar air spaces and emphysema in rats. The substantial accumulation of acrolein-protein adducts in the lungs of COPD patients suggest a role of acrolein in the pathogenesis of emphysema. PMID:22675432

Upregulation of endothelial heme oxygenase-1 expression through the activation of the JNK pathway by sublethal concentrations of acrolein

International Nuclear Information System (INIS)

Wu, C.C.; Hsieh, C.W.; Lai, P.H.; Lin, J.B.; Liu, Y.C.; Wung, B.S.

2006-01-01

Acrolein is a highly electrophilic α,β-unsaturated aldehyde that is present in cigarette smoke. Heme oxygenase-1 (HO-1) is a cytoprotective enzyme activated by various such electrophilic compounds. In this study, the regulatory effects of acrolein upon the expression of HO-1 were investigated in endothelial cells (ECs). We demonstrate that acrolein induces the elevation of HO-1 protein levels, and subsequent enzyme activity, at non-cytotoxic concentrations. An additional α,β-unsaturated aldehyde, cinnamaldehyde, was also found to increase HO-1 expression and have less cytotoxicity than acrolein. Moreover, acrolein-mediated HO-1 induction is abrogated in the presence of actinomycin D and cycloheximide. Nrf2 is a transcription factor involved in the induction of HO-1 through an antioxidant response element (ARE) in the promoter region of the HO-1 gene. We show that acrolein induces Nrf2 translocation and ARE-luciferase reporter activity. Acrolein was also found to induce the production of both superoxide and H 2 O 2 at levels greater than 100 μM. However, with the exception of NAC, no antioxidant generated any effect upon acrolein-dependent HO-1 expression in ECs. Our present findings suggest that reactive oxygen species (ROS) may not be a major modulator for HO-1 induction. Using buthionine sulfoximine to deplete the intracellular GSH levels further enhanced the effects of acrolein. We also found that cellular GSH level was rapidly reduced after both 10 and 100 μM acrolein treatment. However, after 6 h of exposure to ECs, only 10 μM acrolein treatment increases GSH level. In addition, only the JNK inhibitor SP600125 and tyrosine kinase inhibitor genistein had any significant inhibitory impact upon the upregulation of HO-1 by acrolein. Pretreatment with a range of other PI3 kinase inhibitors, including wortmannin and LY294002, showed no effects. Hence, we show in our current experiments that a sublethal concentration of acrolein is in fact a novel HO-1 inducer

Upregulation of endothelial heme oxygenase-1 expression through the activation of the JNK pathway by sublethal concentrations of acrolein.

Science.gov (United States)

Wu, C C; Hsieh, C W; Lai, P H; Lin, J B; Liu, Y C; Wung, B S

2006-08-01

Acrolein is a highly electrophilic alpha,beta-unsaturated aldehyde that is present in cigarette smoke. Heme oxygenase-1 (HO-1) is a cytoprotective enzyme activated by various such electrophilic compounds. In this study, the regulatory effects of acrolein upon the expression of HO-1 were investigated in endothelial cells (ECs). We demonstrate that acrolein induces the elevation of HO-1 protein levels, and subsequent enzyme activity, at non-cytotoxic concentrations. An additional alpha,beta-unsaturated aldehyde, cinnamaldehyde, was also found to increase HO-1 expression and have less cytotoxicity than acrolein. Moreover, acrolein-mediated HO-1 induction is abrogated in the presence of actinomycin D and cycloheximide. Nrf2 is a transcription factor involved in the induction of HO-1 through an antioxidant response element (ARE) in the promoter region of the HO-1 gene. We show that acrolein induces Nrf2 translocation and ARE-luciferase reporter activity. Acrolein was also found to induce the production of both superoxide and H2O2 at levels greater than 100 microM. However, with the exception of NAC, no antioxidant generated any effect upon acrolein-dependent HO-1 expression in ECs. Our present findings suggest that reactive oxygen species (ROS) may not be a major modulator for HO-1 induction. Using buthionine sulfoximine to deplete the intracellular GSH levels further enhanced the effects of acrolein. We also found that cellular GSH level was rapidly reduced after both 10 and 100 microM acrolein treatment. However, after 6 h of exposure to ECs, only 10 microM acrolein treatment increases GSH level. In addition, only the JNK inhibitor SP600125 and tyrosine kinase inhibitor genistein had any significant inhibitory impact upon the upregulation of HO-1 by acrolein. Pretreatment with a range of other PI3 kinase inhibitors, including wortmannin and LY294002, showed no effects. Hence, we show in our current experiments that a sublethal concentration of acrolein is in fact a

Acrolein health effects.

Science.gov (United States)

Faroon, O; Roney, N; Taylor, J; Ashizawa, A; Lumpkin, M H; Plewak, D J

2008-08-01

Acrolein is a chemical used as an intermediate reactive aldehyde in chemical industry. It is used for synthesis of many organic substances, methionine production, and methyl chloride refrigerant. The general population is exposed to acrolein via smoking, second-hand smoke, exposure to wood and plastic smoke. Firefighters and population living or working in areas with heavy automotive traffic may expose to higher level of acrolein via inhalation of smoke or automotive exhaust. Degradation of acrolein in all environmental media occurs rapidly, therefore, environmental accumulation is not expected. Acrolein degrade in 6A days when applied to surface water, and it has not been found as a contaminant in municipal drinking water. Acrolein vapor may cause eye, nasal and respiratory tract irritations in low level exposure. A decrease in breathing rate was reported by volunteers acutely exposed to 0.3A ppm of acrolein. At similar level, mild nasal epithelial dysplasia, necrosis, and focal basal cell metaplasia have been observed in rats. The acrolein effects on gastrointestinal mucosa in the animals include epithelial hyperplasia, ulceration, and hemorrhage. The severity of the effects is dose dependent. Acrolein induces the respiratory, ocular, and gastrointestinal irritations by inducing the release of peptides in nerve terminals innervating these systems. Levels of acrolein between 22 and 249 ppm for 10 min induced a dose-related decrease in substance P (a short-chain polypeptide that functions as a neurotransmitter or neuromodulator).

Effects of acrolein on leukotriene biosynthesis in human neutrophils.

Science.gov (United States)

Berry, Karin A Zemski; Henson, Peter M; Murphy, Robert C

2008-12-01

Acrolein is a toxic, highly reactive alpha,beta-unsaturated aldehyde that is present in high concentrations in cigarette smoke. In the current study, the effect of acrolein on eicosanoid synthesis in stimulated human neutrophils was examined. Eicosanoid synthesis in neutrophils was initiated by priming with granulocyte-macrophage colony-stimulating factor (GM-CSF) and subsequent stimulation with formyl-methionyl-leucyl-phenylalanine (fMLP) and 5-lipoxygenase (5-LO) products in addition to small amounts of cyclooxygenase (COX) products were detected using LC/MS/MS. A dose-dependent decrease in the formation of 5-LO products was observed in GM-CSF/fMLP-stimulated neutrophils when acrolein (0-50 microM) was present with almost complete inhibition at > or = 25 microM acrolein. The production of COX products was not affected by acrolein in these cells. The effect of acrolein was examined on key parts of the eicosanoid pathway, such as arachidonic acid release, intracellular calcium ion concentration, and adenosine production. In addition, the direct effect of acrolein on 5-LO enzymatic activity was probed using a recombinant enzyme. Some of these factors were affected by acrolein but did not completely explain the almost complete inhibition of 5-LO product formation in GM-CSF/fMLP-treated cells with acrolein. In addition, the effect of acrolein on different stimuli that initiate the 5-LO pathway [platelet-activating factor (PAF)/fMLP, GM-CSF/PAF, opsonized zymosan, and A23187] was examined. Acrolein had no significant effect on the leukotriene production in neutrophils stimulated with PAF/fMLP, GM-CSF/ PAF, or OPZ. Additionally, 50% inhibition of the 5-LO pathway was observed in A23187-stimulated neutrophils. Our results suggest that acrolein has a profound effect on the 5-LO pathway in neutrophils, which may have implications in disease states, such as chronic obstructive pulmonary disease and other pulmonary disease, where both activated neutrophils and acrolein are

p38 MAPK and MMP-9 cooperatively regulate mucus overproduction in mice exposed to acrolein fog.

Science.gov (United States)

Liu, Dai-Shun; Wang, Tao; Han, Su-Xia; Dong, Jia-Jia; Liao, Zeng-Lin; He, Guang-Ming; Chen, Lei; Chen, Ya-Juan; Xu, Dan; Hou, Yan; Li, Yan-Ping; Wen, Fu-Qiang

2009-09-01

To evaluate the role of p38 mitogen-activated protein kinase (MAPK) on mice airway inflammation, mucus production and the possible cross-talk between p38 MAPK and matrix metalloproteinase-9 (MMP-9) in mucin protein synthesis. Mice were exposed to 4.0 ppm of acrolein for 21 days with daily intraperitoneal injection of SB203580, a specific inhibitor of p38 MAPK. In control mice, sterile saline was administered instead. On days 7 and 21, mice were sacrificed to examine airway inflammation and mucus production by BALF cell counts, cytokine ELISA, and H&E and AB-PAS staining. The mRNA and protein levels of Muc5ac, p38 MAPK and MMP-9 in the lung were determined by RT-PCR, immunohistochemistry and Western blotting analysis. MMP-9 activity was measured by gelatin zymography. Both the numbers of inflammatory cells and mucus-secreting goblet cells were significantly increased in the airways of mice exposed to acrolein as compared to the control mice. Acrolein-increased phosphorylation of p38 MAPK was significantly reduced by SB203580. The airway inflammation and goblet cell hyperplasia after acrolein challenge were also attenuated by SB203580 administration. Moreover, SB203580 treatment decreased the acrolein-induced increase of Muc5ac and MMP-9 expression and MMP-9 activity in airway epithelium. The results indicate an important role of p38 MAPK in acrolein-induced airway inflammation and mucus hypersecretion in mice. The cooperation of p38 and MMP-9 may contribute to the mucin overproduction after inflammatory challenge.

Acrolein stimulates eicosanoid release from bovine airway epithelial cells

International Nuclear Information System (INIS)

Doupnik, C.A.; Leikauf, G.D.

1990-01-01

Injury to the airway mucosa after exposure to environmental irritants is associated with pulmonary inflammation and bronchial hyperresponsiveness. To better understand the relationships between mediator release and airway epithelial cell injury during irritant exposures, we studied the effects of acrolein, a low-molecular-weight aldehyde found in cigarette smoke, on arachidonic acid metabolism in cultured bovine tracheal epithelial cells. Confluent airway epithelial cell monolayers, prelabeled with [3H]arachidonic acid, released significant levels of 3H activity when exposed (20 min) to 100 microM acrolein. [3H]arachidonic acid products were resolved using reverse-phase high-performance liquid chromatography. Under control conditions the released 3H activity coeluted predominantly with the cyclooxygenase product, prostaglandin (PG) E2. After exposure to acrolein, significant peaks in 3H activity coeluted with the lipoxygenase products 12-hydroxyeicosatetraenoic acid (HETE) and 15-HETE, as well as with PGE2, PGF2 alpha, and 6-keto-PGF1 alpha. Dose-response relationships for acrolein-induced release of immunoreactive PGF2 alpha and PGE2 from unlabeled epithelial monolayers demonstrated 30 microM acrolein as the threshold dose, with 100 microM acrolein inducing nearly a fivefold increase in both PGF2 alpha and PGE2. Cellular viability after exposure to 100 microM acrolein, determined by released lactate dehydrogenase activity, was not affected until exposure periods were greater than or equal to 2 h. These results implicate the airway epithelial cell as a possible source of eicosanoids after exposure to acrolein

Acrolein cytotoxicity in hepatocytes involves endoplasmic reticulum stress, mitochondrial dysfunction and oxidative stress

International Nuclear Information System (INIS)

Mohammad, Mohammad K.; Avila, Diana; Zhang, Jingwen; Barve, Shirish; Arteel, Gavin; McClain, Craig; Joshi-Barve, Swati

2012-01-01

Acrolein is a common environmental, food and water pollutant and a major component of cigarette smoke. Also, it is produced endogenously via lipid peroxidation and cellular metabolism of certain amino acids and drugs. Acrolein is cytotoxic to many cell types including hepatocytes; however the mechanisms are not fully understood. We examined the molecular mechanisms underlying acrolein hepatotoxicity in primary human hepatocytes and hepatoma cells. Acrolein, at pathophysiological concentrations, caused a dose-dependent loss of viability of hepatocytes. The death was apoptotic at moderate and necrotic at high concentrations of acrolein. Acrolein exposure rapidly and dramatically decreased intracellular glutathione and overall antioxidant capacity, and activated the stress-signaling MAP-kinases JNK, p42/44 and p38. Our data demonstrate for the first time in human hepatocytes, that acrolein triggered endoplasmic reticulum (ER) stress and activated eIF2α, ATF-3 and -4, and Gadd153/CHOP, resulting in cell death. Notably, the protective/adaptive component of ER stress was not activated, and acrolein failed to up-regulate the protective ER-chaperones, GRP78 and GRP94. Additionally, exposure to acrolein disrupted mitochondrial integrity/function, and led to the release of pro-apoptotic proteins and ATP depletion. Acrolein-induced cell death was attenuated by N-acetyl cysteine, phenyl-butyric acid, and caspase and JNK inhibitors. Our data demonstrate that exposure to acrolein induces a variety of stress responses in hepatocytes, including GSH depletion, oxidative stress, mitochondrial dysfunction and ER stress (without ER-protective responses) which together contribute to acrolein toxicity. Our study defines basic mechanisms underlying liver injury caused by reactive aldehyde pollutants such as acrolein. -- Highlights: ► Human primary hepatocytes and cultured cell lines are used. ► Multiple cell death signaling pathways are activated by acrolein. ► Novel finding of

Acrolein cytotoxicity in hepatocytes involves endoplasmic reticulum stress, mitochondrial dysfunction and oxidative stress

Energy Technology Data Exchange (ETDEWEB)

Mohammad, Mohammad K. [Department of Medicine, University of Louisville (United States); Alcohol Research Center, University of Louisville (United States); Avila, Diana [Department of Medicine, University of Louisville (United States); Department of Pharmacology and Toxicology, University of Louisville (United States); Alcohol Research Center, University of Louisville (United States); Zhang, Jingwen [Department of Medicine, University of Louisville (United States); Alcohol Research Center, University of Louisville (United States); Barve, Shirish [Department of Medicine, University of Louisville (United States); Department of Pharmacology and Toxicology, University of Louisville (United States); Alcohol Research Center, University of Louisville (United States); Arteel, Gavin [Department of Pharmacology and Toxicology, University of Louisville (United States); Alcohol Research Center, University of Louisville (United States); McClain, Craig [Department of Medicine, University of Louisville (United States); Department of Pharmacology and Toxicology, University of Louisville (United States); Alcohol Research Center, University of Louisville (United States); Robley Rex VAMC, Louisville, KY (United States); Joshi-Barve, Swati, E-mail: s0josh01@louisville.edu [Department of Medicine, University of Louisville (United States); Department of Pharmacology and Toxicology, University of Louisville (United States); Alcohol Research Center, University of Louisville (United States)

2012-11-15

Acrolein is a common environmental, food and water pollutant and a major component of cigarette smoke. Also, it is produced endogenously via lipid peroxidation and cellular metabolism of certain amino acids and drugs. Acrolein is cytotoxic to many cell types including hepatocytes; however the mechanisms are not fully understood. We examined the molecular mechanisms underlying acrolein hepatotoxicity in primary human hepatocytes and hepatoma cells. Acrolein, at pathophysiological concentrations, caused a dose-dependent loss of viability of hepatocytes. The death was apoptotic at moderate and necrotic at high concentrations of acrolein. Acrolein exposure rapidly and dramatically decreased intracellular glutathione and overall antioxidant capacity, and activated the stress-signaling MAP-kinases JNK, p42/44 and p38. Our data demonstrate for the first time in human hepatocytes, that acrolein triggered endoplasmic reticulum (ER) stress and activated eIF2α, ATF-3 and -4, and Gadd153/CHOP, resulting in cell death. Notably, the protective/adaptive component of ER stress was not activated, and acrolein failed to up-regulate the protective ER-chaperones, GRP78 and GRP94. Additionally, exposure to acrolein disrupted mitochondrial integrity/function, and led to the release of pro-apoptotic proteins and ATP depletion. Acrolein-induced cell death was attenuated by N-acetyl cysteine, phenyl-butyric acid, and caspase and JNK inhibitors. Our data demonstrate that exposure to acrolein induces a variety of stress responses in hepatocytes, including GSH depletion, oxidative stress, mitochondrial dysfunction and ER stress (without ER-protective responses) which together contribute to acrolein toxicity. Our study defines basic mechanisms underlying liver injury caused by reactive aldehyde pollutants such as acrolein. -- Highlights: ► Human primary hepatocytes and cultured cell lines are used. ► Multiple cell death signaling pathways are activated by acrolein. ► Novel finding of

ROLE OF ENDOPLASMIC RETICULUM STRESS IN ACROLEIN-INDUCED ENDOTHELIAL ACTIVATION

OpenAIRE

Haberzettl, Petra; Vladykovskaya, Elena; Srivastava, Sanjay; Bhatnagar, Aruni

2008-01-01

Acrolein is a ubiquitous environmental pollutant and an endogenous product of lipid peroxidation. It is also generated during the metabolism of several drugs and amino acids. In this study, we examined the effects of acrolein on endothelial cells. Treatment of human umbilical vein endothelial cells (HUVECs) with 2 to 10 μM acrolein led to an increase in the phosphorylation of eIF-2α within 10 to 30 min of exposure. This was followed by alternate splicing of XBP-1 mRNA and an increase in the e...

Effect of acrolein and glutathione depleting agents on thioredoxin

International Nuclear Information System (INIS)

Yang Xianmei; Wu Xuli; Choi, Young Eun; Kern, Julie C.; Kehrer, James P.

2004-01-01

Acrolein is a widespread environmental pollutant that reacts rapidly with nucleophiles, especially cellular thiols. In addition to glutathione (GSH), thioredoxin (Trx) and thioredoxin reductase (TR) contain thiol groups and may react with electrophiles. In the present study, A549 cells treated with 5-25 μM acrolein for 30 min lost cellular Trx activity in a dose-dependent fashion. Over 90% of Trx activity was lost at concentrations of 25 μM or greater. In contrast, Trx protein content, as assessed by western blotting, was not altered immediately after the 30 min acrolein treatment. Both Trx activity and protein levels increased 4 h after the acrolein treatment. However, Trx activity remained below control levels at 24 h. A similar dose-response relationship was seen with TR in A549 cells exposed to acrolein. There was, however, a rapid recovery of TR activity such that it attained normal levels by 4 h after doses ≤75 μM acrolein. Diethyl maleate (DEM), a common but not highly specific, agent used to deplete GSH, also inactivated Trx. A 2 h exposure of A549 cells to 1 mM DEM depleted cellular GSH by ∼50% and diminished Trx activity by over 67%. Lower DEM doses (0.125 mM and 0.25 mM) for 1 h had no significant effect on GSH but significantly decreased Trx activity 12 and 23%, respectively. Similar to immediately after acrolein exposure, DEM did not affect Trx protein levels. A Trx-1-GFP fusion protein was transfected into A549 cells. While the fusion protein was expressed, the Trx component was inactive by the insulin reducing assay. In summary, Trx and TR are inactivated by acrolein. In addition, the GSH depleting agent DEM inactivates Trx somewhat more effectively than it depletes GSH. The Trx-1-GFP fusion protein, while readily expressed, appears to have little or no activity, perhaps because the small size of Trx-1 (12 kDa) is affected by the larger GFP

Acrolein exposure suppresses antigen-induced pulmonary inflammation

Science.gov (United States)

2013-01-01

Background Adverse health effects of tobacco smoke arise partly from its influence on innate and adaptive immune responses, leading to impaired innate immunity and host defense. The impact of smoking on allergic asthma remains unclear, with various reports demonstrating that cigarette smoke enhances asthma development but can also suppress allergic airway inflammation. Based on our previous findings that immunosuppressive effects of smoking may be largely attributed to one of its main reactive electrophiles, acrolein, we explored the impact of acrolein exposure in a mouse model of ovalbumin (OVA)-induced allergic asthma. Methods C57BL/6 mice were sensitized to ovalbumin (OVA) by intraperitoneal injection with the adjuvant aluminum hydroxide on days 0 and 7, and challenged with aerosolized OVA on days 14–16. In some cases, mice were also exposed to 5 ppm acrolein vapor for 6 hrs/day on days 14–17. Lung tissues or brochoalveolar lavage fluids (BALF) were collected either 6 hrs after a single initial OVA challenge and/or acrolein exposure on day 14 or 48 hrs after the last OVA challenge, on day 18. Inflammatory cells and Th1/Th2 cytokine levels were measured in BALF, and lung tissue samples were collected for analysis of mucus and Th1/Th2 cytokine expression, determination of protein alkylation, cellular thiol status and transcription factor activity. Results Exposure to acrolein following OVA challenge of OVA-sensitized mice resulted in markedly attenuated allergic airway inflammation, demonstrated by decreased inflammatory cell infiltrates, mucus hyperplasia and Th2 cytokines. Acrolein exposure rapidly depleted lung tissue glutathione (GSH) levels, and induced activation of the Nrf2 pathway, indicated by accumulation of Nrf2, increased alkylation of Keap1, and induction of Nrf2-target genes such as HO-1. Additionally, analysis of inflammatory signaling pathways showed suppressed activation of NF-κB and marginally reduced activation of JNK in acrolein

Acrolein induced both pulmonary inflammation and the death of lung epithelial cells.

Science.gov (United States)

Sun, Yang; Ito, Sachiko; Nishio, Naomi; Tanaka, Yuriko; Chen, Nana; Isobe, Ken-Ichi

2014-09-02

Acrolein, a compound found in cigarette smoke, is a major risk factor for respiratory diseases. Previous research determined that both acrolein and cigarette smoke produced reactive oxygen species (ROS). As many types of pulmonary injuries are associated with inflammation, this study sought to ascertain the extent to which exposure to acrolein advanced inflammatory state in the lungs. Our results showed that intranasal exposure of mice to acrolein increased CD11c(+)F4/80(high) macrophages in the lungs and increased ROS formation via induction of NF-κB signaling. Treatment with acrolein activated macrophages and led to their increased production of ROS and expression of several key pro-inflammatory cytokines. In in vitro studies, acrolein treatment of bone marrow-derived GM-CSF-dependent immature macrophages (GM-IMs), activated the cells and led to their increased production of ROS and expression of several key pro-inflammatory cytokines. Acrolein treatment of macrophages induced apoptosis of lung epithelial cells. Inclusion of an inhibitor of ROS formation markedly decreased acrolein-mediated macrophage activation and reduced the extent of epithelial cell death. These results indicate that acrolein can cause lung damage, in great part by mediating the increased release of pro-inflammatory cytokines/factors by macrophages. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Alda-1 Protects Against Acrolein-Induced Acute Lung Injury and Endothelial Barrier Dysfunction.

Science.gov (United States)

Lu, Qing; Mundy, Miles; Chambers, Eboni; Lange, Thilo; Newton, Julie; Borgas, Diana; Yao, Hongwei; Choudhary, Gaurav; Basak, Rajshekhar; Oldham, Mahogany; Rounds, Sharon

2017-12-01

Inhalation of acrolein, a highly reactive aldehyde, causes lung edema. The underlying mechanism is poorly understood and there is no effective treatment. In this study, we demonstrated that acrolein not only dose-dependently induced lung edema but also promoted LPS-induced acute lung injury. Importantly, acrolein-induced lung injury was prevented and rescued by Alda-1, an activator of mitochondrial aldehyde dehydrogenase 2. Acrolein also dose-dependently increased monolayer permeability, disrupted adherens junctions and focal adhesion complexes, and caused intercellular gap formation in primary cultured lung microvascular endothelial cells (LMVECs). These effects were attenuated by Alda-1 and the antioxidant N-acetylcysteine, but not by the NADPH inhibitor apocynin. Furthermore, acrolein inhibited AMP-activated protein kinase (AMPK) and increased mitochondrial reactive oxygen species levels in LMVECs-effects that were associated with impaired mitochondrial respiration. AMPK total protein levels were also reduced in lung tissue of mice and LMVECs exposed to acrolein. Activation of AMPK with 5-aminoimidazole-4-carboxamide-1-β-4-ribofuranoside blunted an acrolein-induced increase in endothelial monolayer permeability, but not mitochondrial oxidative stress or inhibition of mitochondrial respiration. Our results suggest that acrolein-induced mitochondrial dysfunction may not contribute to endothelial barrier dysfunction. We speculate that detoxification of acrolein by Alda-1 and activation of AMPK may be novel approaches to prevent and treat acrolein-associated acute lung injury, which may occur after smoke inhalation.

Doxycycline attenuates acrolein-induced mucin production, in part by inhibiting MMP-9.

Science.gov (United States)

Ren, Shuang; Guo, Ling-Li; Yang, Jie; Liu, Dai-Shun; Wang, Tao; Chen, Lei; Chen, Ya-Juan; Xu, Dan; Feng, Yu-Lin; Wen, Fu-Qiang

2011-01-10

Matrix metalloproteinases (MMPs), especially MMP-9, have been found to increase the expression of epidermal growth factor (EGF) receptor, a possible regulator of acrolein-induced mucin expression in the airway epithelium. The aim of this study was to investigate whether doxycycline, a tetracycline antibiotic that inhibits MMPs, attenuates mucus production and synthesis of mucin MUC5AC in acrolein-exposed rats. Sprague-Dawley rats were exposed to acrolein aerosol [3.0parts/million (ppm), 6h/day, 12days] and they received 20mg/kg doxycycline daily by gavage, beginning two days before exposure to acrolein until the end of the experiment. The production of mucin glycoproteins and expression of the MMP-9 and MUC5AC genes were measured in rat trachea. The increase in levels of MMP-9 mRNA and protein in airway epithelium after acrolein exposure was accompanied by an increase in MUC5AC mRNA expression. Doxycycline significantly prevented these increases in acrolein-induced expression of MMP-9 and MUC5AC and attenuated mucus production in tracheal epithelium. These results indicate that doxycycline attenuated acrolein-induced mucin synthesis, in part by inhibiting expression of MMP-9. Thus doxycycline may have a prophylactic effect in the treatment of smoking-induced mucus hypersecretion. Crown Copyright © 2010. Published by Elsevier B.V. All rights reserved.

Synthesis of Reactive Polymers for Acrolein Capture Using AGET ATRP.

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Beringer, Laura T; Li, Shaohua; Gilmore, Gary; Lister, John; Averick, Saadyah

2015-10-05

Acrolein is a toxic metabolite of the anticancer agent cyclophosphamide (CP). Current strategies to mitigate acrolein toxicity are insufficient, and in this brief article, we report the synthesis of well-defined low molecular weight block copolymers using activators generated by electron transfer atom transfer radical polymerization (AGET ATRP) capable of reacting with the cytotoxic small molecule acrolein. Acrolein reactivity was introduced into the block copolymers via incorporation of either (a) aminooxy or (b) sulfhydryl groups. The cytoprotective effect of the polymers was compared to sodium 2-sulfanylethanesulfonate (mesna) the current gold standard for protection from CP urotoxicity, and we found that the polymers bearing sulfhydryl moieties demonstrated superior cytoprotective activity.

Effects of acrolein on the production of corticosterone in male rats.

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Yeh, Yung-Hsing; Chou, Jou-Chun; Weng, Ting-Chun; Lieu, Fu-Kong; Lin, Jou-Yu; Yeh, Chii-Chang; Hu, Sindy; Wang, Paulus S; Idova, Galina; Wang, Shyi-Wu

2016-07-01

Acrolein, an α, β-unsaturated aldehyde, exists in a wide range of sources. Acrolein can be not only generated from all types of smoke but also produced endogenously from the metabolism by lipid peroxidation. The cellular influence of acrolein is due to its electrophilic character via binding to and depleting cellular nucleophiles. Although the toxicity of acrolein has been extensively studied, there is relatively little information about its impact on hormone release. This study aimed at the effect of acrolein on hypothalamic-pituitary-adrenal (H-P-A) axis. In an in vivo study, male rats were administrated with acrolein for 1 or 3days. The plasma corticosterone in response to a single injection of adrenocorticotropic hormone (ACTH) increased slowly in acrolein-pretreated rats than in control rats. Further investigating the steroidogenic pathway, the protein expressions of steroidogenic acute regulatory protein (StAR) and the upper receptor-melanocortin 2 receptor (MC2R) were attenuated in acrolein-treated groups. Another experiment using trilostane showed less activity of P450scc in zona fasciculata-reticularis (ZFR) cells in acrolein-treated groups. In addition to the suppressed ability of corticosterone production in ZFR cells, acrolein even had extended influence at higher concentrations. The lower ACTH was observed in the plasma from acrolein-pretreated rats. In an in vitro study, ZFR cells were incubated with acrolein and the results showed that corticosterone concentrations in media were decreased in a dose-dependent manner. Acrolein also desensitized the response of the ZFR cells to ACTH. These results suggested that acrolein decreased the releasing ability of corticosterone via an inhibition on the response of ZFR cells to ACTH and the reduction of protein expressions of StAR and MC2R as well as the activity of P450scc in rat ZFR cells. The present evidences showed that the H-P-A axis was affected by the administration of acrolein. Copyright © 2016

Acrolein cytotoxicity in hepatocytes involves endoplasmic reticulum stress, mitochondrial dysfunction and oxidative stress

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Mohammad, Mohammad K; Avila, Diana; Zhang, Jingwen; Barve, Shirish; Arteel, Gavin; McClain, Craig; Joshi-Barve, Swati

2012-01-01

Acrolein is a common environmental, food and water pollutant and a major component of cigarette smoke. Also, it is produced endogenously via lipid peroxidation and cellular metabolism of certain amino acids and drugs. Acrolein is cytotoxic to many cell types including hepatocytes; however the mechanisms are not fully understood. We examined the molecular mechanisms underlying acrolein hepatotoxicity in primary human hepatocytes and hepatoma cells. Acrolein, at pathophysiological concentrations, caused a dose-dependent loss of viability of hepatocytes. The death was apoptotic at moderate and necrotic at high concentrations of acrolein. Acrolein exposure rapidly and dramatically decreased intracellular glutathione and overall antioxidant capacity, and activated the stress-signaling MAP-kinases JNK, p42/44 and p38. Our data demonstrate for the first time in human hepatocytes, that acrolein triggered endoplasmic reticulum (ER) stress and activated eIF2α, ATF-3 and -4, and Gadd153/CHOP, resulting in cell death. Notably, the protective/adaptive component of ER stress was not activated, and acrolein failed to up-regulate the protective ER-chaperones, GRP78 and GRP94. Additionally, exposure to acrolein disrupted mitochondrial integrity/function, and led to the release of pro-apoptotic proteins and ATP depletion. Acrolein-induced cell death was attenuated by N-acetyl cysteine, phenyl-butyric acid, and caspase and JNK inhibitors. Our data demonstrate that exposure to acrolein induces a variety of stress responses in hepatocytes, including GSH depletion, oxidative stress, mitochondrial dysfunction and ER stress (without ER-protective responses) which together contribute to acrolein toxicity. Our study defines basic mechanisms underlying liver injury caused by reactive aldehyde pollutants such as acrolein. PMID:23026831

Aldose reductase regulates acrolein-induced cytotoxicity in human small airway epithelial cells.

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Yadav, Umesh C S; Ramana, K V; Srivastava, Satish K

2013-12-01

Aldose reductase (AR), a glucose-metabolizing enzyme, reduces lipid aldehydes and their glutathione conjugates with more than 1000-fold efficiency (Km aldehydes 5-30 µM) relative to glucose. Acrolein, a major endogenous lipid peroxidation product as well as a component of environmental pollutants and cigarette smoke, is known to be involved in various pathologies including atherosclerosis, airway inflammation, COPD, and age-related disorders, but the mechanism of acrolein-induced cytotoxicity is not clearly understood. We have investigated the role of AR in acrolein-induced cytotoxicity in primary human small airway epithelial cells (SAECs). Exposure of SAECs to varying concentrations of acrolein caused cell death in a concentration- and time-dependent manner. AR inhibition by fidarestat prevented the low-dose (5-10 µM) but not the high-dose (>10 µM) acrolein-induced SAEC death. AR inhibition protected SAECs from low-dose (5 µM) acrolein-induced cellular reactive oxygen species (ROS). Inhibition of acrolein-induced apoptosis by fidarestat was confirmed by decreased condensation of nuclear chromatin, DNA fragmentation, comet tail moment, and annexin V fluorescence. Further, fidarestat inhibited acrolein-induced translocation of the proapoptotic proteins Bax and Bad from the cytosol to the mitochondria and that of Bcl2 and BclXL from the mitochondria to the cytosol. Acrolein-induced cytochrome c release from mitochondria was also prevented by AR inhibition. The mitogen-activated protein kinases (MAPKs), such as extracellular signal-regulated kinases 1 and 2, stress-activated protein kinase/c-Jun NH2-terminal kinase, and p38MAPK, and c-Jun were transiently activated in airway epithelial cells by acrolein in a concentration- and time-dependent fashion, which was significantly prevented by AR inhibition. These results suggest that AR inhibitors could prevent acrolein-induced cytotoxicity in the lung epithelial cells. Copyright © 2013 Elsevier Inc. All rights

Aldose reductase regulates acrolein-induced cytotoxicity in human small airway epithelial cells

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Yadav, Umesh CS; Ramana, KV; Srivastava, SK

2013-01-01

Aldose reductase (AR), a glucose metabolizing enzyme, reduces lipid aldehydes and their glutathione conjugates with more than 1000-fold efficiency (Km aldehydes 5-30μM) than glucose. Acrolein, a major endogenous lipid peroxidation product as well as component of environmental pollutant and cigarette smoke, is known to be involved in various pathologies including atherosclerosis, airway inflammation, COPD, and age-related disorders but the mechanism of acrolein-induced cytotoxicity is not clearly understood. We have investigated the role of AR in acrolein-induced cytotoxicity in primary human small airway epithelial cells SAECs. Exposure of SAECs to varying concentrations of acrolein caused cell-death in a concentration- and time-dependent manner. AR inhibition by fidarestat prevented the low (5 to 10 μM) but not high (>10 μM) concentrations of acrolein-induced SAECs cell death. AR inhibition protected SAECs from low dose (5 μM) acrolein-induced cellular reactive oxygen species (ROS). Inhibition of acrolein-induced apoptosis by fidarestat was confirmed by decreased condensation of nuclear chromatin, DNA fragmentation, comet tail-moment, and annexin-V fluorescence. Further, fidarestat inhibited acrolein-induced translocation of pro-apoptotic proteins Bax and Bad from cytosol to the mitochondria, and that of Bcl2 and BclXL from mitochondria to cytosol. Acrolein-induced cytochrome c release from mitochondria was also prevented by AR inhibition. The mitogen-activated protein kinases (MAPK) such as extracellular signal-regulated kinases 1 and 2 (ERK1/2), stress-activated protein kinases/c-jun NH2-terminal kinases (SAPK/JNK) and p38MAPK, and c-jun were transiently activated in airway epithelial cells by acrolein in a concentration and time-dependent fashion, which were significantly prevented by AR inhibition. These results suggest that AR inhibitors could prevent acrolein-induced cytotoxicity in the lung epithelial cells. PMID:23770200

Exogenous Acrolein intensifies sensory hypersensitivity after spinal cord injury in rat.

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Butler, Breanne; Acosta, Glen; Shi, Riyi

2017-08-15

Acrolein, an α,β-unsaturated aldehyde associated with oxidative stress, is also a major toxic component of tobacco cigarette smoke, which has been reported in the clinic to coincide with the exacerbation of neuropathic pain after SCI. Previous reports have shown that acrolein involvement in spinal cord injury (SCI) is crucial to the development and persistence of neuropathic pain. Through the activation and upregulation of the transient receptor protein ankyrin-1 (TRPA1) cation channel, acrolein is capable of sensitizing the central nervous system in the acute and chronic stages of SCI. Here, we report that the acute or delayed nasal exposure of acrolein, apart from cigarette smoke but at concentrations similar to that found in cigarette smoke, resulted in increased neuropathic pain behaviors in a rat model of contusion SCI. We also found that this hyperalgesia occurred concurrently with an augmentation in systemic acrolein, detected by an acrolein-glutathione metabolite in the urine. The application of an acrolein scavenger, phenelzine, was shown to reduce the hyperalgesic effect of acrolein inhalation. The previously determined ability of acrolein to bind to and activate the TRPA1 channel and elicit algesic responses may be a mechanism of the phenomenon seen in this study. Upon the exposure to actual cigarette smoke after SCI, intensified neuropathic pain behaviors were also observed and persisted for at least 1week after the cessation of the exposure period. Taken together, these results indicate that cigarette smoke, through mechanisms involving acrolein, poses a threat to the vulnerable CNS after SCI and can contribute to neuropathic pain. This investigation also provides further evidence for the potential utility of acrolein scavengers as a therapeutic strategy in SCI-resultant neuropathic pain. Copyright © 2017. Published by Elsevier B.V.

Ovicidal activity of acrolein vapors to Indian meal moth eggs of various ages.

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Pourmirza, Ali Asghr

2007-09-01

The effect of acrolein vapors against carefully aged eggs of Indian meal moth at 27 +/- 1 and 17 +/- 1 degrees C at different dosage levels of acrolein over various exposure times was determined. Considerable variation in the susceptibility of different age groups of eggs was apparent in the fiducial limits of the LD50 values. At both temperatures and 24 h exposure period, eggs aged 1-2 day-old were more tolerant to acrolein than other age groups. In all bioassays, eggs exposed to higher dosages of acrolein developed at smaller rate. This was significant for the eggs, which were exposed to the highest dosage for 24 h. Increasing the temperature from 17 +/- 1 to 27 +/- 1 degrees C greatly increased the efficacy of acrolein. Overall, at 27 +/- 1 degrees C eggs of P. interpunctella were killed by less than one-fourth of the dosage required for control at 17 +/- 1 degrees C. Acrolein achieved 50% mortality with a dosage of 3.80 mg L(-1) in 1-2 day-old eggs at 27 +/- 1 degrees C. At this temperature hatching was retarded and greatly reduced when eggs aged 1-2 day-old were exposed to 32 mg L(-1) of acrolein for the 24 h exposure period. There was no evidence of a hatch delay longer than the time spent under vapors for eggs exposed at 17 +/- 1 or 27 +/- 1 degrees C, indicating that some development must have occurred under fumigation.

Protective effect of crocin on acrolein-induced tau phosphorylation in the rat brain.

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Rashedinia, Marzieh; Lari, Parisa; Abnous, Khalil; Hosseinzadeh, Hossein

2015-01-01

Acrolein, as a by-product of lipid peroxidation, is implicated in brain aging and in the pathogenesis of oxidative stressmediated neurodegenerative disorders such as Alzheimer's disease (AD). Widespread human exposure to the toxic environmental pollutant that is acrolein renders it necessary to evaluate the effects of exogenous acrolein on the brain. This study investigated the toxic effects of oral administration of 3 mg/kg/day acrolein on the rat cerebral cortex. Moreover, the neuroprotective effects of crocin, the main constituent of saffron, against acrolein toxicity were evaluated. We showed that acrolein decreased concentration of glutathione (GSH) and increased levels of malondialdehyde (MDA), Amyloid-beta (Abeta) and phospho-tau in the brain. Simultaneously, acrolein activated Mitogen-Activated Protein Kinases (MAPKs) signalling pathways. Co-administration of crocin significantly attenuated MDA, Abeta and p-tau levels by modulating MAPKs signalling pathways. Our data demonstrated that environmental exposure to acrolein triggers some molecular events which contribute to brain aging and neurodisorders. Additionally, crocin as an antioxidant is a promising candidate for treatment of neurodegenerative disorders, such as brain aging and AD.

Matrix metalloproteinase-14 mediates a phenotypic shift in the airways to increase mucin production.

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Deshmukh, Hitesh S; McLachlan, Anne; Atkinson, Jeffrey J; Hardie, William D; Korfhagen, Thomas R; Dietsch, Maggie; Liu, Yang; Di, Peter Y P; Wesselkamper, Scott C; Borchers, Michael T; Leikauf, George D

2009-11-01

Induced mainly by cigarette smoking, chronic obstructive pulmonary disease (COPD) is a global public health problem characterized by progressive difficulty in breathing and increased mucin production. Previously, we reported that acrolein levels found in COPD sputum could activate matrix metalloproteinase-9 (MMP9). To determine whether acrolein increases expression and activity of MMP14, a critical membrane-bound endopeptidase that can initial a MMP-activation cascade. MMP14 activity and adduct formation were measured following direct acrolein treatment. MMP14 expression and activity was measured in human airway epithelial cells. MMP14 immunohistochemistry was performed with COPD tissue, and in acrolein- or tobacco-exposed mice. In a cell-free system, acrolein, in concentrations equal to those found in COPD sputum, directly adducted cysteine 319 in the MMP14 hemopexin-like domain and activated MMP14. In cells, acrolein increased MMP14 activity, which was inhibited by a proprotein convertase inhibitor, hexa-d-arginine. In the airway epithelium of COPD subjects, immunoreactive MMP14 protein increased. In mouse lung, acrolein or tobacco smoke increased lung MMP14 activity and protein. In cells, acrolein-induced MMP14 transcripts were inhibited by an epidermal growth factor receptor (EGFR) neutralizing antibody, EGFR kinase inhibitor, metalloproteinase inhibitor, or mitogen-activated protein kinase (MAPK) 3/2 or MAPK8 inhibitors, but not a MAPK14 inhibitor. Decreasing the MMP14 protein and activity in vitro by small interfering (si)RNA to MMP14 diminished the acrolein-induced MUC5AC transcripts. In acrolein-exposed mice or transgenic mice with lung-specific transforming growth factor-alpha (an EGFR ligand) expression, lung MMP14 and MUC5AC levels increased and these effects were inhibited by a EGFR inhibitor, erlotinib. Taken together, these findings implicate acrolein-induced MMP14 expression and activity in mucin production in COPD.

Sirt3 confers protection against acrolein-induced oxidative stress in cochlear nucleus neurons.

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Qu, Juan; Wu, Yong-Xiang; Zhang, Ting; Qiu, Yang; Ding, Zhong-Jia; Zha, Ding-Jun

2018-03-01

Acrolein is a ubiquitous dietary and environmental pollutant, which can also be generated endogenously during cellular stress. However, the molecular mechanisms underlying acrolein-induced neurotoxicity, especially in ototoxicity conditions, have not been fully determined. In this study, we investigated the mechanisms on acrolein-induced toxicity in primary cultured cochlear nucleus neurons with focus on Sirt3, a mitochondrial deacetylase. We found that acrolein treatment induced neuronal injury and programmed cell death (PCD) in a dose dependent manner in cochlear nucleus neurons, which was accompanied by increased intracellular reactive oxygen species (ROS) generation and lipid peroxidation. Acrolein exposure also significantly reduced the mitochondrial membrane potential (MMP) levels, promoted cytochrome c release and decreased mitochondrial ATP production. In addition, increased ER tracker fluorescence and activation of ER stress factors were observed after acrolein treatment, and the ER stress inhibitors were shown to attenuate acrolein-induced toxicity in cochlear nucleus neurons. The results of western blot and RT-PCR showed that acrolein markedly decreased the expression of Sirt3 at both mRNA and protein levels, and reduced the activity of downstream mitochondrial enzymes. Furthermore, overexpression of Sirt3 by lentivirus transfection partially prevented acrolein-induced neuronal injury in cochlear nucleus neurons. These results demonstrated that acrolein induces mitochondrial dysfunction and ER stress in cochlear nucleus neurons, and Sirt3 acts as an endogenous protective factor in acrolein-induced ototoxicity. Copyright © 2017. Published by Elsevier Ltd.

Acrolein effects in pulmonary cells: relevance to chronic obstructive pulmonary disease.

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Moretto, Nadia; Volpi, Giorgia; Pastore, Fiorella; Facchinetti, Fabrizio

2012-07-01

Acrolein (2-propenal) is a highly reactive α,β-unsaturated aldehyde and a respiratory irritant that is ubiquitously present in the environment but that can also be generated endogenously at sites of inflammation. Acrolein is abundant in tobacco smoke, which is the major environmental risk factor for chronic obstructive pulmonary disease (COPD), and elevated levels of acrolein are found in the lung fluids of COPD patients. Its high electrophilicity makes acrolein notorious for its facile reaction with biological nucleophiles, leading to the modification of proteins and DNA and depletion of antioxidant defenses. As a consequence, acrolein results in oxidative stress as well as altered intracellular signaling and gene transcription/translation. In pulmonary cells, acrolein, at subtoxic concentrations, can activate intracellular stress kinases, alter the production of inflammatory mediators and proteases, modify innate immune response, induce mucus hypersecretion, and damage airway epithelium. A better comprehension of the mechanisms underlying acrolein effects in the airways may suggest novel treatment strategies in COPD. © 2012 New York Academy of Sciences.

Acrolein consumption induces systemic dyslipidemia and lipoprotein modification

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Conklin, Daniel J.; Barski, Oleg A.; Lesgards, Jean-Francois; Juvan, Peter; Rezen, Tadeja; Rozman, Damjana; Prough, Russell A.; Vladykovskaya, Elena; Liu, SiQi; Srivastava, Sanjay; Bhatnagar, Aruni

2010-01-01

Aldehydes such as acrolein are ubiquitous pollutants present in automobile exhaust, cigarette, wood, and coal smoke. Such aldehydes are also constituents of several food substances and are present in drinking water, irrigation canals, and effluents from manufacturing plants. Oral intake represents the most significant source of exposure to acrolein and related aldehydes. To study the effects of short-term oral exposure to acrolein on lipoprotein levels and metabolism, adult mice were gavage-fed 0.1 to 5 mg acrolein/kg bwt and changes in plasma lipoproteins were assessed. Changes in hepatic gene expression related to lipid metabolism and cytokines were examined by qRT-PCR analysis. Acrolein feeding did not affect body weight, blood urea nitrogen, plasma creatinine, electrolytes, cytokines or liver enzymes, but increased plasma cholesterol and triglycerides. Similar results were obtained with apoE-null mice. Plasma lipoproteins from acrolein-fed mice showed altered electrophoretic mobility on agarose gels. Chromatographic analysis revealed elevated VLDL cholesterol, phospholipids, and triglycerides levels with little change in LDL or HDL. NMR analysis indicated shifts from small to large VLDL and from large to medium-small LDL with no change in the size of HDL particles. Increased plasma VLDL was associated with a significant decrease in post-heparin plasma hepatic lipase activity and a decrease in hepatic expression of hepatic lipase. These observations suggest that oral exposure to acrolein could induce or exacerbate systemic dyslipidemia and thereby contribute to cardiovascular disease risk.

Acrolein consumption induces systemic dyslipidemia and lipoprotein modification

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Conklin, Daniel J., E-mail: dj.conklin@louisville.ed [Diabetes and Obesity Center, University of Louisville, Louisville, KY 40202 (United States); Barski, Oleg A; Lesgards, Jean-Francois [Diabetes and Obesity Center, University of Louisville, Louisville, KY 40202 (United States); Juvan, Peter; Rezen, Tadeja; Rozman, Damjana [Centre for Functional Genomics and Bio-Chips (CFGBC), Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Zaloska 4, SI-1000 Ljubljana (Slovenia); Prough, Russell A [Department of Biochemistry and Molecular Biology, University of Louisville, Louisville, KY 40202 (United States); Vladykovskaya, Elena; Liu, SiQi; Srivastava, Sanjay [Diabetes and Obesity Center, University of Louisville, Louisville, KY 40202 (United States); Bhatnagar, Aruni [Diabetes and Obesity Center, University of Louisville, Louisville, KY 40202 (United States); Department of Biochemistry and Molecular Biology, University of Louisville, Louisville, KY 40202 (United States)

2010-02-15

Aldehydes such as acrolein are ubiquitous pollutants present in automobile exhaust, cigarette, wood, and coal smoke. Such aldehydes are also constituents of several food substances and are present in drinking water, irrigation canals, and effluents from manufacturing plants. Oral intake represents the most significant source of exposure to acrolein and related aldehydes. To study the effects of short-term oral exposure to acrolein on lipoprotein levels and metabolism, adult mice were gavage-fed 0.1 to 5 mg acrolein/kg bwt and changes in plasma lipoproteins were assessed. Changes in hepatic gene expression related to lipid metabolism and cytokines were examined by qRT-PCR analysis. Acrolein feeding did not affect body weight, blood urea nitrogen, plasma creatinine, electrolytes, cytokines or liver enzymes, but increased plasma cholesterol and triglycerides. Similar results were obtained with apoE-null mice. Plasma lipoproteins from acrolein-fed mice showed altered electrophoretic mobility on agarose gels. Chromatographic analysis revealed elevated VLDL cholesterol, phospholipids, and triglycerides levels with little change in LDL or HDL. NMR analysis indicated shifts from small to large VLDL and from large to medium-small LDL with no change in the size of HDL particles. Increased plasma VLDL was associated with a significant decrease in post-heparin plasma hepatic lipase activity and a decrease in hepatic expression of hepatic lipase. These observations suggest that oral exposure to acrolein could induce or exacerbate systemic dyslipidemia and thereby contribute to cardiovascular disease risk.

Acrolein Can Cause Cardiovascular Disease: A Review.

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Henning, Robert J; Johnson, Giffe T; Coyle, Jayme P; Harbison, Raymond D

2017-07-01

Acrolein is a highly reactive unsaturated aldehyde that is formed during the burning of gasoline and diesel fuels, cigarettes, woods and plastics. In addition, acrolein is generated during the cooking or frying of food with fats or oils. Acrolein is also used in the synthesis of many organic chemicals and as a biocide in agricultural and industrial water supply systems. The total emissions of acrolein in the United States from all sources are estimated to be 62,660 tons/year. Acrolein is classified by the Environmental Protection Agency as a high-priority air and water toxicant. Acrolein can exert toxic effects following inhalation, ingestion, and dermal exposures that are dose dependent. Cardiovascular tissues are particularly sensitive to the toxic effects of acrolein based primarily on in vitro and in vivo studies. Acrolein can generate free oxygen radical stress in the heart, decrease endothelial nitric oxide synthase phosphorylation and nitric oxide formation, form cytoplasmic and nuclear protein adducts with myocyte and vascular endothelial cell proteins and cause vasospasm. In this manner, chronic exposure to acrolein can cause myocyte dysfunction, myocyte necrosis and apoptosis and ultimately lead to cardiomyopathy and cardiac failure. Epidemiological studies of acrolein exposure and toxicity should be developed and treatment strategies devised that prevent or significantly limit acrolein cardiovascular toxicity.

Metabolic shift in lung alveolar cell mitochondria following acrolein exposure.

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Agarwal, Amit R; Yin, Fei; Cadenas, Enrique

2013-11-15

Acrolein, an α,β unsaturated electrophile, is an environmental pollutant released in ambient air from diesel exhausts and cooking oils. This study examines the role of acrolein in altering mitochondrial function and metabolism in lung-specific cells. RLE-6TN, H441, and primary alveolar type II (pAT2) cells were exposed to acrolein for 4 h, and its effect on mitochondrial oxygen consumption rates was studied by XF Extracellular Flux analysis. Low-dose acrolein exposure decreased mitochondrial respiration in a dose-dependent manner because of alteration in the metabolism of glucose in all the three cell types. Acrolein inhibited glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity, leading to decreased substrate availability for mitochondrial respiration in RLE-6TN, H441, and pAT2 cells; the reduced GAPDH activity was compensated in pAT2 cells by an increase in the activity of glucose-6-phosphate dehydrogenase, the regulatory control of the pentose phosphate pathway. The decrease in pyruvate from glucose metabolism resulted in utilization of alternative sources to support mitochondrial energy production: palmitate-BSA complex increased mitochondrial respiration in RLE-6TN and pAT2 cells. The presence of palmitate in alveolar cells for surfactant biosynthesis may prove to be the alternative fuel source for mitochondrial respiration. Accordingly, a decrease in phosphatidylcholine levels and an increase in phospholipase A2 activity were found in the alveolar cells after acrolein exposure. These findings have implications for understanding the decrease in surfactant levels frequently observed in pathophysiological situations with altered lung function following exposure to environmental toxicants.

Environmental toxin acrolein alters levels of endogenous lipids, including TRP agonists: A potential mechanism for headache driven by TRPA1 activation

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Emma Leishman

2017-01-01

Full Text Available Exposure to airborne toxins can trigger headaches, but the mechanisms are not well understood. Some environmental toxins, such as acrolein, activate transient receptor potential ankyrin 1 (TRPA1, a receptor involved in pain sensation that is highly expressed in the trigeminovascular system. It has been shown in rat models that repeated exposure to acrolein induces trigeminovascular sensitization to both TRPA1 and TRP vanilloid 1 (TRPV1 agonists, a phenomenon linked to headache. In this study, we test the hypothesis that the sensitization of trigeminovascular responses in rats after acrolein exposure via inhalation is associated with changes in levels of endogenous lipids, including TRPV1 agonists, in the trigeminal ganglia, trigeminal nucleus, and cerebellum. Lipidomics analysis of 80 lipids was performed on each tissue after acute acrolein, chronic acrolein, or room air control. Both acute and chronic acrolein exposure drove widespread alterations in lipid levels. After chronic acrolein exposure, levels of all 6 N-acyl ethanolamines in the screening library, including the endogenous cannabinoid and TRPV1 agonist, N-arachidonoyl ethanolamine, were elevated in trigeminal tissue and in the cerebellum. This increase in TRPV1 ligands by acrolein exposure may indicate further downstream signaling, in that we also show here that a combination of these TRPV1 endogenous agonists increases the potency of the individual ligands in TRPV1-HEK cells. In addition to these TRPV1 agonists, 3 TRPV3 antagonists, 4 TRPV4 agonists, and 25 orphan lipids were up and down regulated after acrolein exposure. These data support the hypothesis that lipid signaling may represent a mechanism by which repeated exposure to the TRPA1 agonist and environmental toxin, acrolein, drives trigeminovascular sensitization. Keywords: Lipidomics, Endogenous cannabinoid, TRPA1, TRPV1, Lipoamine, Acrolein, Migraine

Acute Acrolein Exposure Induces Impairment of Vocal Fold Epithelial Barrier Function.

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Xinxin Liu

Full Text Available Acrolein is a ubiquitous pollutant abundant in cigarette smoke, mobile exhaust, and industrial waste. There is limited literature on the effects of acrolein on vocal fold tissue, although there are clinical reports of voice changes after pollutant exposures. Vocal folds are responsible for voice production. The overall objective of this study was to investigate the effects of acrolein exposure on viable, excised vocal fold epithelial tissue and to characterize the mechanism underlying acrolein toxicity. Vocal fold epithelia were studied because they form the outermost layer of the vocal folds and are a primary recipient of inhaled pollutants. Porcine vocal fold epithelia were exposed to 0, 50, 100, 500, 900 or 1300 μM of acrolein for 3 hours; the metabolic activity, epithelial resistance, epithelial permeability, tight junction protein (occludin and claudin 3 expression, cell membrane integrity and lipid peroxidation were investigated. The data demonstrated that acrolein exposure at 500 μM significantly reduced vocal fold epithelial metabolic activity by 27.2% (p≤0.001. Incubation with 100 μM acrolein caused a marked increase in epithelial permeability by 130.5% (p<0.05 and a reduction in transepithelial electrical resistance (TEER by 180.0% (p<0.001. While the expression of tight junctional protein did not change in acrolein-treated samples, the cell membrane integrity was significantly damaged with a 45.6% increase of lipid peroxidation as compared to controls (p<0.05. Taken together, these data provide evidence that acute acrolein exposure impairs vocal fold epithelial barrier integrity. Lipid peroxidation-induced cell membrane damage may play an important role in reducing the barrier function of the epithelium.

The effects of acetaldehyde and acrolein on muscle catabolism in C2 myotubes.

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Rom, Oren; Kaisari, Sharon; Aizenbud, Dror; Reznick, Abraham Z

2013-12-01

The toxic aldehydes acetaldehyde and acrolein were previously suggested to damage skeletal muscle. Several conditions in which exposure to acetaldehyde and acrolein is increased were associated with muscle wasting and dysfunction. These include alcoholic myopathy, renal failure, oxidative stress, and inflammation. A main exogenous source of both acetaldehyde and acrolein is cigarette smoking, which was previously associated with increased muscle catabolism. Recently, we have shown that exposure of skeletal myotubes to cigarette smoke stimulated muscle catabolism via increased oxidative stress, activation of p38 MAPK, and upregulation of muscle-specific E3 ubiquitin ligases. In this study, we aimed to investigate the effects of acetaldehyde and acrolein on catabolism of skeletal muscle. Skeletal myotubes differentiated from the C2 myoblast cell line were exposed to acetaldehyde or acrolein and their effects on signaling pathways related to muscle catabolism were studied. Exposure of myotubes to acetaldehyde did not promote muscle catabolism. However, exposure to acrolein caused increased generation of free radicals, activation of p38 MAPK, upregulation of the muscle-specific E3 ligases atrogin-1 and MuRF1, degradation of myosin heavy chain, and atrophy of myotubes. Inhibition of p38 MAPK by SB203580 abolished acrolein-induced muscle catabolism. Our findings demonstrate that acrolein but not acetaldehyde activates a signaling cascade resulting in muscle catabolism in skeletal myotubes. Although within the limitations of an in vitro study, these findings indicate that acrolein may promote muscle wasting in conditions of increased exposure to this aldehyde. Copyright © 2013 Elsevier Inc. All rights reserved.

Acute Acrolein Exposure Induces Impairment of Vocal Fold Epithelial Barrier Function.

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Liu, Xinxin; Zheng, Wei; Sivasankar, M Preeti

2016-01-01

Acrolein is a ubiquitous pollutant abundant in cigarette smoke, mobile exhaust, and industrial waste. There is limited literature on the effects of acrolein on vocal fold tissue, although there are clinical reports of voice changes after pollutant exposures. Vocal folds are responsible for voice production. The overall objective of this study was to investigate the effects of acrolein exposure on viable, excised vocal fold epithelial tissue and to characterize the mechanism underlying acrolein toxicity. Vocal fold epithelia were studied because they form the outermost layer of the vocal folds and are a primary recipient of inhaled pollutants. Porcine vocal fold epithelia were exposed to 0, 50, 100, 500, 900 or 1300 μM of acrolein for 3 hours; the metabolic activity, epithelial resistance, epithelial permeability, tight junction protein (occludin and claudin 3) expression, cell membrane integrity and lipid peroxidation were investigated. The data demonstrated that acrolein exposure at 500 μM significantly reduced vocal fold epithelial metabolic activity by 27.2% (p≤0.001). Incubation with 100 μM acrolein caused a marked increase in epithelial permeability by 130.5% (pacrolein-treated samples, the cell membrane integrity was significantly damaged with a 45.6% increase of lipid peroxidation as compared to controls (pacrolein exposure impairs vocal fold epithelial barrier integrity. Lipid peroxidation-induced cell membrane damage may play an important role in reducing the barrier function of the epithelium.

Polyamine modification by acrolein exclusively produces 1,5-diazacyclooctanes: a previously unrecognized mechanism for acrolein-mediated oxidative stress.

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Tsutsui, Ayumi; Imamaki, Rie; Kitazume, Shinobu; Hanashima, Shinya; Yamaguchi, Yoshiki; Kaneda, Masato; Oishi, Shinya; Fujii, Nobutaka; Kurbangalieva, Almira; Taniguchi, Naoyuki; Tanaka, Katsunori

2014-07-28

Acrolein, a toxic unsaturated aldehyde generated as a result of oxidative stress, readily reacts with a variety of nucleophilic biomolecules. Polyamines, which produced acrolein in the presence of amine oxidase, were then found to react with acrolein to produce 1,5-diazacyclooctane, a previously unrecognized but significant downstream product of oxidative stress. Although diazacyclooctane formation effectively neutralized acrolein toxicity, the diazacyclooctane hydrogel produced through a sequential diazacyclooctane polymerization reaction was highly cytotoxic. This study suggests that diazacyclooctane formation is involved in the mechanism underlying acrolein-mediated oxidative stress.

The Effects of Acrolein on the Thioredoxin System: Implications for Redox-Sensitive Signaling

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Myers, Charles R.; Myers, Judith M.; Kufahl, Timothy D.; Forbes, Rachel; Szadkowski, Adam

2012-01-01

The reactive aldehyde acrolein is a ubiquitous environmental pollutant and is also generated endogenously. It is a strong electrophile and reacts rapidly with nucleophiles including thiolates. This review focuses on the effects of acrolein on thioredoxin reductase (TrxR) and thioredoxin (Trx), which are major regulators of intracellular protein thiol redox balance. Acrolein causes irreversible effects on TrxR and Trx, which are consistent with the formation of covalent adducts to selenocysteine and cysteine residues that are key to their activity. TrxR and Trx are more sensitive than some other redox-sensitive proteins, and their prolonged inhibition could disrupt a number of redox-sensitive functions in cells. Among these effects are the oxidation of peroxiredoxins and the activation of apoptosis signal regulating kinase (ASK1). ASK1 promotes MAP kinase activation, and p38 activation contributes to apoptosis and a number of other acrolein-induced stress responses. Overall, the disruption of the TrxR/Trx system by acrolein could be significant early and prolonged events that affects many aspects of redox-sensitive signaling and oxidant stress. PMID:21812108

Brain infarction correlates more closely with acrolein than with reactive oxygen species.

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Saiki, Ryotaro; Park, Hyerim; Ishii, Itsuko; Yoshida, Madoka; Nishimura, Kazuhiro; Toida, Toshihiko; Tatsukawa, Hideki; Kojima, Soichi; Ikeguchi, Yoshihiko; Pegg, Anthony E; Kashiwagi, Keiko; Igarashi, Kazuei

2011-01-28

Although it is thought that the major factor responsible for cell damage is reactive oxygen species (ROS), our recent studies have shown that acrolein is more toxic than ROS. Thus, the relative importance of acrolein and ROS in cell damage during brain infarction was compared using photochemically induced thrombosis model mice. The levels of acrolein-conjugated albumin, and of 4-hydroxynonenal (HNE)-conjugated albumin and 8-OHdG were evaluated as indicators of damage produced by acrolein and ROS, respectively. The increase in acrolein-conjugated albumin was much greater than the increase in HNE-conjugated albumin or 8-OHdG, suggesting that acrolein is more strongly involved in cell damage than ROS during brain infarction. It was also shown that infarction led more readily to RNA damage than to DNA or phospholipid damage. As a consequence, polyamines were released from RNA, and acrolein was produced from polyamines, especially from spermine by spermine oxidase. Production of acrolein from spermine by spermine oxidase was clarified using spermine synthase-deficient Gy mice and transglutaminase 2-knockout mice, in which spermine content is negligible or spermidine/spermine N(1)-acetyltransferase activity is elevated. Copyright © 2010 Elsevier Inc. All rights reserved.

Acrolein induces vasodilatation of rodent mesenteric bed via an EDHF-dependent mechanism

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Awe, S.O.; Adeagbo, A.S.O.; D'Souza, S.E.; Bhatnagar, A.; Conklin, D.J.

2006-01-01

Acrolein is generated endogenously during lipid peroxidation and inflammation and is an environmental pollutant. Protein adducts of acrolein are detected in atherosclerotic plaques and neurons of patients with Alzheimer's disease. To understand vascular effects of acrolein exposure, we studied acrolein vasoreactivity in perfused rodent mesenteric bed. Acrolein induced endothelium-dependent vasodilatation that was more robust and more sensitive than dilation induced by 4-hydroxy-trans-2-nonenal, trans-2-hexenal, or propionaldehyde. Acrolein-induced vasodilatation was mediated by K + -sensitive components, e.g., it was abolished in 0 [K + ] o buffer or in 3 mM tetrabutylammonium, inhibited 75% in 50 μM ouabain, and inhibited 64% in 20 mM K + buffer. Moreover, combined treatment with the Ca 2+ -activated K + channel inhibitors 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34, 100 nM) and apamin (5 μM) significantly reduced vasodilatation without altering sensitivity to acrolein. However, acrolein-induced % dilation was unaffected by L-NAME or indomethacin pretreatment indicating mechanistic independence of NO and prostaglandins. Moreover, acrolein induced vasodilatation in cirazoline-precontracted mesenteric bed of eNOS-null mice confirming eNOS independence. Pretreatment with 6-(2-propargyloxyphenyl) hexanoic acid (PPOH 50 μM), an epoxygenase inhibitor, or the superoxide dismutase mimetic Tempol (100 μM) significantly attenuated acrolein-induced vasodilatation. Collectively, these data indicate that acrolein stimulates mesenteric bed vasodilatation due to endothelium-derived signal(s) that is K + -, ouabain-, PPOH-, and Tempol-sensitive, and thus, a likely endothelium-derived hyperpolarizing factor (EDHF). These data indicate that low level acrolein exposure associated with vascular oxidative stress or inflammation stimulates vasodilatation via EDHF release in medium-sized arteries - a novel function

The tobacco smoke component acrolein induces glucocorticoid resistant gene expression via inhibition of histone deacetylase.

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Randall, Matthew J; Haenen, Guido R M M; Bouwman, Freek G; van der Vliet, Albert; Bast, Aalt

2016-01-05

Chronic obstructive pulmonary disease (COPD) is the leading cause of cigarette smoke-related death worldwide. Acrolein, a crucial reactive electrophile found in cigarette smoke mimics many of the toxic effects of cigarette smoke-exposure in the lung. In macrophages, cigarette smoke is known to hinder histone deacetylases (HDACs), glucocorticoid-regulated enzymes that play an important role in the pathogenesis of glucocorticoid resistant inflammation, a common feature of COPD. Thus, we hypothesize that acrolein plays a role in COPD-associated glucocorticoid resistance. To examine the role of acrolein on glucocorticoid resistance, U937 monocytes, differentiated with PMA to macrophage-like cells were treated with acrolein for 0.5h followed by stimulation with hydrocortisone for 8h, or treated simultaneously with LPS and hydrocortisone for 8h without acrolein. GSH and nuclear HDAC activity were measured, or gene expression was analyzed by qPCR. Acrolein-mediated TNFα gene expression was not suppressed by hydrocortisone whereas LPS-induced TNFα expression was suppressed. Acrolein also significantly inhibited nuclear HDAC activity in macrophage-like cells. Incubation of recombinant HDAC2 with acrolein led to the formation of an HDAC2-acrolein adduct identified by mass spectrometry. Therefore, these results suggest that acrolein-induced inflammatory gene expression is resistant to suppression by the endogenous glucocorticoid, hydrocortisone. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Acrolein inhibits cytokine gene expression by alkylating cysteine and arginine residues in the NF-kappaB1 DNA binding domain.

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Lambert, Cherie; Li, Jimei; Jonscher, Karen; Yang, Teng-Chieh; Reigan, Philip; Quintana, Megan; Harvey, Jean; Freed, Brian M

2007-07-06

Cigarette smoke is a potent inhibitor of pulmonary T cell responses, resulting in decreased immune surveillance and an increased incidence of respiratory tract infections. The alpha,beta-unsaturated aldehydes in cigarette smoke (acrolein and crotonaldehyde) inhibited production of interleukin-2 (IL-2), IL-10, granulocyte-macrophage colony-stimulating factor, interferon-gamma, and tumor necrosis factor-alpha by human T cells but did not inhibit production of IL-8. The saturated aldehydes (acetaldehyde, propionaldehyde, and butyraldehyde) in cigarette smoke were inactive. Acrolein inhibited induction of NF-kappaB DNA binding activity after mitogenic stimulation of T cells but had no effect on induction of NFAT or AP-1. Acrolein inhibited NF-kappaB1 (p50) binding to the IL-2 promoter in a chromatin immunoprecipitation assay by >99%. Using purified recombinant p50 in an electrophoretic mobility shift assay, we demonstrated that acrolein was 2000-fold more potent than crotonaldehyde in blocking DNA binding to an NF-kappaB consensus sequence. Matrix-assisted laser desorption/ionization time-of-flight and tandem mass spectrometry demonstrated that acrolein alkylated two amino acids (Cys-61 and Arg-307) in the DNA binding domain. Crotonaldehyde reacted with Cys-61, but not Arg-307, whereas the saturated aldehydes in cigarette smoke did not react with p50. These experiments demonstrate that aldehydes in cigarette smoke can regulate gene expression by direct modification of a transcription factor.

Acrolein exposure is associated with increased cardiovascular disease risk.

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DeJarnett, Natasha; Conklin, Daniel J; Riggs, Daniel W; Myers, John A; O'Toole, Timothy E; Hamzeh, Ihab; Wagner, Stephen; Chugh, Atul; Ramos, Kenneth S; Srivastava, Sanjay; Higdon, Deirdre; Tollerud, David J; DeFilippis, Andrew; Becher, Carrie; Wyatt, Brad; McCracken, James; Abplanalp, Wes; Rai, Shesh N; Ciszewski, Tiffany; Xie, Zhengzhi; Yeager, Ray; Prabhu, Sumanth D; Bhatnagar, Aruni

2014-08-06

Acrolein is a reactive aldehyde present in high amounts in coal, wood, paper, and tobacco smoke. It is also generated endogenously by lipid peroxidation and the oxidation of amino acids by myeloperoxidase. In animals, acrolein exposure is associated with the suppression of circulating progenitor cells and increases in thrombosis and atherogenesis. The purpose of this study was to determine whether acrolein exposure in humans is also associated with increased cardiovascular disease (CVD) risk. Acrolein exposure was assessed in 211 participants of the Louisville Healthy Heart Study with moderate to high (CVD) risk by measuring the urinary levels of the major acrolein metabolite-3-hydroxypropylmercapturic acid (3-HPMA). Generalized linear models were used to assess the association between acrolein exposure and parameters of CVD risk, and adjusted for potential demographic confounders. Urinary 3-HPMA levels were higher in smokers than nonsmokers and were positively correlated with urinary cotinine levels. Urinary 3-HPMA levels were inversely related to levels of both early (AC133(+)) and late (AC133(-)) circulating angiogenic cells. In smokers as well as nonsmokers, 3-HPMA levels were positively associated with both increased levels of platelet-leukocyte aggregates and the Framingham Risk Score. No association was observed between 3-HPMA and plasma fibrinogen. Levels of C-reactive protein were associated with 3-HPMA levels in nonsmokers only. Regardless of its source, acrolein exposure is associated with platelet activation and suppression of circulating angiogenic cell levels, as well as increased CVD risk. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Acrolein-Induced Dyslipidemia and Acute Phase Response Independenly of HMG-CoA Reductase

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Conklin, Daniel J.; Prough, Russell A.; Juvan, Peter; Rezen, Tadeja; Rozman, Damjana; Haberzettl, Petra; Srivastava, Sanjay; Bhatnagar, Aruni

2012-01-01

Scope Aldehydes are ubiquitous natural constituents of foods, water and beverages. Dietary intake represents the greatest source of exposure to acrolein and related aldehydes. Oral acrolein induces dyslipidemia acutely and chronically increases atherosclerosis in mice, yet the mechanisms are unknown. Because lipid synthesis and trafficking are largely under hepatic control, we examined hepatic genes in murine models of acute and chronic oral acrolein exposure. Methods and results Changes in hepatic gene expression were examined using a Steroltalk microarray. Acute acrolein feeding modified plasma and hepatic proteins and increased plasma triglycerides within 15 min. By 6h, acrolein altered hepatic gene expression including Insig1, Insig2 and Hmgcr genes and stimulated an acute phase response (APR) with up-regulation of serum amyloid A genes (Saa) and systemic hypoalbuminemia. To test if decreased HMG-CoA reductase activity could modify acrolein-induced dyslipidemia or the APR, mice were pretreated with simvastatin. Statin treatment, however, did not alter acrolein-induced dyslipidemia or hypoalbuminemia associated with an APR. Few hepatic genes were dysregulated by chronic acrolein feeding in apoE-null mice. These studies confirmed that acute acrolein exposure altered expression of hepatic genes involved with lipid synthesis and trafficking and APR, and thus, indicated a hepatic locus of acrolein-induced dyslipidemia and APR that was independent of HMG CoA-reductase. Conclusion Dietary intake of acrolein could contribute to cardiovascular disease risk by disturbing hepatic function. PMID:21812109

The Uremic Toxin Acrolein Promotes Suicidal Erythrocyte Death

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Mohamed Siyabeldin E. Ahmed

2013-05-01

Full Text Available Background: Anemia is a major complication of end stage renal disease. The anemia is mainly the result of impaired formation of erythrocytes due to lack of erythropoietin and iron deficiency. Compelling evidence, however, points to the contribution of accelerated erythrocyte death, which decreases the life span of circulating erythrocytes. Erythrocytes may enter suicidal death or eryptosis, which is characterized by cell shrinkage and by cell membrane scrambling with phosphatidylserine-exposure at the erythrocyte surface. Triggers of eryptosis include increase of cytosolic Ca2+-activity ([Ca2+]i. Erythrocytes could be sensitized to cytosolic Ca2+ by ceramide. In end stage renal disease, eryptosis may possibly be stimulated by uremic toxins. The present study explored, whether the uremic toxin acrolein could trigger eryptosis. Methods: Cell volume was estimated from forward scatter, phosphatidylserine-exposure from annexin-V-binding, hemolysis from hemoglobin release, [Ca2+]i from Fluo3-fluorescence, and ceramide from fluorescent antibodies. Results: A 48 h exposure to acrolein (30 － 50 µM did not significantly modify [Ca2+]i but significantly decreased forward scatter and increased annexin-V-binding. Acrolein further triggered slight, but significant hemolysis and increased ceramide formation in erythrocytes. Acrolein (50 µM induced annexin-V-binding was significantly blunted in the nominal absence of extracellular Ca2+. Acrolein augmented the annexin-V-binding following treatment with Ca2+ ionophore ionomycin (1 µM. Conclusion: Acrolein stimulates suicidal erythrocyte death or eryptosis, an effect at least in part due to stimulation of ceramide formation with subsequent sensitisation of the erythrocytes to cytosolic Ca2+.

Inhibition of acrolein-stimulated MUC5AC expression by Platycodon grandiflorum root-derived saponin in A549 cells.

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Choi, Jae Ho; Hwang, Yong Pil; Han, Eun Hee; Kim, Hyung Gyun; Park, Bong Hwan; Lee, Hyun Sun; Park, Byung Keun; Lee, Young Chun; Chung, Young Chul; Jeong, Hye Gwang

2011-09-01

Mucin overproduction is a hallmark of chronic airway diseases such as chronic obstructive pulmonary disease. In this study, we investigated the inhibition of acrolein-induced expression of mucin 5, subtypes A and C (MUC5AC) by Changkil saponin (CKS) in A549 cells. Acrolein, a known toxin in tobacco smoke and an endogenous mediator of oxidative stress, increases the expression of airway MUC5AC, a major component of airway mucus. CKS, a Platycodon grandiflorum root-derived saponin, inhibited acrolein-induced MUC5AC expression and activity, through the suppression of NF-κB activation. CKS also repressed acrolein-induced phosphorylation of ERK1/2, JNK1/2, and p38MAPK, which are upstream signaling molecules that control MUC5AC expression. In addition, the MAPK inhibitors PD98059 (ERK1/2), SP600125 (JNK1/2), and SB203580 (p38 MAPK), and a PKC delta inhibitor (rottlerin; PKCδ) inhibited acrolein-induced MUC5AC expression and activity. CKS repressed acrolein-induced phosphorylation of PKCδ. Moreover, a reactive oxygen species (ROS) inhibitor, N-acetylcysteine, inhibited acrolein-induced MUC5AC expression and activity through the suppression of PKCδ and MAPK activation, and CKS repressed acrolein-induced ROS production. These results suggest that CKS suppresses acrolein-induced MUC5AC expression by inhibiting the activation of NF-κB via ROS-PKCδ-MAPK signaling. Copyright © 2011 Elsevier Ltd. All rights reserved.

Acrolein inhalation alters myocardial synchrony and performance at and below exposure concentrations that cause ventilatory responses

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Acrolein is an irritating aldehyde generated during combustion of organic compounds. Altered autonomic activity has been documented following acrolein inhalation, possibly impacting myocardial synchrony and function. Given the ubiquitous nature of acrolein in the environment, we ...

Environmental risk limits for acrolein

NARCIS (Netherlands)

Bodar CWM; SEC

2008-01-01

Dit rapport geeft milieurisicogrenzen voor acroleine in (grond)water, bodem en lucht. Milieurisicogrenzen zijn de technisch-wetenschappelijke advieswaarden voor de uiteindelijke milieukwaliteitsnormen in Nederland. De milieurisicogrenzen voor acroleine zijn gebaseerd op de uitkomsten van de EU

Acrolein-exposed normal human lung fibroblasts in vitro: cellular senescence, enhanced telomere erosion, and degradation of Werner's syndrome protein.

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Jang, Jun-Ho; Bruse, Shannon; Huneidi, Salam; Schrader, Ronald M; Monick, Martha M; Lin, Yong; Carter, A Brent; Klingelhutz, Aloysius J; Nyunoya, Toru

2014-09-01

Acrolein is a ubiquitous environmental hazard to human health. Acrolein has been reported to activate the DNA damage response and induce apoptosis. However, little is known about the effects of acrolein on cellular senescence. We examined whether acrolein induces cellular senescence in cultured normal human lung fibroblasts (NHLF). We cultured NHLF in the presence or absence of acrolein and determined the effects of acrolein on cell proliferative capacity, senescence-associated β-galactosidase activity, the known senescence-inducing pathways (e.g., p53, p21), and telomere length. We found that acrolein induced cellular senescence by increasing both p53 and p21. The knockdown of p53 mediated by small interfering RNA (siRNA) attenuated acrolein-induced cellular senescence. Acrolein decreased Werner's syndrome protein (WRN), a member of the RecQ helicase family involved in DNA repair and telomere maintenance. Acrolein-induced down-regulation of WRN protein was rescued by p53 knockdown or proteasome inhibition. Finally, we found that acrolein accelerated p53-mediated telomere shortening. These results suggest that acrolein induces p53-mediated cellular senescence accompanied by enhanced telomere attrition and WRN protein down-regulation.

Acrolein generation stimulates hypercontraction in isolated human blood vessels

International Nuclear Information System (INIS)

Conklin, D.J.; Bhatnagar, A.; Cowley, H.R.; Johnson, G.H.; Wiechmann, R.J.; Sayre, L.M.; Trent, M.B.; Boor, P.J.

2006-01-01

Increased risk of vasospasm, a spontaneous hyperconstriction, is associated with atherosclerosis, cigarette smoking, and hypertension-all conditions involving oxidative stress, lipid peroxidation, and inflammation. To test the role of the lipid peroxidation- and inflammation-derived aldehyde, acrolein, in human vasospasm, we developed an ex vivo model using human coronary artery bypass graft (CABG) blood vessels and a demonstrated acrolein precursor, allylamine. Allylamine induces hypercontraction in isolated rat coronary artery in a semicarbazide-sensitive amine oxidase activity (SSAO) dependent manner. Isolated human CABG blood vessels (internal mammary artery, radial artery, saphenous vein) were used to determine: (1) vessel responses and sensitivity to acrolein, allylamine, and H 2 O 2 exposure (1 μM-1 mM), (2) SSAO dependence of allylamine-induced effects using SSAO inhibitors (semicarbazide, 1 mM; MDL 72274-E, active isomer; MDL 72274-Z, inactive isomer; 100 μM), (3) the vasoactive effects of two other SSAO amine substrates, benzylamine and methylamine, and (4) the contribution of extracellular Ca 2+ to hypercontraction. Acrolein or allylamine but not H 2 O 2 , benzylamine, or methylamine stimulated spontaneous and pharmacologically intractable hypercontraction in CABG blood vessels that was similar to clinical vasospasm. Allylamine-induced hypercontraction and blood vessel SSAO activity were abolished by pretreatment with semicarbazide or MDL 72274-E but not by MDL 72274-Z. Allylamine-induced hypercontraction also was significantly attenuated in Ca 2+ -free buffer. In isolated aorta of spontaneously hypertensive rat, allylamine-induced an SSAO-dependent contraction and enhanced norepinephrine sensitivity but not in Sprague-Dawley rat aorta. We conclude that acrolein generation in the blood vessel wall increases human susceptibility to vasospasm, an event that is enhanced in hypertension

Modification and inactivation of Cu,Zn-superoxide dismutase by the lipid peroxidation product, acrolein

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Jung Hoon Kang

2013-11-01

Full Text Available Acrolein is the most reactive aldehydic product of lipidperoxidation and is found to be elevated in the brain whenoxidative stress is high. The effects of acrolein on the structureand function of human Cu,Zn-superoxide dismutase (SOD wereexamined. When Cu,Zn-SOD was incubated with acrolein, thecovalent crosslinking of the protein was increased, and the loss ofenzymatic activity was increased in a dose-dependent manner.Reactive oxygen species (ROS scavengers and copper chelatorsinhibited the acrolein-mediated Cu,Zn-SOD modification and theformation of carbonyl compound. The present study shows thatROS may play a critical role in acrolein-induced Cu,Zn-SODmodification and inactivation. When Cu,Zn-SOD that has beenexposed to acrolein was subsequently analyzed by amino acidanalysis, serine, histidine, arginine, threonine and lysine residueswere particularly sensitive. It is suggested that the modificationand inactivation of Cu,Zn-SOD by acrolein could be produced bymore oxidative cell environments. [BMB Reports 2013; 46(11:555-560

The effects of acrolein on peroxiredoxins, thioredoxins, and thioredoxin reductase in human bronchial epithelial cells

International Nuclear Information System (INIS)

Myers, Charles R.; Myers, Judith M.

2009-01-01

Inhalation is a common form of exposure to acrolein, a toxic reactive volatile aldehyde that is a ubiquitous environmental pollutant. Bronchial epithelial cells would be directly exposed to inhaled acrolein. The thioredoxin (Trx) system is essential for the maintenance of cellular thiol redox balance, and is critical for cell survival. Normally, thioredoxin reductase (TrxR) maintains the cytosolic (Trx1) and mitochondrial (Trx2) thioredoxins in the reduced state, and the thioredoxins keep the peroxiredoxins (Prx) reduced, thereby supporting their peroxidase function. The effects of acrolein on TrxR, Trx and Prx in human bronchial epithelial (BEAS-2B) cells were determined. A 30-min exposure to 5 μM acrolein oxidized both Trx1 and Trx2, although significant effects were noted for Trx1 at even lower acrolein concentrations. The effects on Trx1 and Trx2 could not be reversed by treatment with disulfide reductants. TrxR activity was inhibited 60% and >85% by 2.5 and 5 μM acrolein, respectively. The endogenous electron donor for TrxR, NADPH, could not restore its activity, and activity did not recover in cells during a 4-h acrolein-free period in complete medium. The effects of acrolein on TrxR and Trx therefore extend beyond the duration of exposure. While there was a strong correlation between TrxR inhibition and Trx1 oxidation, the irreversible effects on Trx1 suggest direct effects of acrolein rather than loss of reducing equivalents from TrxR. Trx2 did not become oxidized until ≥90% of TrxR was inhibited, but irreversible effects on Trx2 also suggest direct effects of acrolein. Prx1 (cytosolic) and Prx3 (mitochondrial) shifted to a largely oxidized state only when >90 and 100% of their respective Trxs were oxidized. Prx oxidation was readily reversed with a disulfide reductant, suggesting that Prx oxidation resulted from lack of reducing equivalents from Trx and not direct reaction with acrolein. The effects of acrolein on the thioredoxin system and

Contribution of PPARγ in modulation of acrolein-induced inflammatory signaling in gp91phox knock-out mice.

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Yousefipour, Zivar; Chug, Neha; Marek, Katarzyna; Nesbary, Alicia; Mathew, Joseph; Ranganna, Kasturi; Newaz, Mohammad A

2017-08-01

Oxidative stress and inflammation are major contributors to acrolein toxicity. Peroxisome proliferator activated receptor gamma (PPARγ) has antioxidant and anti-inflammatory effects. We investigated the contribution of PPARγ ligand GW1929 to the attenuation of oxidative stress in acrolein-induced insult. Male gp91 phox knock-out (KO) mice were treated with acrolein (0.5 mg·(kg body mass) -1 by intraperitoneal injection for 7 days) with or without GW1929 (GW; 0.5 mg·(kg body mass) -1 ·day -1 , orally, for 10 days). The livers were processed for further analyses. Acrolein significantly increased 8-isoprostane and reduced PPARγ activity (P acrolein-treated WT mice, and was reduced by GW1929 (by 65%). KO mice exhibited higher xanthine oxidase (XO). Acrolein increased XO and COX in WT mice and XO in KO mice. GW1929 significantly reduced COX in WT and KO mice and reduced XO in KO mice. Acrolein significantly reduced the total antioxidant status in WT and KO mice (P acrolein-treated WT mice. GW1929 reduced NF-κB levels (by 51%) in KO mice. Acrolein increased CD36 in KO mice (by 43%), which was blunted with GW1929. Data confirms that the generation of free radicals by acrolein is mainly through NAD(P)H, but other oxygenates play a role too. GW1929 may alleviate the toxicity of acrolein by attenuating NF-κB, COX, and CD36.

Glucose-stimulated acrolein production from unsaturated fatty acids.

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Medina-Navarro, R; Duran-Reyes, G; Diaz-Flores, M; Hicks, J J; Kumate, J

2004-02-01

Glucose auto-oxidation may be a significant source of reactive oxygen species (ROS), and also be important in the lipid peroxidation process, accompanied by the release of toxic reactive products. We wanted to demonstrate that acrolein can be formed directly and actively from free fatty acids in a hyperglycemic environment. A suspension of linoleic and arachidonic acids (2.5 mM) was exposed to different glucose concentrations (5, 10 and 15 mmol/L) in vitro. The samples were extracted with organic solvents, partitioned, followed at 255-267 nm, and analysed using capillary electrophoresis and mass spectroscopy. The total release of aldehydes significantly (P products, acrolein (5% of total) and its condensing product, 4-hydroxy-hexenal, were identified. From the results presented here, it was possible to demonstrate the production of acrolein, probably as a fatty acid product, due to free radicals generated from the glucose auto-oxidation process. The results led us to propose that acrolein, which is one of the most toxic aldehydes, is produced during hyperglycemic states, and may lead to tissue injury, as one of the initial problems to be linked to high levels of glucose in vivo.

Effects of acrolein on aldosterone release from zona glomerulosa cells in male rats.

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Wang, Kai-Lee; Huang, Wen-Ching; Chou, Jou-Chun; Weng, Ting-Chun; Hu, Sindy; Lieu, Fu-Kong; Lai, Wei-Ho; Idova, Galina; Wang, Paulus S; Wang, Shyi-Wu

2016-07-01

A positive correlation between smoking and hypertension has been well established. Acrolein is a major toxic volatile compound found in cigarette smoke. Human exposure to low levels of acrolein is unavoidable due to its production in daily activities, such as smoke from industrial, hot oil cooking vapors, and exhaust fumes from vehicles. The toxicity and the action mechanism of acrolein to induce apoptosis have been extensively studied, but the effects of acrolein on hypertension are still unknown. The present study aimed to examine the effects of acrolein on aldosterone release both in vivo and in vitro. Male rats were divided into three groups, and intraperitoneally injected with normal saline, or acrolein (2mg/kg) for 1 (group A-1) or 3 (group A-3) days, respectively. After sacrificing, rat blood samples were obtained to measure plasma aldosterone and angiotensin II (Ang II) levels. Zona glomerulosa (ZG) cells were prepared from rat adrenal cortex, and were incubated with or without stimulants. We found that the serum aldosterone was increased by 1.2-fold (pacrolein enhanced the stimulatory effects of Ang II and 8-bromo-cyclic AMP on aldosterone secretion from ZG cells prepared in both A-1 and A-3 groups. Furthermore, the enzyme activity of P450scc, the rate-limiting step of aldosterone synthesis, was elevated after acrolein injection. Plasma level of Ang II was increased in both A-1 and A-3 groups. These results suggested that acrolein exposure increased aldosterone production, at least in part, through elevating the level of plasma Ang II and stimulating steroidogenesis pathways. Copyright © 2016 Elsevier Inc. All rights reserved.

The formation of rats' choroidal neovascularization induced by acrolein

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Guan-Feng Wang

2016-04-01

Full Text Available AIM:To investigate the formation of rats' choroidal neovascularization(CNVinduced by acrolein. METHODS:Twelve Sprague-Dawley rats were randomly divided into three groups. Acrolein 200μL(2.5 mg/kg/dwas poured into the rats' stomach for 4wk as acrolein 4wk and for 8wk as acrolein 8wk group. The same volume of fresh water was also done to the rats as the control group. Remove all eye balls and embed into paraffin with HE staining.RESLUTS:The RPE-Bruch membrane was intact with no obvious abnormality in the control group and acrolein 4wk group. Lost in the continuity of RPE and the movement of choroidal neovascularization were found in the acrolein 8wk. CONCLUSION:The long time use of acrolein can induce the formation of choroial neovascularization in rats.

Acrolein decreases endothelial cell migration and insulin sensitivity through induction of let-7a.

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O'Toole, Timothy E; Abplanalp, Wesley; Li, Xiaohong; Cooper, Nigel; Conklin, Daniel J; Haberzettl, Petra; Bhatnagar, Aruni

2014-08-01

Acrolein is a major reactive component of vehicle exhaust, and cigarette and wood smoke. It is also present in several food substances and is generated endogenously during inflammation and lipid peroxidation. Although previous studies have shown that dietary or inhalation exposure to acrolein results in endothelial activation, platelet activation, and accelerated atherogenesis, the basis for these effects is unknown. Moreover, the effects of acrolein on microRNA (miRNA) have not been studied. Using AGILENT miRNA microarray high-throughput technology, we found that treatment of cultured human umbilical vein endothelial cells with acrolein led to a significant (>1.5-fold) upregulation of 12, and downregulation of 15, miRNAs. Among the miRNAs upregulated were members of the let-7 family and this upregulation was associated with decreased expression of their protein targets, β3 integrin, Cdc34, and K-Ras. Exposure to acrolein attenuated β3 integrin-dependent migration and reduced Akt phosphorylation in response to insulin. These effects of acrolein on endothelial cell migration and insulin signaling were reversed by expression of a let-7a inhibitor. Also, inhalation exposure of mice to acrolein (1 ppm x 6 h/day x 4 days) upregulated let-7a and led to a decrease in insulin-stimulated Akt phosphorylation in the aorta. These results suggest that acrolein exposure has broad effects on endothelial miRNA repertoire and that attenuation of endothelial cell migration and insulin signaling by acrolein is mediated in part by the upregulation of let-7a. This mechanism may be a significant feature of vascular injury caused by inflammation, oxidized lipids, and exposure to environmental pollutants. © The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Acrolein relaxes mouse isolated tracheal smooth muscle via a TRPA1-dependent mechanism.

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Cheah, Esther Y; Burcham, Philip C; Mann, Tracy S; Henry, Peter J

2014-05-01

Airway sensory C-fibres express TRPA1 channels which have recently been identified as a key chemosensory receptor for acrolein, a toxic and highly prevalent component of smoke. TRPA1 likely plays an intermediary role in eliciting a range of effects induced by acrolein including cough and neurogenic inflammation. Currently, it is not known whether acrolein-induced activation of TRPA1 produces other airway effects including relaxation of mouse airway smooth muscle. The aims of this study were to examine the effects of acrolein on airway smooth muscle tone in mouse isolated trachea, and to characterise the cellular and molecular mechanisms underpinning the effects of acrolein. Isometric tension recording studies were conducted on mouse isolated tracheal segments to characterise acrolein-induced relaxation responses. Release of the relaxant PGE₂ was measured by EIA to examine its role in the response. Use of selective antagonists/inhibitors permitted pharmacological characterisation of the molecular and cellular mechanisms underlying this relaxation response. Acrolein induced dose-dependent relaxation responses in mouse isolated tracheal segments. Importantly, these relaxation responses were significantly inhibited by the TRPA1 antagonists AP-18 and HC-030031, an NK₁ receptor antagonist RP-67580, and the EP₂ receptor antagonist PF-04418948, whilst completely abolished by the non-selective COX inhibitor indomethacin. Acrolein also caused rapid PGE₂ release which was suppressed by HC-030031. In summary, acrolein induced a novel bronchodilator response in mouse airways. Pharmacologic studies indicate that acrolein-induced relaxation likely involves interplay between TRPA1-expressing airway sensory C-fibres, NK₁ receptor-expressing epithelial cells, and EP₂-receptor expressing airway smooth muscle cells. Copyright © 2014 Elsevier Inc. All rights reserved.

Acrolein induces cyclooxygenase-2 and prostaglandin production in human umbilical vein endothelial cells: roles of p38 MAP kinase.

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Park, Yong Seek; Kim, Jayoung; Misonou, Yoshiko; Takamiya, Rina; Takahashi, Motoko; Freeman, Michael R; Taniguchi, Naoyuki

2007-06-01

Acrolein, a known toxin in tobacco smoke, might be involved in atherogenesis. This study examined the effect of acrolein on expression of cyclooxygenase-2 (COX-2) and prostaglandin (PG) production in endothelial cells. Cyclooxygenase (COX)-2 induction by acrolein and signal pathways were measured using Western blots, Northern blots, immunofluorescence, ELISA, gene silencing, and promoter assay. Colocalization of COX2 and acrolein-adduct was determined by immunohistochemistry. Here we report that the levels of COX-2 mRNA and protein are increased in human umbilical vein endothelial cells (HUVECs) after acrolein exposure. COX-2 was found to colocalize with acrolein-lysine adducts in human atherosclerotic lesions. Inhibition of p38 MAPK activity abolished the induction of COX-2 protein and PGE2 accumulation by acrolein, while suppression of extracellular signal-regulated kinase (ERK) and JNK activity had no effect on the induction of COX-2 expression in experiments using inhibitors and siRNA. Furthermore, rottlerin, an inhibitor of protein kinase Cdelta (PKCdelta), abrogated the upregulation of COX-2 at both protein and mRNA levels. These results provide that acrolein may play a role in progression of atherosclerosis and new information on the signaling pathways involved in COX-2 upregulation in response to acrolein and provide evidence that PKCdelta and p38 MAPK are required for transcriptional activation of COX-2.

Acrolein involvement in sensory and behavioral hypersensitivity following spinal cord injury in the rat.

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Due, Michael R; Park, Jonghyuck; Zheng, Lingxing; Walls, Michael; Allette, Yohance M; White, Fletcher A; Shi, Riyi

2014-03-01

Growing evidence suggests that oxidative stress, as associated with spinal cord injury (SCI), may play a critical role in both neuroinflammation and neuropathic pain conditions. The production of the endogenous aldehyde acrolein, following lipid peroxidation during the inflammatory response, may contribute to peripheral sensitization and hyperreflexia following SCI via the TRPA1-dependent mechanism. Here, we report that there are enhanced levels of acrolein and increased neuronal sensitivity to the aldehyde for at least 14 days after SCI. Concurrent with injury-induced increases in acrolein concentration is an increased expression of TRPA1 in the lumbar (L3-L6) sensory ganglia. As proof of the potential pronociceptive role for acrolein, intrathecal injections of acrolein revealed enhanced sensitivity to both tactile and thermal stimuli for up to 10 days, supporting the compound's pro-nociceptive functionality. Treatment of SCI animals with the acrolein scavenger hydralazine produced moderate improvement in tactile responses as well as robust changes in thermal sensitivity for up to 49 days. Taken together, these data suggest that acrolein directly modulates SCI-associated pain behavior, making it a novel therapeutic target for preclinical and clinical SCI as an analgesic. Following spinal cord injury (SCI), acrolein involvement in neuropathic pain is likely through direct activation and elevated levels of pro-nociceptive channel TRPA1. While acrolein elevation correlates with neuropathic pain, suppression of this aldehyde by hydralazine leads to an analgesic effect. Acrolein may serve as a novel therapeutic target for preclinical and clinical SCI to relieve both acute and chronic post-SCI neuropathic pain. © 2013 International Society for Neurochemistry.

Protein modification by acrolein: Formation and stability of cysteine adducts

OpenAIRE

Cai, Jian; Bhatnagar, Aruni; Pierce, William M.

2009-01-01

The toxicity of the ubiquitous pollutant and endogenous metabolite, acrolein, is due in part to covalent protein modifications. Acrolein reacts readily with protein nucleophiles via Michael addition and Schiff base formation. Potential acrolein targets in protein include the nucleophilic side chains of cysteine, histidine, and lysine residues as well as the free amino terminus of proteins. Although cysteine is the most acrolein-reactive residue, cysteine-acrolein adducts are difficult to iden...

Acrolein-mediated injury in nervous system trauma and diseases

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Shi, Riyi; Rickett, Todd; Sun, Wenjing

2012-01-01

Acrolein, an α,β-unsaturated aldehyde, is a ubiquitous pollutant that is also produced endogenously through lipid peroxidation. This compound is hundreds of times more reactive than other aldehydes such as 4-hydroxynonenal, is produced at much higher concentrations, and persists in solution for much longer than better known free radicals. It has been implicated in disease states known to involve chronic oxidative stress, particularly spinal cord injury and multiple sclerosis. Acrolein may overwhelm the anti-oxidative systems of any cell by depleting glutathione reserves, preventing glutathione regeneration, and inactivating protective enzymes. On the cellular level, acrolein exposure can cause membrane damage, mitochondrial dysfunction, and myelin disruption. Such pathologies can be exacerbated by increased concentrations or duration of exposure, and can occur in normal tissue incubated with injured spinal cord, showing that acrolein can act as a diffusive agent, spreading secondary injury. Several chemical species are capable of binding and inactivating acrolein. Hydralazine in particular can reduce acrolein concentrations and inhibit acrolein-mediated pathologies in vivo. Acrolein scavenging appears to be a novel effective treatment which is primed for rapid translation to the clinic. PMID:21823221

A model of hemorrhagic cystitis induced with acrolein in mice

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C.K.L.P. Batista

2006-11-01

Full Text Available Acrolein is a urinary metabolite of cyclophosphamide and ifosfamide, which has been reported to be the causative agent of hemorrhagic cystitis induced by these compounds. A direct cytotoxic effect of acrolein, however, has not yet been demonstrated. In the present study, the effects of intravesical injection of acrolein and mesna, the classical acrolein chemical inhibitor, were evaluated. Male Swiss mice weighing 25 to 35 g (N = 6 per group received saline or acrolein (25, 75, 225 µg intravesically 3, 6, 12, and 24 h before sacrifice for evaluation of bladder wet weight, macroscopic and histopathological changes by Gray's criteria, and 3 and 24 h for assessment of increase in vascular permeability. In other animals, mesna was administered intravesically (2 mg or systemically (80 mg/kg 1 h before acrolein. Intravesical administration of acrolein induced a dose- and time-dependent increase in vascular permeability and bladder wet weight (within 3 h: 2.2- and 21-fold increases in bladder wet weight and Evans blue dye exuded, respectively, at doses of 75 µg/bladder, as confirmed by Gray's criteria. Pretreatment with mesna (2-mercaptoethanesulfonic acid, which interacts with acrolein resulting in an inactive compound, inhibited all changes induced by acrolein. Our results are the first demonstration that intravesical administration of acrolein induces hemorrhagic cystitis. This model of acrolein-induced hemorrhagic cystitis in mice may be an important tool for the evaluation of the mechanism by which acrolein induces bladder lesion, as well as for investigation of new uroprotective drugs.

Intense correlation between brain infarction and protein-conjugated acrolein.

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Saiki, Ryotaro; Nishimura, Kazuhiro; Ishii, Itsuko; Omura, Tomohiro; Okuyama, Shigeru; Kashiwagi, Keiko; Igarashi, Kazuei

2009-10-01

We recently found that increases in plasma levels of protein-conjugated acrolein and polyamine oxidases, enzymes that produce acrolein, are good markers for stroke. The aim of this study was to determine whether the level of protein-conjugated acrolein is increased and levels of spermine and spermidine, the substrates of acrolein production, are decreased at the locus of infarction. A unilateral infarction was induced in mouse brain by photoinduction after injection of Rose Bengal. The volume of the infarction was analyzed using the public domain National Institutes of Health image program. The level of protein-conjugated acrolein at the locus of infarction and in plasma was measured by Western blotting and enzyme-linked immunosorbent assay, respectively. The levels of polyamines at the locus of infarction and in plasma were measured by high-performance liquid chromatography. The level of protein-conjugated acrolein was greatly increased, and levels of spermine and spermidine were decreased at the locus of infarction at 24 hours after the induction of stroke. The size of infarction was significantly decreased by N-acetylcysteine, a scavenger of acrolein. It was also found that the increases in the protein-conjugated acrolein, polyamines, and polyamine oxidases in plasma were observed after the induction of stroke. The results indicate that the induction of infarction is well correlated with the increase in protein-conjugated acrolein at the locus of infarction and in plasma.

Acrolein and Human Disease: Untangling the Knotty Exposure Scenarios Accompanying Several Diverse Disorders.

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Burcham, Philip C

2017-01-17

Acrolein is a highly toxic electrophile that participates in many diseases, yet efforts to delineate its precise mechanistic contributions to specific conditions are complicated by its wide distribution within human environments. This Perspective develops the proposal that due to its mixed status as environmental pollutant, metabolic byproduct, and endotoxicant which forms via ubiquitous pathophysiological processes, many diseases likely involve acrolein released from multiple sources. Although the category boundaries are indistinct, at least four identifiable exposure scenarios are identifiable. First, in some syndromes, such as those accompanying chronic or acute intoxication with smoke, whatever role acrolein plays in disease pathogenesis mainly traces to exogenous sources such as the combustion of tobacco or other organic matter. A second exposure category involves xenobiotics that undergo metabolism within the body to release acrolein. Still other health conditions, however, involve acrolein that forms via several endogenous pathways, some of which are activated upon intoxication with xenobiotics (i.e., Exposure Category 3), while still others accompany direct physical trauma to body tissues (Exposure Category 4). Further complicating efforts to clarify the role of endogenous acrolein in human disease is the likelihood that many such syndromes are complex phenomena that resemble "chemical mixture exposures" by involving multiple toxic substances simultaneously. This Perspective contends that while recent decades have witnessed much progress in describing the deleterious effects of acrolein at the cellular and molecular levels, more work is needed to define the contributions of different acrolein sources to "real-world" health conditions in human subjects.

Gut Microbial Glycerol Metabolism as an Endogenous Acrolein Source

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Jianbo Zhang

2018-01-01

Full Text Available Acrolein is a highly reactive electrophile causing toxic effects, such as DNA and protein adduction, oxidative stress, endoplasmic reticulum stress, immune dysfunction, and membrane damage. This Opinion/Hypothesis provides an overview of endogenous and exogenous acrolein sources, acrolein’s mode of action, and its metabolic fate. Recent reports underpin the finding that gut microbial glycerol metabolism leading to the formation of reuterin is an additional source of endogenous acrolein. Reuterin is an antimicrobial multicomponent system consisting of 3-hydroxypropionaldehyde, its dimer and hydrate, and also acrolein. The major conclusion is that gut microbes can metabolize glycerol to reuterin and that this transformation occurs in vivo. Given the known toxicity of acrolein, the observation that acrolein is formed in the gut necessitates further investigations on functional relevance for gut microbiota and the host.

Acrolein contributes to TRPA1 up-regulation in peripheral and central sensory hypersensitivity following spinal cord injury.

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Park, Jonghyuck; Zheng, Lingxing; Acosta, Glen; Vega-Alvarez, Sasha; Chen, Zhe; Muratori, Breanne; Cao, Peng; Shi, Riyi

2015-12-01

Acrolein, an endogenous aldehyde, has been shown to be involved in sensory hypersensitivity after rat spinal cord injury (SCI), for which the pathogenesis is unclear. Acrolein can directly activate a pro-algesic transient receptor protein ankyrin 1 (TRPA1) channel that exists in sensory neurons. Both acrolein and TRPA1 mRNA are elevated post SCI, which contributes to the activation of TRPA1 by acrolein and consequently, neuropathic pain. In the current study, we further showed that, post-SCI elevation of TRPA1 mRNA exists not only in dorsal root ganglias but also in both peripheral (paw skin) and central endings of primary afferent nerves (dorsal horn of spinal cord). This is the first indication that pain signaling can be over-amplified in the peripheral skin by elevated expressions of TRPA1 following SCI, in addition over-amplification previously seen in the spinal cord and dorsal root ganglia. Furthermore, we show that acrolein alone, in the absence of physical trauma, could lead to the elevation of TRPA1 mRNA at various locations when injected to the spinal cord. In addition, post-SCI elevation of TRPA1 mRNA could be mitigated using acrolein scavengers. Both of these attributes support the critical role of acrolein in elevating TRPA1 expression through gene regulation. Taken together, these data indicate that acrolein is likely a critical causal factor in heightening pain sensation post-SCI, through both the direct binding of TRPA1 receptor, and also by boosting the expression of TRPA1. Finally, our data also further support the notion that acrolein scavenging may be an effective therapeutic approach to alleviate neuropathic pain after SCI. We propose that the trauma-mediated elevation of acrolein causes neuropathic pain through at least two mechanisms: acrolein stimulates the production of transient receptor protein ankyrin 1 (TRPA1) in both central and peripheral locations, and it activates TRPA1 channels directly. Therefore, acrolein appears to be a critical

Chronic oral exposure to the aldehyde pollutant acrolein induces dilated cardiomyopathy

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Ismahil, Mohamed Ameen; Hamid, Tariq; Haberzettl, Petra; Gu, Yan; Chandrasekar, Bysani; Srivastava, Sanjay; Bhatnagar, Aruni

2011-01-01

Environmental triggers of dilated cardiomyopathy are poorly understood. Acute exposure to acrolein, a ubiquitous aldehyde pollutant, impairs cardiac function and cardioprotective responses in mice. Here, we tested the hypothesis that chronic oral exposure to acrolein induces inflammation and cardiomyopathy. C57BL/6 mice were gavage-fed acrolein (1 mg/kg) or water (vehicle) daily for 48 days. The dose was chosen based on estimates of human daily unsaturated aldehyde consumption. Compared with vehicle-fed mice, acrolein-fed mice exhibited significant (P acrolein adduct formation indicative of physical translocation of ingested acrolein to the heart. Acrolein also induced myocyte hypertrophy (∼2.2-fold increased myocyte area, P acrolein-exposed hearts, along with upregulated gene expression of proinflammatory cytokines tumor necrosis factor-α and interleukin-1β. Long-term oral exposure to acrolein, at an amount within the range of human unsaturated aldehyde intake, induces a phenotype of dilated cardiomyopathy in the mouse. Human exposure to acrolein may have analogous effects and raise consideration of an environmental, aldehyde-mediated basis for heart failure. PMID:21908791

Acrolein-Exposed Normal Human Lung Fibroblasts in Vitro: Cellular Senescence, Enhanced Telomere Erosion, and Degradation of Werner’s Syndrome Protein

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Jang, Jun-Ho; Bruse, Shannon; Huneidi, Salam; Schrader, Ronald M.; Monick, Martha M.; Lin, Yong; Carter, A. Brent; Klingelhutz, Aloysius J.

2014-01-01

Background: Acrolein is a ubiquitous environmental hazard to human health. Acrolein has been reported to activate the DNA damage response and induce apoptosis. However, little is known about the effects of acrolein on cellular senescence. Objectives: We examined whether acrolein induces cellular senescence in cultured normal human lung fibroblasts (NHLF). Methods: We cultured NHLF in the presence or absence of acrolein and determined the effects of acrolein on cell proliferative capacity, senescence-associated β-galactosidase activity, the known senescence-inducing pathways (e.g., p53, p21), and telomere length. Results: We found that acrolein induced cellular senescence by increasing both p53 and p21. The knockdown of p53 mediated by small interfering RNA (siRNA) attenuated acrolein-induced cellular senescence. Acrolein decreased Werner’s syndrome protein (WRN), a member of the RecQ helicase family involved in DNA repair and telomere maintenance. Acrolein-induced down-regulation of WRN protein was rescued by p53 knockdown or proteasome inhibition. Finally, we found that acrolein accelerated p53-mediated telomere shortening. Conclusions: These results suggest that acrolein induces p53-mediated cellular senescence accompanied by enhanced telomere attrition and WRN protein down-regulation. Citation: Jang JH, Bruse S, Huneidi S, Schrader RM, Monick MM, Lin Y, Carter AB, Klingelhutz AJ, Nyunoya T. 2014. Acrolein-exposed normal human lung fibroblasts in vitro: cellular senescence, enhanced telomere erosion, and degradation of Werner’s syndrome protein. Environ Health Perspect 122:955–962; http://dx.doi.org/10.1289/ehp.1306911 PMID:24747221

Proteomic analysis of rat cerebral cortex following subchronic acrolein toxicity

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Rashedinia, Marzieh; Lari, Parisa [Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad (Iran, Islamic Republic of); Abnous, Khalil, E-mail: Abnouskh@mums.ac.r [Pharmaceutical Research Center, Department of Medicinal Chemistry, Mashhad University of Medical Sciences, Mashhad (Iran, Islamic Republic of); Hosseinzadeh, Hossein, E-mail: Hosseinzadehh@mums.ac.ir [Pharmaceutical Research Center, Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad (Iran, Islamic Republic of)

2013-10-01

Acrolein, a member of reactive α,β-unsaturated aldehydes, is a major environmental pollutant. Acrolein is also produced endogenously as a toxic by-product of lipid peroxidation. Because of high reactivity, acrolein may mediate oxidative damages to cells and tissues. It has been shown to be involved in a wide variety of pathological states including pulmonary, atherosclerosis and neurodegenerative diseases. In this study we employed proteomics approach to investigate the effects of subchronic oral exposures to 3 mg/kg of acrolein on protein expression profile in the brain of rats. Moreover effects of acrolein on malondialdehyde (MDA) levels and reduced glutathione (GSH) content were investigated. Our results revealed that treatment with acrolein changed levels of several proteins in diverse physiological process including energy metabolism, cell communication and transport, response to stimulus and metabolic process. Interestingly, several differentially over-expressed proteins, including β-synuclein, enolase and calcineurin, are known to be associated with human neurodegenerative diseases. Changes in the levels of some proteins were confirmed by Western blot. Moreover, acrolein increases the level of MDA, as a lipid peroxidation biomarker and decreased GSH concentrations, as a non-enzyme antioxidant in the brain of acrolein treated rats. These findings suggested that acrolein induces the oxidative stress and lipid peroxidation in the brain, and so that may contribute to the pathophysiology of neurological disorders. - Highlights: • Acrolein intoxication increased lipid peroxidation and deplete GSH in rat brain. • Effect of acrolein on protein levels of cerebral cortex was analyzed by 2DE-PAGE. • Levels of a number of proteins with different biological functions were increased.

Proteomic analysis of rat cerebral cortex following subchronic acrolein toxicity

International Nuclear Information System (INIS)

Rashedinia, Marzieh; Lari, Parisa; Abnous, Khalil; Hosseinzadeh, Hossein

2013-01-01

Acrolein, a member of reactive α,β-unsaturated aldehydes, is a major environmental pollutant. Acrolein is also produced endogenously as a toxic by-product of lipid peroxidation. Because of high reactivity, acrolein may mediate oxidative damages to cells and tissues. It has been shown to be involved in a wide variety of pathological states including pulmonary, atherosclerosis and neurodegenerative diseases. In this study we employed proteomics approach to investigate the effects of subchronic oral exposures to 3 mg/kg of acrolein on protein expression profile in the brain of rats. Moreover effects of acrolein on malondialdehyde (MDA) levels and reduced glutathione (GSH) content were investigated. Our results revealed that treatment with acrolein changed levels of several proteins in diverse physiological process including energy metabolism, cell communication and transport, response to stimulus and metabolic process. Interestingly, several differentially over-expressed proteins, including β-synuclein, enolase and calcineurin, are known to be associated with human neurodegenerative diseases. Changes in the levels of some proteins were confirmed by Western blot. Moreover, acrolein increases the level of MDA, as a lipid peroxidation biomarker and decreased GSH concentrations, as a non-enzyme antioxidant in the brain of acrolein treated rats. These findings suggested that acrolein induces the oxidative stress and lipid peroxidation in the brain, and so that may contribute to the pathophysiology of neurological disorders. - Highlights: • Acrolein intoxication increased lipid peroxidation and deplete GSH in rat brain. • Effect of acrolein on protein levels of cerebral cortex was analyzed by 2DE-PAGE. • Levels of a number of proteins with different biological functions were increased

Acrolein inhalation suppresses lipopolysaccharide-induced inflammatory cytokine production but does not affect acute airways neutrophilia.

Science.gov (United States)

Kasahara, David Itiro; Poynter, Matthew E; Othman, Ziryan; Hemenway, David; van der Vliet, Albert

2008-07-01

Acrolein is a reactive unsaturated aldehyde that is produced during endogenous oxidative processes and is a major bioactive component of environmental pollutants such as cigarette smoke. Because in vitro studies demonstrate that acrolein can inhibit neutrophil apoptosis, we evaluated the effects of in vivo acrolein exposure on acute lung inflammation induced by LPS. Male C57BL/6J mice received 300 microg/kg intratracheal LPS and were exposed to acrolein (5 parts per million, 6 h/day), either before or after LPS challenge. Exposure to acrolein either before or after LPS challenge did not significantly affect the overall extent of LPS-induced lung inflammation, or the duration of the inflammatory response, as observed from recovered lung lavage leukocytes and histology. However, exposure to acrolein after LPS instillation markedly diminished the LPS-induced production of several inflammatory cytokines, specifically TNF-alpha, IL-12, and the Th1 cytokine IFN-gamma, which was associated with reduction in NF-kappaB activation. Our data demonstrate that acrolein exposure suppresses LPS-induced Th1 cytokine responses without affecting acute neutrophilia. Disruption of cytokine signaling by acrolein may represent a mechanism by which smoking contributes to chronic disease in chronic obstructive pulmonary disease and asthma.

Increase in acrolein-conjugated immunoglobulins in saliva from patients with primary Sjögren's syndrome.

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Hirose, Tadao; Saiki, Ryotaro; Uemura, Takeshi; Suzuki, Takehiro; Dohmae, Naoshi; Ito, Satoshi; Takahashi, Hoyu; Ishii, Itsuko; Toida, Toshihiko; Kashiwagi, Keiko; Igarashi, Kazuei

2015-10-23

We previously reported that the level of protein-conjugated acrolein (PC-Acro), a marker of cell or tissue damage, was increased in saliva from patients with primary Sjögren's syndrome (pSS), and that the level of PC-Acro was well correlated with the severity of pSS. Acrolein-conjugated immunoglobulins were measured in saliva from pSS patients. The activities of autoantibodies recognizing Sjögren's syndrome SSA (Ro) and SSB (La) proteins in saliva from pSS patients were approximately 3- to 5-fold higher than those from control subjects. We also found that autoantibody activities recognizing SSA (Ro) and SSB (La) proteins increased after acrolein treatment of saliva from control subjects. When an antibody against human serum albumin was treated with acrolein, the ability to recognize albumin was reduced but the ability to recognize other proteins was increased. Twenty-four and eleven kinds of acrolein-conjugated amino acids were found at the variable and constant regions of peptides, respectively, obtained from the immunoglobulins in saliva from pSS patients. The altered recognition patterns of immunoglobulins due to acrolein conjugation are at least partially involved in autoimmune diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

Role of TRPA1 in acute cardiopulmonary toxicity of inhaled acrolein

International Nuclear Information System (INIS)

Conklin, Daniel J.; Haberzettl, Petra; Jagatheesan, Ganapathy; Kong, Maiying; Hoyle, Gary W.

2017-01-01

Acrolein is a highly toxic, volatile, unsaturated aldehyde generated during incomplete combustion as in tobacco smoke and indoor fires. Because the transient receptor potential ankyrin 1 (TRPA1) channel mediates tobacco smoke-induced lung injury, we assessed its role in high-level acrolein-induced toxicity in mice. Acrolein (100–275 ppm, 10–30 min) caused upper airway epithelial sloughing, bradypnea and oral gasping, hypothermia, cardiac depression and mortality. Male wild-type mice (WT, C57BL/6; 5–52 weeks) were significantly more sensitive to high-level acrolein than age-matched, female WT mice. Both male and female TRPA1-null mice were more sensitive to acrolein-induced mortality than age- and sex-matched WT mice. Acrolein exposure increased lung weight:body weight ratios and lung albumin and decreased plasma albumin to a greater extent in TRPA1-null than in WT mice. Lung and plasma protein-acrolein adducts were not increased in acrolein-exposed TRPA1-null mice compared with WT mice. To assess TRPA1-dependent protective mechanisms, respiratory parameters were monitored by telemetry. TRPA1-null mice had a slower onset of breathing rate suppression (‘respiratory braking’) than WT mice suggesting TRPA1 mediates this protective response. Surprisingly, WT male mice treated either with a TRPA1 antagonist (HC030031; 200 mg/kg) alone or with combined TRPA1 (100 mg/kg) and TRPV1 (capsazepine, 10 mg/kg) antagonists at 30 min post-acrolein exposure (i.e., “real world” delay in treatment) were significantly protected from acrolein-induced mortality. These data show TRPA1 protects against high-level acrolein-induced toxicity in a sex-dependent manner. Post-exposure TRPA1 antagonism also protected against acrolein-induced mortality attesting to a complex role of TRPA1 in cardiopulmonary injury. - Highlights: • TRPA1 protects mice against toxicity and mortality of inhaled high-level acrolein. • TRPA1 protection against inhaled high-level acrolein is sex

Role of TRPA1 in acute cardiopulmonary toxicity of inhaled acrolein

Energy Technology Data Exchange (ETDEWEB)

Conklin, Daniel J., E-mail: dj.conklin@louisville.edu [Diabetes and Obesity Center, Institute of Molecular Cardiology, Division of Cardiovascular Medicine, Department of Medicine, School of Medicine, University of Louisville, Louisville, KY 40292 (United States); Haberzettl, Petra; Jagatheesan, Ganapathy [Diabetes and Obesity Center, Institute of Molecular Cardiology, Division of Cardiovascular Medicine, Department of Medicine, School of Medicine, University of Louisville, Louisville, KY 40292 (United States); Kong, Maiying [Department of Bioinformatics and Biostatistics, School of Public Health & Information Sciences, University of Louisville, Louisville, KY 40292 (United States); Hoyle, Gary W. [Department of Environmental and Occupational Health Sciences, School of Public Health & Information Sciences, University of Louisville, Louisville, KY 40292 (United States)

2017-06-01

Acrolein is a highly toxic, volatile, unsaturated aldehyde generated during incomplete combustion as in tobacco smoke and indoor fires. Because the transient receptor potential ankyrin 1 (TRPA1) channel mediates tobacco smoke-induced lung injury, we assessed its role in high-level acrolein-induced toxicity in mice. Acrolein (100–275 ppm, 10–30 min) caused upper airway epithelial sloughing, bradypnea and oral gasping, hypothermia, cardiac depression and mortality. Male wild-type mice (WT, C57BL/6; 5–52 weeks) were significantly more sensitive to high-level acrolein than age-matched, female WT mice. Both male and female TRPA1-null mice were more sensitive to acrolein-induced mortality than age- and sex-matched WT mice. Acrolein exposure increased lung weight:body weight ratios and lung albumin and decreased plasma albumin to a greater extent in TRPA1-null than in WT mice. Lung and plasma protein-acrolein adducts were not increased in acrolein-exposed TRPA1-null mice compared with WT mice. To assess TRPA1-dependent protective mechanisms, respiratory parameters were monitored by telemetry. TRPA1-null mice had a slower onset of breathing rate suppression (‘respiratory braking’) than WT mice suggesting TRPA1 mediates this protective response. Surprisingly, WT male mice treated either with a TRPA1 antagonist (HC030031; 200 mg/kg) alone or with combined TRPA1 (100 mg/kg) and TRPV1 (capsazepine, 10 mg/kg) antagonists at 30 min post-acrolein exposure (i.e., “real world” delay in treatment) were significantly protected from acrolein-induced mortality. These data show TRPA1 protects against high-level acrolein-induced toxicity in a sex-dependent manner. Post-exposure TRPA1 antagonism also protected against acrolein-induced mortality attesting to a complex role of TRPA1 in cardiopulmonary injury. - Highlights: • TRPA1 protects mice against toxicity and mortality of inhaled high-level acrolein. • TRPA1 protection against inhaled high-level acrolein is sex

Update of the exploratory report Acrolein

NARCIS (Netherlands)

Slooff W; Bont PFH; Janus JA; Pronk MEJ; Ros JPM; ECO; PPCbv; ACT; LAE

1994-01-01

The report is an update of the exploratory report acrolein (Slooff et al., 1991) that served as a basis for the discussion during the exploratory meeting on acrolein in March 1992. The meeting supported the conclusion that priority should be given to the compartment air and to the risks to humans.

The Relationship Between Structural and Catalytic Activity of α and γ-Bismuth-Molybdate Catalysts for Partial Oxidation of Propylene to Acrolein

Science.gov (United States)

Fansuri, H.; Pham, G. H.; Wibawanta, S.; Zhang, D. K.; French, David

Bismuth-molybdate catalysts are known to be effective for catalytic partial oxidation of propylene to acrolein. Their properties and the kinetics and reaction mechanisms for acrolein production have been extensively studied, especially in their basic forms, such as α, β, and γ-bismuth-molybdate. Although the reaction mechanisms have been reported widely in the literature, a general agreement has not been reached, especially from a catalyst-structure point of view. The present contribution reports an effort to understand the structural changes of α and γ-bismuth-molybdate catalysts at varying temperatures as examined using high temperature XRD and to relate the catalyst performance (activity and selectivity) for propylene partial oxidation to acrolein. The XRD analysis was performed at temperature between 250 and 450°C in ambient atmosphere and the Rietveld refinement method was used to extract unit cell parameters. The results showed a distinct similarity between the shapes of the thermal expansion of the catalysts and their activity and selectivity curves, indicating a significant role that the catalyst interatomic structure plays in the overall reaction mechanism.

ORAL EXPOSURE TO ACROLEIN EXACERBATES ATHEROSCLEROSIS IN APO E-NULL MICE

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Srivastava, Sanjay; Sithu, Srinivas D.; Vladykovskaya, Elena; Haberzettl, Petra; Hoetker, David J.; Siddiqui, Maqsood A.; Conklin, Daniel J.; D'Souza, Stanley E.; Bhatnagar, Aruni

2011-01-01

Background Acrolein is a dietary aldehyde that is present in high concentrations in alcoholic beverages and foods including cheese, donuts and coffee. It is also abundant in tobacco smoke, automobile exhaust and industrial waste and is generated in vivo during inflammation and oxidative stress. Objectives The goal of this study was to examine the effects of dietary acrolein on atherosclerosis. Methods Eight-week old male apoE-null mice were gavage-fed acrolein (2.5 mg/kg/day) for 8 weeks. Atherosclerotic lesion formation and composition and plasma lipids and platelet factor 4 (PF4) levels were measured. Effects of acrolein and PF4 on endothelial cell function was measured in vitro. Results Acrolein feeding increased the concentration of cholesterol in the plasma. NMR analysis of the lipoproteins showed that acrolein feeding increased the abundance of small and medium VLDL particles. Acrolein feeding also increased atherosclerotic lesion formation in the aortic valve and the aortic arch. Immunohistochemical analysis showed increased macrophage accumulation in the lesions of acrolein-fed mice. Plasma PF4 levels and accumulation of PF4 in atherosclerotic lesions was increased in the acrolein-fed mice. Incubation of endothelial cells with the plasma of acrolein-fed mice augmented transmigration of monocytic cells, which was abolished by anti-PF4 antibody treatment. Conclusions Dietary exposure to acrolein exacerbates atherosclerosis in apoE-null mice. Consumption of foods and beverages rich in unsaturated aldehydes such as acrolein may be a contributing factor to the progression of atherosclerotic lesions. PMID:21371710

Proteomic analysis of rat cerebral cortex following subchronic acrolein toxicity.

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Rashedinia, Marzieh; Lari, Parisa; Abnous, Khalil; Hosseinzadeh, Hossein

2013-10-01

Acrolein, a member of reactive α,β-unsaturated aldehydes, is a major environmental pollutant. Acrolein is also produced endogenously as a toxic by-product of lipid peroxidation. Because of high reactivity, acrolein may mediate oxidative damages to cells and tissues. It has been shown to be involved in a wide variety of pathological states including pulmonary, atherosclerosis and neurodegenerative diseases. In this study we employed proteomics approach to investigate the effects of subchronic oral exposures to 3mg/kg of acrolein on protein expression profile in the brain of rats. Moreover effects of acrolein on malondialdehyde (MDA) levels and reduced glutathione (GSH) content were investigated. Our results revealed that treatment with acrolein changed levels of several proteins in diverse physiological process including energy metabolism, cell communication and transport, response to stimulus and metabolic process. Interestingly, several differentially over-expressed proteins, including β-synuclein, enolase and calcineurin, are known to be associated with human neurodegenerative diseases. Changes in the levels of some proteins were confirmed by Western blot. Moreover, acrolein increases the level of MDA, as a lipid peroxidation biomarker and decreased GSH concentrations, as a non-enzyme antioxidant in the brain of acrolein treated rats. These findings suggested that acrolein induces the oxidative stress and lipid peroxidation in the brain, and so that may contribute to the pathophysiology of neurological disorders. Copyright © 2013 Elsevier Inc. All rights reserved.

IRIS Toxicological Review of Acrolein (2003 Final)

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EPA announced the release of the final report, Toxicological Review of Acrolein: in support of the Integrated Risk Information System (IRIS). The updated Summary for Acrolein and accompanying toxicological review have been added to the IRIS Database.

The Tobacco Smoke Component, Acrolein, Suppresses Innate Macrophage Responses by Direct Alkylation of c-Jun N-Terminal Kinase

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Hristova, Milena; Spiess, Page C.; Kasahara, David I.; Randall, Matthew J.; Deng, Bin

2012-01-01

The respiratory innate immune system is often compromised by tobacco smoke exposure, and previous studies have indicated that acrolein, a reactive electrophile in tobacco smoke, may contribute to the immunosuppressive effects of smoking. Exposure of mice to acrolein at concentrations similar to those in cigarette smoke (5 ppm, 4 h) significantly suppressed alveolar macrophage responses to bacterial LPS, indicated by reduced induction of nitric oxide synthase 2, TNF-α, and IL-12p40. Mechanistic studies with bone marrow–derived macrophages or MH-S macrophages demonstrated that acrolein (1–30 μM) attenuated these LPS-mediated innate responses in association with depletion of cellular glutathione, although glutathione depletion itself was not fully responsible for these immunosuppressive effects. Inhibitory actions of acrolein were most prominent after acute exposure (acrolein with critical signaling pathways. Among the key signaling pathways involved in innate macrophage responses, acrolein marginally affected LPS-mediated activation of nuclear factor (NF)-κB, and significantly suppressed phosphorylation of c-Jun N-terminal kinase (JNK) and activation of c-Jun. Using biotin hydrazide labeling, NF-κB RelA and p50, as well as JNK2, a critical mediator of innate macrophage responses, were revealed as direct targets for alkylation by acrolein. Mass spectrometry analysis of acrolein-modified recombinant JNK2 indicated adduction to Cys41 and Cys177, putative important sites involved in mitogen-activated protein kinase (MAPK) kinase (MEK) binding and JNK2 phosphorylation. Our findings indicate that direct alkylation of JNK2 by electrophiles, such as acrolein, may be a prominent and hitherto unrecognized mechanism in their immunosuppressive effects, and may be a major factor in smoking-induced effects on the immune system. PMID:21778411

Acrolein: An Effective Biomarker for Tissue Damage Produced from Polyamines.

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Igarashi, Kazuei; Uemura, Takeshi; Kashiwagi, Keiko

2018-01-01

It is thought that the major factor responsible for cell damage is reactive oxygen species (ROS), but our recent studies have shown that acrolein (CH 2 =CH-CHO) produced from spermine and spermidine is more toxic than ROS. Thus, (1) the mechanism of acrolein production during brain stroke, (2) one of the mechanisms of acrolein toxicity, and (3) the role of glutathione in acrolein detoxification are described in this chapter.

Acrolein and thiol-reactive electrophiles suppress allergen-induced innate airway epithelial responses by inhibition of DUOX1 and EGFR.

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Danyal, Karamatullah; de Jong, Willem; O'Brien, Edmund; Bauer, Robert A; Heppner, David E; Little, Andrew C; Hristova, Milena; Habibovic, Aida; van der Vliet, Albert

2016-11-01

Acrolein is a major thiol-reactive component of cigarette smoke (CS) that is thought to contribute to increased asthma incidence associated with smoking. Here, we explored the effects of acute acrolein exposure on innate airway responses to two common airborne allergens, house dust mite and Alternaria alternata, and observed that acrolein exposure of C57BL/6 mice (5 ppm, 4 h) dramatically inhibited innate airway responses to subsequent allergen challenge, demonstrated by attenuated release of the epithelial-derived cytokines IL-33, IL-25, and IL-1α. Acrolein and other anti-inflammatory thiol-reactive electrophiles, cinnamaldehyde, curcumin, and sulforaphane, similarly inhibited allergen-induced production of these cytokines from human or murine airway epithelial cells in vitro. Based on our previous observations indicating the importance of Ca 2+ -dependent signaling, activation of the NADPH oxidase DUOX1, and Src/EGFR-dependent signaling in allergen-induced epithelial secretion of these cytokines, we explored the impact of acrolein on these pathways. Acrolein and other thiol-reactive electrophiles were found to dramatically prevent allergen-induced activation of DUOX1 as well as EGFR, and acrolein was capable of inhibiting EGFR tyrosine kinase activity via modification of C797. Biotin-labeling strategies indicated increased cysteine modification and carbonylation of Src, EGFR, as well as DUOX1, in response to acrolein exposure in vitro and in vivo, suggesting that direct alkylation of these proteins on accessible cysteine residues may be responsible for their inhibition. Collectively, our findings indicate a novel anti-inflammatory mechanism of CS-derived acrolein and other thiol-reactive electrophiles, by directly inhibiting DUOX1- and EGFR-mediated airway epithelial responses to airborne allergens. Copyright © 2016 the American Physiological Society.

Acrolein inhalation alters arterial blood gases and triggers carotid body-mediated cardiovascular responses in hypertensive rats.

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Perez, Christina M; Hazari, Mehdi S; Ledbetter, Allen D; Haykal-Coates, Najwa; Carll, Alex P; Cascio, Wayne E; Winsett, Darrell W; Costa, Daniel L; Farraj, Aimen K

2015-01-01

Air pollution exposure affects autonomic function, heart rate, blood pressure and left ventricular function. While the mechanism for these effects is uncertain, several studies have reported that air pollution exposure modifies activity of the carotid body, the major organ that senses changes in arterial oxygen and carbon dioxide levels, and elicits downstream changes in autonomic control and cardiac function. We hypothesized that exposure to acrolein, an unsaturated aldehyde and mucosal irritant found in cigarette smoke and diesel exhaust, would activate the carotid body chemoreceptor response and lead to secondary cardiovascular responses in rats. Spontaneously hypertensive (SH) rats were exposed once for 3 h to 3 ppm acrolein gas or filtered air in whole body plethysmograph chambers. To determine if the carotid body mediated acrolein-induced cardiovascular responses, rats were pretreated with an inhibitor of cystathionine γ-lyase (CSE), an enzyme essential for carotid body signal transduction. Acrolein exposure induced several cardiovascular effects. Systolic, diastolic and mean arterial blood pressure increased during exposure, while cardiac contractility decreased 1 day after exposure. The cardiovascular effects were associated with decreases in pO2, breathing frequency and expiratory time, and increases in sympathetic tone during exposure followed by parasympathetic dominance after exposure. The CSE inhibitor prevented the cardiovascular effects of acrolein exposure. Pretreatment with the CSE inhibitor prevented the cardiovascular effects of acrolein, suggesting that the cardiovascular responses with acrolein may be mediated by carotid body-triggered changes in autonomic tone. (This abstract does not reflect EPA policy.).

Role of TRPA1 in acute cardiopulmonary toxicity of inhaled acrolein.

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Conklin, Daniel J; Haberzettl, Petra; Jagatheesan, Ganapathy; Kong, Maiying; Hoyle, Gary W

2017-06-01

Acrolein is a highly toxic, volatile, unsaturated aldehyde generated during incomplete combustion as in tobacco smoke and indoor fires. Because the transient receptor potential ankyrin 1 (TRPA1) channel mediates tobacco smoke-induced lung injury, we assessed its role in high-level acrolein-induced toxicity in mice. Acrolein (100-275ppm, 10-30min) caused upper airway epithelial sloughing, bradypnea and oral gasping, hypothermia, cardiac depression and mortality. Male wild-type mice (WT, C57BL/6; 5-52weeks) were significantly more sensitive to high-level acrolein than age-matched, female WT mice. Both male and female TRPA1-null mice were more sensitive to acrolein-induced mortality than age- and sex-matched WT mice. Acrolein exposure increased lung weight:body weight ratios and lung albumin and decreased plasma albumin to a greater extent in TRPA1-null than in WT mice. Lung and plasma protein-acrolein adducts were not increased in acrolein-exposed TRPA1-null mice compared with WT mice. To assess TRPA1-dependent protective mechanisms, respiratory parameters were monitored by telemetry. TRPA1-null mice had a slower onset of breathing rate suppression ('respiratory braking') than WT mice suggesting TRPA1 mediates this protective response. Surprisingly, WT male mice treated either with a TRPA1 antagonist (HC030031; 200mg/kg) alone or with combined TRPA1 (100mg/kg) and TRPV1 (capsazepine, 10mg/kg) antagonists at 30min post-acrolein exposure (i.e., "real world" delay in treatment) were significantly protected from acrolein-induced mortality. These data show TRPA1 protects against high-level acrolein-induced toxicity in a sex-dependent manner. Post-exposure TRPA1 antagonism also protected against acrolein-induced mortality attesting to a complex role of TRPA1 in cardiopulmonary injury. Copyright © 2016 Elsevier Inc. All rights reserved.

Liposomal inhibition of acrolein-induced injury in rat cultured urothelial cells.

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Nirmal, J; Wolf-Johnston, A S; Chancellor, M B; Tyagi, P; Anthony, M; Kaufman, J; Birder, L A

2014-10-01

To study the protection offered by empty liposomes (LPs) alone against acrolein-induced changes in urothelial cell viability and explored uptake of LPs by primary (rat) urothelial cells. Acrolein was used as a means to induce cellular damage and reduce urothelial cellular viability. The effect of acrolein or liposomal treatment on cellular proliferation was studied using 5-bromo-2'-deoxy-uridine assay. Cytokine release was measured after urothelial cells were exposed to acrolein. Temperature-dependent uptake study was carried out for fluorescent-labeled LPs using confocal microscopy. Liposome pretreatment protected against acrolein-induced decrease in urothelial cell proliferation. LPs also significantly affected the acrolein-induced cytokine (interferon-gamma) release offering protection to the urothelial cells against acrolein damage. We also observed a temperature-dependent urothelial uptake of fluorescent-labeled LPs occurred at 37 °C (but not at 4 °C). Empty LPs alone provide a therapeutic efficacy against acrolein-induced changes in urothelial cell viability and may be a promising local therapy for bladder diseases. Hence, our preliminary evidence provides support for liposome-therapy for urothelial protection and possible repair.

Melatonin suppresses acrolein-induced IL-8 production in human pulmonary fibroblasts.

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Kim, Gun-Dong; Lee, Seung Eun; Kim, Tae-Ho; Jin, Young-Ho; Park, Yong Seek; Park, Cheung-Seog

2012-04-01

Cigarette smoke (CS) causes harmful alterations in the lungs and airway structures and functions that characterize chronic obstructive pulmonary disease (COPD). In addition to COPD, active cigarette smoking causes other respiratory diseases and diminishes health status. Furthermore, recent studies show that, α, β-unsaturated aldehyde acrolein in CS induces the production of interleukin (IL)-8, which is known to be related to bronchitis, rhinitis, pulmonary fibrosis, and asthma. In addition, lung and pulmonary fibroblasts secrete IL-8, which has a chemotactic effect on leukocytes, and which in turn, play a critical role in lung inflammation. On the other hand, melatonin regulates circadian rhythm homeostasis in humans and has many other effects, which include antioxidant and anti-inflammatory effects, as demonstrated by the reduced expressions of iNOS, IL-1β, and IL-6 and increased glutathione (GSH) and superoxide dismutase activities. In this study, we investigated whether melatonin suppresses acrolein-induced IL-8 secretion in human pulmonary fibroblasts (HPFs). It was found that acrolein-induced IL-8 production was accompanied by increased levels of phosphorylation of Akt and extracellular signal-regulated kinases (ERK1/2) in HPFs, and that melatonin suppressed IL-8 production in HPFs. These results suggest that melatonin suppresses acrolein-induced IL-8 production via ERK1/2 and phosphatidylinositol 3-kinase (PI3K)/Akt signal inhibition in HPFs. © 2011 John Wiley & Sons A/S.

Acute effects of acrolein in human volunteers during controlled exposure.

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Dwivedi, Aishwarya M; Johanson, Gunnar; Lorentzen, Johnny C; Palmberg, Lena; Sjögren, Bengt; Ernstgård, Lena

2015-01-01

Acrolein is a reactive aldehyde mainly formed by combustion. The critical effect is considered to be irritation of the eyes and airways; however, the scarce data available make it difficult to assess effect levels. The aim of the study was to determine thresholds for acute irritation for acrolein. Nine healthy volunteers of each sex were exposed at six occasions for 2 h at rest to: clean air, 15 ppm ethyl acetate (EA), and 0.05 ppm and 0.1 ppm acrolein with and without EA (15 ppm) to mask the potential influence of odor. Symptoms related to irritation and central nervous system effects were rated on 100-mm Visual Analogue Scales. The ratings of eye irritation were slightly but significantly increased during exposure to acrolein in a dose-dependent manner (p acrolein alone but not during any of the other five exposure conditions. Based on subjective ratings, the present study showed minor eye irritation by exposure to 0.1 ppm acrolein.

OPTIMIZING THE PAKS METHOD FOR MEASURING AIRBORNE ACROLEIN

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Airborne acrolein is produced from the combustion of fuel and tobacco and is of concern due to its potential for respiratory tract irritation and other adverse health effects. DNPH active-sampling is a method widely used for sampling airborne aldehydes and ketones (carbonyls); ...

Anticancer system created by acrolein and hydroxyl radical generated in enzymatic oxidation of spermine and other biochemical reactions.

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Alarcon, R A

2012-10-01

A hypothesis suggesting the existence of a ubiquitous physiological anticancer system created by two highly reactive oxidative stress inducers with anticancer properties, acrolein and hydroxyl radical, is reported in this communication. Both components can originate separately or together in several biochemical interactions, among them, the enzymatic oxidation of the polyamine spermine, which appear to be their main source. The foundations of this hypothesis encompass our initial search for growth-inhibitors or anticancer compounds in biological material leading to the isolation of spermine, a polyamine that became highly cytotoxic through the generation of acrolein, when enzymatically oxidized. Findings complemented with pertinent literature data by other workers and observed anticancer activities by sources capable of producing acrolein and hydroxyl radical. This hypothesis obvious implication: spermine enzymatic oxidations or other biochemical interactions that would co-generate acrolein and hydroxyl radical, the anticancer system components, should be tried as treatments for any given cancer. The biochemical generation of acrolein observed was totally unexpected, since this aldehyde was known; as a very toxic and highly reactive xenobiotic chemical produced in the pyrolysis of fats and other organic material, found as an atmospheric pollutant, in tobacco smoke and car emissions, and mainly used as a pesticide or aquatic herbicide. Numerous studies on acrolein, considered after our work a biological product, as well, followed. In them, acrolein widespread presence, its effects on diverse cellular proteins, such as, growth factors, and its anticancer activities, were additionally reported. Regarding hydroxyl radical, the second component of the proposed anticancer system, and another cytotoxic product in normal cell metabolism, it co-generates with acrolein in several biochemical interactions, occurrences suggesting that these products might jointly fulfill some

Nonredundant functions of alphabeta and gammadelta T cells in acrolein-induced pulmonary pathology.

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Borchers, Michael T; Wesselkamper, Scott C; Eppert, Bryan L; Motz, Gregory T; Sartor, Maureen A; Tomlinson, Craig R; Medvedovic, Mario; Tichelaar, Jay W

2008-09-01

Acrolein exposure represents a significant human health hazard. Repeated acrolein exposure causes the accumulation of monocytes/macrophages and lymphocytes, mucous cell metaplasia, and epithelial injury. Currently, the mechanisms that control these events are unclear, and the relative contribution of T-cell subsets to pulmonary pathologies following repeated exposures to irritants is unknown. To examine whether lymphocyte subpopulations regulate inflammation and epithelial cell pathology, we utilized a mouse model of pulmonary pathology induced by repeated acrolein exposures. The role of lymphocyte subsets was examined by utilizing transgenic mice genetically deficient in either alphabeta T cells or gammadelta T cells, and changes in cellular, molecular, and pathologic outcomes associated with repeated inhalation exposure to 2.0 and 0.5 ppm acrolein were measured. To examine the potential functions of lymphocyte subsets, we purified these cells from the lungs of mice repeatedly exposed to 2.0 ppm acrolein, isolated and amplified messenger RNA, and performed microarray analysis. Our data demonstrate that alphabeta T cells are required for macrophage accumulation, whereas gammadelta T cells are critical regulators of epithelial cell homeostasis, as identified by epithelial cell injury and apoptosis, following repeated acrolein exposure. This is supported by microarray analyses that indicated the T-cell subsets are unique in their gene expression profiles following acrolein exposures. Microarray analyses identified several genes that may contribute to phenotypes mediated by T-cell subpopulations including those involved in cytokine receptor signaling, chemotaxis, growth factor production, lymphocyte activation, and apoptosis. These data provide strong evidence that T-cell subpopulations in the lung are major determinants of pulmonary pathology and highlight the advantages of dissecting their effector functions in response to toxicant exposures.

Molecular mechanisms of acrolein toxicity: relevance to human disease.

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Moghe, Akshata; Ghare, Smita; Lamoreau, Bryan; Mohammad, Mohammad; Barve, Shirish; McClain, Craig; Joshi-Barve, Swati

2015-02-01

Acrolein, a highly reactive unsaturated aldehyde, is a ubiquitous environmental pollutant and its potential as a serious environmental health threat is beginning to be recognized. Humans are exposed to acrolein per oral (food and water), respiratory (cigarette smoke, automobile exhaust, and biocide use) and dermal routes, in addition to endogenous generation (metabolism and lipid peroxidation). Acrolein has been suggested to play a role in several disease states including spinal cord injury, multiple sclerosis, Alzheimer's disease, cardiovascular disease, diabetes mellitus, and neuro-, hepato-, and nephro-toxicity. On the cellular level, acrolein exposure has diverse toxic effects, including DNA and protein adduction, oxidative stress, mitochondrial disruption, membrane damage, endoplasmic reticulum stress, and immune dysfunction. This review addresses our current understanding of each pathogenic mechanism of acrolein toxicity, with emphasis on the known and anticipated contribution to clinical disease, and potential therapies. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Proteomic profiling of acrolein adducts in human lung epithelial cells

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Spiess, Page C.; Deng, Bin; Hondal, Robert J.; Matthews, Dwight E.; van der Vliet, Albert

2011-01-01

Acrolein (2,3-propenal) is a major indoor and outdoor air pollutant originating largely from tobacco smoke or organic combustion. Given its high reactivity, the adverse effects of inhaled acrolein are likely due to direct interactions with the airway epithelium, resulting in altered epithelial function, but only limited information exists to date regarding the primary direct cellular targets for acrolein. Here, we describe a global proteomics approach to characterize the spectrum of airway epithelial protein targets for Michael adduction in acrolein-exposed bronchial epithelial (HBE1) cells, based on biotin hydrazide labeling and avidin purification of biotinylated proteins or peptides for analysis by LC-MS/MS. Identified protein targets included a number of stress proteins, cytoskeletal proteins, and several key proteins involved in redox signaling, including thioredoxin reductase, thioredoxin, peroxiredoxins, and glutathione S-transferase π. Because of the central role of thioredoxin reductase in cellular redox regulation, additional LC-MS/MS characterization was performed on purified mitochondrial thioredoxin reductase to identify the specific site of acrolein adduction, revealing the catalytic selenocysteine residue as the target responsible for enzyme inactivation. Our findings indicate that these approaches are useful in characterizing major protein targets for acrolein, and will enhance mechanistic understanding of the impact of acrolein on cell biology. PMID:21704744

On detecting reference level of acrolein content in children's blood

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T.S. Ulanova

2017-03-01

Full Text Available The article gives the results of complex chemical-analytical and clinical-laboratory research in course of which biological media of children living in Perm region were examined. To study impacts exerted by exogenous acrolein we examined 156 children in 2014–2016, aged 5–10, attending pre-school facilities and schools, and living in Perm region. As we conducted this research we detected average annual acrolein concentration in atmosphere on the examined territory; this concentration was equal to 0.000024 mg/m3, and it was 1.2 times higher than reference acrolein concentration in the air for chronic inhalation exposure. Average group acrolein concentration in children's blood was 1.2 times authentically higher (р3.96, p≤0.05. We used increased content of delta-aminolevulinic acid in urine as a limiting marker for effects occurring at chronic inhalation exposure to acrolein. Basing on the results of the performed examination we recommend concentration equal to 0.10 mgr/dm 3 as a reference level of acrolein content in blood at chronic inhalation exposure.

Threshold photoelectron spectroscopy of acetaldehyde and acrolein

International Nuclear Information System (INIS)

Yencha, Andrew J.; Siggel-King, Michele R.F.; King, George C.; Malins, Andrew E.R.; Eypper, Marie

2013-01-01

Highlights: •High-resolution threshold photoelectron spectrum of acetaldehyde. •High-resolution threshold photoelectron spectrum of acrolein. •High-resolution total photoion yield spectrum of acetaldehyde. •High-resolution total photoion yield spectrum of acrolein. •Determination of vertical ionization potentials in acetaldehyde and acrolein. -- Abstract: High-resolution (6 meV and 12 meV) threshold photoelectron (TPE) spectra of acetaldehyde and acrolein (2-propenal) have been recorded over the valence binding energy region 10–20 eV, employing synchrotron radiation and a penetrating-field electron spectrometer. These TPE spectra are presented here for the first time. All of the band structures observed in the TPE spectra replicate those found in their conventional HeI photoelectron (PE) spectra. However, the relative band intensities are found to be dramatically different in the two types of spectra that are attributed to the different dominant operative formation mechanisms. In addition, some band shapes and their vertical ionization potentials are found to differ in the two types of spectra that are associated with the autoionization of Rydberg states in the two molecules

SCGB3A2 Inhibits Acrolein-Induced Apoptosis through Decreased p53 Phosphorylation.

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Kurotani, Reiko; Shima, Reika; Miyano, Yuki; Sakahara, Satoshi; Matsumoto, Yoshie; Shibata, Yoko; Abe, Hiroyuki; Kimura, Shioko

2015-04-28

Chronic obstructive pulmonary disease (COPD), a major global health problem with increasing morbidity and mortality rates, is anticipated to become the third leading cause of death worldwide by 2020. COPD arises from exposure to cigarette smoke. Acrolein, which is contained in cigarette smoke, is the most important risk factor for COPD. It causes lung injury through altering apoptosis and causes inflammation by augmenting p53 phosphorylation and producing reactive oxygen species (ROS). Secretoglobin (SCGB) 3A2, a secretory protein predominantly present in the epithelial cells of the lungs and trachea, is a cytokine-like small molecule having anti-inflammatory, antifibrotic, and growth factor activities. In this study, the effect of SCGB3A2 on acrolein-related apoptosis was investigated using the mouse fibroblast cell line MLg as the first step in determining the possible therapeutic value of SCGB3A2 in COPD. Acrolein increased the production of ROS and phosphorylation of p53 and induced apoptosis in MLg cells. While the extent of ROS production induced by acrolein was not affected by SCGB3A2, p53 phosphorylation was significantly decreased by SCGB3A2. These results demonstrate that SCGB3A2 inhibited acrolein-induced apoptosis through decreased p53 phosphorylation, not altered ROS levels.

SCGB3A2 Inhibits Acrolein-Induced Apoptosis through Decreased p53 Phosphorylation

International Nuclear Information System (INIS)

Kurotani, Reiko; Shima, Reika; Miyano, Yuki; Sakahara, Satoshi; Matsumoto, Yoshie; Shibata, Yoko; Abe, Hiroyuki; Kimura, Shioko

2015-01-01

Chronic obstructive pulmonary disease (COPD), a major global health problem with increasing morbidity and mortality rates, is anticipated to become the third leading cause of death worldwide by 2020. COPD arises from exposure to cigarette smoke. Acrolein, which is contained in cigarette smoke, is the most important risk factor for COPD. It causes lung injury through altering apoptosis and causes inflammation by augmenting p53 phosphorylation and producing reactive oxygen species (ROS). Secretoglobin (SCGB) 3A2, a secretory protein predominantly present in the epithelial cells of the lungs and trachea, is a cytokine-like small molecule having anti-inflammatory, antifibrotic, and growth factor activities. In this study, the effect of SCGB3A2 on acrolein-related apoptosis was investigated using the mouse fibroblast cell line MLg as the first step in determining the possible therapeutic value of SCGB3A2 in COPD. Acrolein increased the production of ROS and phosphorylation of p53 and induced apoptosis in MLg cells. While the extent of ROS production induced by acrolein was not affected by SCGB3A2, p53 phosphorylation was significantly decreased by SCGB3A2. These results demonstrate that SCGB3A2 inhibited acrolein-induced apoptosis through decreased p53 phosphorylation, not altered ROS levels

TRPA1 mediates changes in heart rate variability and cardiac mechanical function in mice exposed to acrolein

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Kurhanewicz, Nicole [Curriculum in Toxicology, School of Medicine, University of North Carolina, Chapel Hill, NC 27599 (United States); McIntosh-Kastrinsky, Rachel [Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599 (United States); Tong, Haiyan; Ledbetter, Allen; Walsh, Leon; Farraj, Aimen [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Hazari, Mehdi, E-mail: hazari.mehdi@epa.gov [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, NC 27711 (United States)

2017-06-01

Short-term exposure to ambient air pollution is linked with adverse cardiovascular effects. While previous research focused primarily on particulate matter-induced responses, gaseous air pollutants also contribute to cause short-term cardiovascular effects. Mechanisms underlying such effects have not been adequately described, however the immediate nature of the response suggests involvement of irritant neural activation and downstream autonomic dysfunction. Thus, this study examines the role of TRPA1, an irritant sensory receptor found in the airways, in the cardiac response of mice to acrolein and ozone. Conscious unrestrained wild-type C57BL/6 (WT) and TRPA1 knockout (KO) mice implanted with radiotelemeters were exposed once to 3 ppm acrolein, 0.3 ppm ozone, or filtered air. Heart rate (HR) and electrocardiogram (ECG) were recorded continuously before, during and after exposure. Analysis of ECG morphology, incidence of arrhythmia and heart rate variability (HRV) were performed. Cardiac mechanical function was assessed using a Langendorff perfusion preparation 24 h post-exposure. Acrolein exposure increased HRV independent of HR, as well as incidence of arrhythmia. Acrolein also increased left ventricular developed pressure in WT mice at 24 h post-exposure. Ozone did not produce any changes in cardiac function. Neither gas produced ECG effects, changes in HRV, arrhythmogenesis, or mechanical function in KO mice. These data demonstrate that a single exposure to acrolein causes cardiac dysfunction through TRPA1 activation and autonomic imbalance characterized by a shift toward parasympathetic modulation. Furthermore, it is clear from the lack of ozone effects that although gaseous irritants are capable of eliciting immediate cardiac changes, gas concentration and properties play important roles. - Highlights: • Acute acrolein exposure causes autonomic imbalance and altered CV function in mice. • TRPA1 mediates acrolein-induced autonomic nervous system cardiac

TRPA1 mediates changes in heart rate variability and cardiac mechanical function in mice exposed to acrolein

International Nuclear Information System (INIS)

Kurhanewicz, Nicole; McIntosh-Kastrinsky, Rachel; Tong, Haiyan; Ledbetter, Allen; Walsh, Leon; Farraj, Aimen; Hazari, Mehdi

2017-01-01

Short-term exposure to ambient air pollution is linked with adverse cardiovascular effects. While previous research focused primarily on particulate matter-induced responses, gaseous air pollutants also contribute to cause short-term cardiovascular effects. Mechanisms underlying such effects have not been adequately described, however the immediate nature of the response suggests involvement of irritant neural activation and downstream autonomic dysfunction. Thus, this study examines the role of TRPA1, an irritant sensory receptor found in the airways, in the cardiac response of mice to acrolein and ozone. Conscious unrestrained wild-type C57BL/6 (WT) and TRPA1 knockout (KO) mice implanted with radiotelemeters were exposed once to 3 ppm acrolein, 0.3 ppm ozone, or filtered air. Heart rate (HR) and electrocardiogram (ECG) were recorded continuously before, during and after exposure. Analysis of ECG morphology, incidence of arrhythmia and heart rate variability (HRV) were performed. Cardiac mechanical function was assessed using a Langendorff perfusion preparation 24 h post-exposure. Acrolein exposure increased HRV independent of HR, as well as incidence of arrhythmia. Acrolein also increased left ventricular developed pressure in WT mice at 24 h post-exposure. Ozone did not produce any changes in cardiac function. Neither gas produced ECG effects, changes in HRV, arrhythmogenesis, or mechanical function in KO mice. These data demonstrate that a single exposure to acrolein causes cardiac dysfunction through TRPA1 activation and autonomic imbalance characterized by a shift toward parasympathetic modulation. Furthermore, it is clear from the lack of ozone effects that although gaseous irritants are capable of eliciting immediate cardiac changes, gas concentration and properties play important roles. - Highlights: • Acute acrolein exposure causes autonomic imbalance and altered CV function in mice. • TRPA1 mediates acrolein-induced autonomic nervous system cardiac

Simvastatin attenuates acrolein-induced mucin production in rats: involvement of the Ras/extracellular signal-regulated kinase pathway.

Science.gov (United States)

Chen, Ya-Juan; Chen, Peng; Wang, Hai-Xia; Wang, Tao; Chen, Lei; Wang, Xun; Sun, Bei-Bei; Liu, Dai-Shun; Xu, Dan; An, Jing; Wen, Fu-Qiang

2010-06-01

Airway mucus overproduction is a cardinal feature of airway inflammatory diseases, such as chronic obstructive pulmonary disease and cystic fibrosis. Since the small G-protein Ras is known to modulate cellular functions in the lung, we sought to investigate whether the Ras inhibitor simvastatin could attenuate acrolein-induced mucin production in rat airways. Rats were exposed to acrolein for 12 days, after first being pretreated intragastrically for 24 h with either simvastatin alone or simvastatin in combination with mevalonate, which prevents the isoprenylation needed for Ras activation. Lung tissue was analyzed for extracellular signal-regulated kinase (ERK) activity, goblet cell metaplasia and mucin production. To analyze the effect of simvastatin on mucin production in more detail, acrolein-exposed human airway epithelial NCI-H292 cells were pretreated with simvastatin alone or together with mevalonate. Culture medium was collected to detect mucin secretion, and cell lysates were examined for Ras-GTPase activity and epidermal growth factor receptor (EGFR)/ERK phosphorylation. In vivo, simvastatin treatment dose-dependently suppressed acrolein-induced goblet cell hyperplasia and metaplasia in bronchial epithelium and inhibited ERK phosphorylation in rat lung homogenates. Moreover, simvastatin inhibited Muc5AC mucin synthesis at both the mRNA and protein levels in the lung. In vitro, simvastatin pretreatment attenuated the acrolein-induced significant increase in MUC5AC mucin expression, Ras-GTPase activity and EGFR/ERK phosphorylation. These inhibitory effects of simvastatin were neutralized by mevalonate administration both in vitro and in vivo. Our results suggest that simvastatin may attenuate acrolein-induced mucin protein synthesis in the airway and airway inflammation, possibly by blocking ERK activation mediated by Ras protein isoprenylation. Thus, the evidence from the experiment suggests that human trials are warranted to determine the potential

Iron-tellurium-selenium mixed oxide catalysts for the selective oxidation of propylene to acrolein

International Nuclear Information System (INIS)

Patel, B.M.; Price, G.L.

1990-01-01

This paper reports on iron-tellurium-selenium mixed oxide catalysts prepared by coprecipitation from aqueous solution investigated for the propylene to acrolein reaction in the temperature range 543-773 K. Infrared spectroscopy, electron dispersive X-ray analysis, X-ray diffraction, and isotopic tracer techniques have also been employed to characterize this catalytic system. Properties of the Fe-Te-Se mixed oxide catalysts have been compared with Fe-Te mixed oxides in an effort to deduce the functionality of Se. The selenium in the Fe-Te-Se-O catalyst has been found to be the hydrocarbon activating site. The activation energies for the acrolein and carbon dioxide formation are 71 and 54 kJ/mol, respectively. Reactions carried out with 18 O 2 have shown lattice oxygen to be primarily responsible for the formation of both acrolein and carbon dioxide. The initial and rate-determining step for acrolein formation is hydrogen abstraction as determined by an isotope effect associated with the C 3 D 6 reaction. No isotope effect is observed for carbon dioxide formation from C 3 D 6 suggesting that CO 2 is formed by parallel, not consecutive, oxidation of propylene

Acrolein induction of oxidative stress and degranulation in mast cells.

Science.gov (United States)

Hochman, Daniel J; Collaco, Christopher R; Brooks, Edward G

2014-08-01

Increases in asthma worldwide have been associated epidemiologically with expanding urban air pollution. The mechanistic relationship between airway hyper-responsiveness, inflammation, and ambient airborne triggers remains ambiguous. Acrolein, a ubiquitous aldehyde pollutant, is a product of incomplete combustion reactions. Acrolein is abundant in cigarette smoke, effluent from industrial smokestacks, diesel exhaust, and even hot oil cooking vapors. Acrolein is a potent airway irritant and can induce airway hyper-responsiveness and inflammation in the lungs of animal models. In the present study, we utilized the mast cell analog, RBL-2H3, to interrogate the responses of cells relevant to airway inflammation and allergic responses as a model for the induction of asthma-like conditions upon exposure to acrolein. We hypothesized that acrolein would induce oxidative stress and degranulation in airway mast cells. Our results indicate that acrolein at 1 ppm initiated degranulation and promoted the generation of reactive oxygen species (ROS). Introduction of antioxidants to the system significantly reduced both ROS generation and degranulation. At higher levels of exposure (above 100 ppm), RBL-2H3 cells displayed signs of severe toxicity. This experimental data indicates acrolein can induce an allergic inflammation in mast cell lines, and the initiation of degranulation was moderated by the application of antioxidants. Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.

Indoor acrolein emission and decay rates resulting from domestic cooking events

Science.gov (United States)

Seaman, Vincent Y.; Bennett, Deborah H.; Cahill, Thomas M.

2009-12-01

Acrolein (2-propenal) is a common constituent of both indoor and outdoor air, can exacerbate asthma in children, and may contribute to other chronic lung diseases. Recent studies have found high indoor levels of acrolein and other carbonyls compared to outdoor ambient concentrations. Heated cooking oils produce considerable amounts of acrolein, thus cooking is likely an important source of indoor acrolein. A series of cooking experiments were conducted to determine the emission rates of acrolein and other volatile carbonyls for different types of cooking oils (canola, soybean, corn and olive oils) and deep-frying different food items. Similar concentrations and emission rates of carbonyls were found when different vegetable oils were used to deep-fry the same food product. The food item being deep-fried was generally not a significant source of carbonyls compared to the cooking oil. The oil cooking events resulted in high concentrations of acrolein that were in the range of 26.4-64.5 μg m -3. These concentrations exceed all the chronic regulatory exposure limits and many of the acute exposure limits. The air exchange rate and the decay rate of the carbonyls were monitored to estimate the half-life of the carbonyls. The half-life for acrolein was 14.4 ± 2.6 h, which indicates that indoor acrolein concentrations can persist for considerable time after cooking in poorly-ventilated homes.

Scavenging of Toxic Acrolein by Resveratrol and Hesperetin and Identification of Adducts.

Science.gov (United States)

Wang, Weixin; Qi, Yajing; Rocca, James R; Sarnoski, Paul J; Jia, Aiqun; Gu, Liwei

2015-11-04

The objective of this study was to investigate the ability of resveratrol and hesperetin to scavenge acrolein at pH 7.4 and 37 °C. About 6.4 or 5.2% of acrolein remained after reaction with resveratrol or hesperetin for 12 h at equimolar concentrations. An acrolein-resveratrol adduct and two acrolein-hesperetin adducts were isolated. Their structures were elucidated using mass and NMR spectroscopy. Acrolein reacted with resveratrol at the C-2 and C-3 positions through nucleophilic addition and formed an additional heterocyclic ring. Two similar monoacrolein-conjugated adducts were identified for hesperetin. Spectroscopic data suggested each acrolein-hesperetin adduct was a mixture of four stereoisomers due to the existence of two chiral carbon atoms. Yield of adducts was low at pH 5.4 but increased at pH 7.4 and 8.4. Higher pH also promoted the formation of diacrolein adducts. Results suggest that resveratrol and hesperetin exert health benefits in part through neutralizing toxic acrolein in vivo.

Hydralazine inhibits compression and acrolein-mediated injuries in ex vivo spinal cord.

Science.gov (United States)

Hamann, Kristin; Nehrt, Genevieve; Ouyang, Hui; Duerstock, Brad; Shi, Riyi

2008-02-01

We have previously shown that acrolein, a lipid peroxidation byproduct, is significantly increased following spinal cord injury in vivo, and that exposure to neuronal cells results in oxidative stress, mitochondrial dysfunction, increased membrane permeability, impaired axonal conductivity, and eventually cell death. Acrolein thus may be a key player in the pathogenesis of spinal cord injury, where lipid peroxidation is known to be involved. The current study demonstrates that the acrolein scavenger hydralazine protects against not only acrolein-mediated injury, but also compression in guinea pig spinal cord ex vivo. Specifically, hydralazine (500 mumol/L to 1 mmol/L) can significantly alleviate acrolein (100-500 mumol/L)-induced superoxide production, glutathione depletion, mitochondrial dysfunction, loss of membrane integrity, and reduced compound action potential conduction. Additionally, 500 mumol/L hydralazine significantly attenuated compression-mediated membrane disruptions at 2 and 3 h following injury. This was consistent with our findings that acrolein-lys adducts were increased following compression injury ex vivo, an effect that was prevented by hydralazine treatment. These findings provide further evidence for the role of acrolein in spinal cord injury, and suggest that acrolein-scavenging drugs such as hydralazine may represent a novel therapy to effectively reduce oxidative stress in disorders such as spinal cord injury and neurodegenerative diseases, where oxidative stress is known to play a role.

Pyrolysis of D-Glucose to Acrolein

Science.gov (United States)

Shen, Chong; Zhang, Igor Ying; Fu, Gang; Xu, Xin

2011-06-01

Despite of its great importance, the detailed molecular mechanism for carbohydrate pyrolysis remains poorly understood. We perform a density functional study with a newly developed XYG3 functional on the processes for D-glucose pyrolysis to acrolein. The most feasible reaction pathway starts from an isomerization from D-glucose to D-fructose, which then undergoes a cyclic Grob fragmentation, followed by a concerted electrocyclic dehydration to yield acrolein. This mechanism can account for the known experimental results.

Acrolein detection: potential theranostic utility in multiple sclerosis and spinal cord injury.

Science.gov (United States)

Tully, Melissa; Zheng, Lingxing; Shi, Riyi

2014-06-01

Oxidative stress has been implicated as a major pathological process underlying CNS disease and trauma. More specifically, acrolein, an unsaturated aldehyde, produced by way of lipid peroxidation, has been shown to play a crucial role in initiating and perpetuating detrimental effects associated with multiple sclerosis and spinal cord injury. In light of these findings, quantification of acrolein levels both systemically and locally could allow for the use of acrolein as a biomarker to aid in diagnosis and guide treatment regimens. The three main approaches currently available are acrolein derivatization followed by LC/GC-MS, application of an acrolein antibody and subsequent immunoblotting, and the 3-hydroxypropylmercapturic acid-based method. Of these three strategies, the 3-hydroxypropylmercapturic acid-based method is the least invasive allowing for rapid translation of acrolein detection into a clinical setting.

Activation of the microsomal glutathione-S-transferase and reduction of the glutathione dependent protection against lipid peroxidation by acrolein

NARCIS (Netherlands)

Haenen, G R; Vermeulen, N P; Tai Tin Tsoi, J N; Ragetli, H M; Timmerman, H; Blast, A

1988-01-01

Allyl alcohol is hepatotoxic. It is generally believed that acrolein, generated out of allyl alcohol by cytosolic alcohol dehydrogenase, is responsible for this toxicity. The effect of acrolein in vitro and in vivo on the glutathione (GSH) dependent protection of liver microsomes against lipid

Spermine oxidase promotes bile canalicular lumen formation through acrolein production.

Science.gov (United States)

Uemura, Takeshi; Takasaka, Tomokazu; Igarashi, Kazuei; Ikegaya, Hiroshi

2017-11-01

Spermine oxidase (SMOX) catalyzes oxidation of spermine to generate spermidine, hydrogen peroxide (H 2 O 2 ) and 3-aminopropanal, which is spontaneously converted to acrolein. SMOX is induced by a variety of stimuli including bacterial infection, polyamine analogues and acetaldehyde exposure. However, the physiological functions of SMOX are not yet fully understood. We investigated the physiological role of SMOX in liver cells using human hepatocellular carcinoma cell line HepG2. SMOX localized to the bile canalicular lumen, as determined by F-actin staining. Knockdown of SMOX reduced the formation of bile canalicular lumen. We also found that phospho-Akt (phosphorylated protein kinase B) was localized to canalicular lumen. Treatment with Akt inhibitor significantly reduced the formation of bile canalicular lumen. Acrolein scavenger also inhibited the formation of bile canalicular lumen. PTEN, phosphatase and tensin homolog and an inhibitor of Akt, was alkylated in a SMOX-dependent manner. Our results suggest that SMOX plays a central role in the formation of bile canalicular lumen in liver cells by activating Akt pathway through acrolein production.

Conjugation vs hyperconjugation in molecular structure of acrolein

Science.gov (United States)

Shishkina, Svitlana V.; Slabko, Anzhelika I.; Shishkin, Oleg V.

2013-01-01

Analysis of geometric parameters of butadiene and acrolein reveals the contradiction between the Csp2-Csp2 bond length in acrolein and classical concept of conjugation degree in the polarized molecules. In this Letter the reasons of this contradiction have been investigated. It is concluded that the Csp2-Csp2 bond length in acrolein is determined by influence of the bonding for it π-π conjugation and antibonding n → σ∗ hyperconjugation between the oxygen lone pair and the antibonding orbital of the single bond. It was shown also this bond length depends on the difference in energy of conjugative and hyperconjugative interactions.

Acrolein Modification Impairs Key Functional Features of Rat Apolipoprotein E: Identification of Modified Sites by Mass Spectrometry

Science.gov (United States)

Tran, Tuyen N.; Kosaraju, Malathi G.; Tamamizu-Kato, Shiori; Akintunde, Olayemi; Zheng, Ying; Bielicki, John K.; Pinkerton, Kent; Uchida, Koji; Lee, Yuan Yu; Narayanaswami, Vasanthy

2014-01-01

Apolipoprotein E (apoE), an anti-atherogenic apolipoprotein, plays a significant role in the metabolism of lipoproteins. It lowers plasma lipid levels by acting as a ligand for low-density lipoprotein receptor (LDLr) family of proteins, in addition to playing a role in promoting macrophage cholesterol efflux in atherosclerotic lesions. The objective of this study is to examine the effect of acrolein modification on the structure and function of rat apoE and to determine sites and nature of modification by mass spectrometry. Acrolein is a highly reactive aldehyde, which is generated endogenously as one of the products of lipid peroxidation and is present in the environment in pollutants such as tobacco smoke and heated oils. In initial studies, acrolein-modified apoE was identified by immunoprecipitation using an acrolein-lysine specific antibody, in the plasma of ten-week old male rats that were exposed to filtered air (FA) or low doses of environmental tobacco smoke (ETS). While both groups displayed acrolein-modified apoE in the lipoprotein fraction, the ETS group had higher levels in lipid-free fraction compared to the FA group. This observation provided the rationale to further investigate the effect of acrolein modification on rat apoE at a molecular level. Treatment of recombinant rat apoE with a 10-fold molar excess of acrolein resulted in: (i) a significant decrease in lipid-binding and cholesterol efflux abilities, (ii) impairment in the LDLr- and heparin-binding capabilities, and (iii) significant alterations in the overall stability of the protein. The disruption in the functional abilities is attributed directly or indirectly to acrolein modification yielding: an aldimine adduct at K149 and K155 (+38); a propanal adduct at K135 and K138 (+56); an Nε-(3-methylpyridinium)lysine (MP-lysine) at K64, K67 and K254 (+76), and Nε-(3-formyl-3,4-dehydropiperidino)lysine (FDP-lysine) derivative at position K68 (+94), as determined by Matrix-Assisted Laser

Chitosan nanoparticle-based neuronal membrane sealing and neuroprotection following acrolein-induced cell injury

Directory of Open Access Journals (Sweden)

Shi Riyi

2010-01-01

Full Text Available Abstract Background The highly reactive aldehyde acrolein is a very potent endogenous toxin with a long half-life. Acrolein is produced within cells after insult, and is a central player in slow and progressive "secondary injury" cascades. Indeed, acrolein-biomolecule complexes formed by cross-linking with proteins and DNA are associated with a number of pathologies, especially central nervous system (CNS trauma and neurodegenerative diseases. Hydralazine is capable of inhibiting or reducing acrolein-induced damage. However, since hydralazine's principle activity is to reduce blood pressure as a common anti-hypertension drug, the possible problems encountered when applied to hypotensive trauma victims have led us to explore alternative approaches. This study aims to evaluate such an alternative - a chitosan nanoparticle-based therapeutic system. Results Hydralazine-loaded chitosan nanoparticles were prepared using different types of polyanions and characterized for particle size, morphology, zeta potential value, and the efficiency of hydralazine entrapment and release. Hydralazine-loaded chitosan nanoparticles ranged in size from 300 nm to 350 nm in diameter, and with a tunable, or adjustable, surface charge. Conclusions We evaluated the utility of chitosan nanoparticles with an in-vitro model of acrolein-mediated cell injury using PC -12 cells. The particles effectively, and statistically, reduced damage to membrane integrity, secondary oxidative stress, and lipid peroxidation. This study suggests that a chitosan nanoparticle-based therapy to interfere with "secondary" injury may be possible.

Acrolein cytotoxicity in hepatocytes involves endoplasmic reticulum stress, mitochondrial dysfunction and oxidative stress

OpenAIRE

Mohammad, Mohammad K; Avila, Diana; Zhang, Jingwen; Barve, Shirish; Arteel, Gavin; McClain, Craig; Joshi-Barve, Swati

2012-01-01

Acrolein is a common environmental, food and water pollutant and a major component of cigarette smoke. Also, it is produced endogenously via lipid peroxidation and cellular metabolism of certain amino acids and drugs. Acrolein is cytotoxic to many cell types including hepatocytes; however the mechanisms are not fully understood. We examined the molecular mechanisms underlying acrolein hepatotoxicity in primary human hepatocytes and hepatoma cells. Acrolein, at pathophysiological concentration...

POTENTIATION OF PULMONARY REFLEX RESPONSE TO CAPSAICIN 24 HOURS FOLLOWING WHOLE-BODY ACROLEIN EXPOSURE IS MEDIATED BY TRPV1

Science.gov (United States)

Pulmonary C-fibers are stimulated by irritant air pollutants producing apnea, bronchospasm, and decrease in HR. C-fiber chemoreflex activation is mediated by TRPV1 and release of substance P. While acrolein has been shown to stimulate C-fibers, the persistence of acrolein effect...

Idh2 Deficiency Exacerbates Acrolein-Induced Lung Injury through Mitochondrial Redox Environment Deterioration

Directory of Open Access Journals (Sweden)

Jung Hyun Park

2017-01-01

Full Text Available Acrolein is known to be involved in acute lung injury and other pulmonary diseases. A number of studies have suggested that acrolein-induced toxic effects are associated with depletion of antioxidants, such as reduced glutathione and protein thiols, and production of reactive oxygen species. Mitochondrial NADP+-dependent isocitrate dehydrogenase (idh2 regulates mitochondrial redox balance and reduces oxidative stress-induced cell injury via generation of NADPH. Therefore, we evaluated the role of idh2 in acrolein-induced lung injury using idh2 short hairpin RNA- (shRNA- transfected Lewis lung carcinoma (LLC cells and idh2-deficient (idh2−/− mice. Downregulation of idh2 expression increased susceptibility to acrolein via induction of apoptotic cell death due to elevated mitochondrial oxidative stress. Idh2 deficiency also promoted acrolein-induced lung injury in idh2 knockout mice through the disruption of mitochondrial redox status. In addition, acrolein-induced toxicity in idh2 shRNA-transfected LLC cells and in idh2 knockout mice was ameliorated by the antioxidant, N-acetylcysteine, through attenuation of oxidative stress resulting from idh2 deficiency. In conclusion, idh2 deficiency leads to mitochondrial redox environment deterioration, which causes acrolein-mediated apoptosis of LLC cells and acrolein-induced lung injury in idh2−/− mice. The present study supports the central role of idh2 deficiency in inducing oxidative stress resulting from acrolein-induced disruption of mitochondrial redox status in the lung.

Idh2 Deficiency Exacerbates Acrolein-Induced Lung Injury through Mitochondrial Redox Environment Deterioration.

Science.gov (United States)

Park, Jung Hyun; Ku, Hyeong Jun; Lee, Jin Hyup; Park, Jeen-Woo

2017-01-01

Acrolein is known to be involved in acute lung injury and other pulmonary diseases. A number of studies have suggested that acrolein-induced toxic effects are associated with depletion of antioxidants, such as reduced glutathione and protein thiols, and production of reactive oxygen species. Mitochondrial NADP + -dependent isocitrate dehydrogenase ( idh2 ) regulates mitochondrial redox balance and reduces oxidative stress-induced cell injury via generation of NADPH. Therefore, we evaluated the role of idh2 in acrolein-induced lung injury using idh2 short hairpin RNA- (shRNA-) transfected Lewis lung carcinoma (LLC) cells and idh2 -deficient ( idh2 -/- ) mice. Downregulation of idh2 expression increased susceptibility to acrolein via induction of apoptotic cell death due to elevated mitochondrial oxidative stress. Idh2 deficiency also promoted acrolein-induced lung injury in idh2 knockout mice through the disruption of mitochondrial redox status. In addition, acrolein-induced toxicity in idh2 shRNA-transfected LLC cells and in idh2 knockout mice was ameliorated by the antioxidant, N-acetylcysteine, through attenuation of oxidative stress resulting from idh2 deficiency. In conclusion, idh2 deficiency leads to mitochondrial redox environment deterioration, which causes acrolein-mediated apoptosis of LLC cells and acrolein-induced lung injury in idh2 -/- mice. The present study supports the central role of idh2 deficiency in inducing oxidative stress resulting from acrolein-induced disruption of mitochondrial redox status in the lung.

Vapour phase dehydration of glycerol to acrolein over tungstated zirconia catalysts

Science.gov (United States)

Rao Ginjupalli, Srinivasa; Mugawar, Sowmya; Rajan N., Pethan; Kumar Balla, Putra; Chary Komandur, V. R.

2014-08-01

Tetragonal (TZ) and monoclinic (MZ) polymorphs of zirconia supports were synthesised by sol-gel method followed by variation of the calcination temperature. Tungstated (10 wt% WO3) supported on the zirconia polymorphs were prepared by impregnation method by using ammonium metatungstate precursor. The physico-chemical properties of the calcined catalysts were characterised by X-ray diffraction, UV-vis diffused reflectance spectroscopy, X-ray photoelectron spectroscopy (XPS), surface area and pore size distribution measurements to gain insight into the effect of morphology of the catalyst textural properties, and structure. The surface acidic properties have been determined by NH3 TPD method and also with FT-IR spectra of pyridine adsorption. Vapour phase dehydration of glycerol to acrolein was employed to investigate the catalytic functionalities. Glycerol conversion and acrolein selectivity was mainly dependent on the fraction of moderate acid sites with majority of them are due to Brønsted acidic sites. Monoclinic zirconia based catalysts have shown the highest activity and acrolein selectivity compared to the corresponding tetragonal zirconia catalysts.

Vapour phase dehydration of glycerol to acrolein over tungstated zirconia catalysts

International Nuclear Information System (INIS)

Rao Ginjupalli, Srinivasa; Mugawar, Sowmya; Rajan, Pethan N.; Kumar Balla, Putra; Chary Komandur, V.R.

2014-01-01

Tetragonal (TZ) and monoclinic (MZ) polymorphs of zirconia supports were synthesised by sol–gel method followed by variation of the calcination temperature. Tungstated (10 wt% WO 3 ) supported on the zirconia polymorphs were prepared by impregnation method by using ammonium metatungstate precursor. The physico-chemical properties of the calcined catalysts were characterised by X-ray diffraction, UV–vis diffused reflectance spectroscopy, X-ray photoelectron spectroscopy (XPS), surface area and pore size distribution measurements to gain insight into the effect of morphology of the catalyst textural properties, and structure. The surface acidic properties have been determined by NH 3 TPD method and also with FT-IR spectra of pyridine adsorption. Vapour phase dehydration of glycerol to acrolein was employed to investigate the catalytic functionalities. Glycerol conversion and acrolein selectivity was mainly dependent on the fraction of moderate acid sites with majority of them are due to Brønsted acidic sites. Monoclinic zirconia based catalysts have shown the highest activity and acrolein selectivity compared to the corresponding tetragonal zirconia catalysts.

Vapour phase dehydration of glycerol to acrolein over tungstated zirconia catalysts

Energy Technology Data Exchange (ETDEWEB)

Rao Ginjupalli, Srinivasa; Mugawar, Sowmya; Rajan, Pethan N.; Kumar Balla, Putra; Chary Komandur, V.R., E-mail: kvrchary@iict.res.in

2014-08-01

Tetragonal (TZ) and monoclinic (MZ) polymorphs of zirconia supports were synthesised by sol–gel method followed by variation of the calcination temperature. Tungstated (10 wt% WO{sub 3}) supported on the zirconia polymorphs were prepared by impregnation method by using ammonium metatungstate precursor. The physico-chemical properties of the calcined catalysts were characterised by X-ray diffraction, UV–vis diffused reflectance spectroscopy, X-ray photoelectron spectroscopy (XPS), surface area and pore size distribution measurements to gain insight into the effect of morphology of the catalyst textural properties, and structure. The surface acidic properties have been determined by NH{sub 3} TPD method and also with FT-IR spectra of pyridine adsorption. Vapour phase dehydration of glycerol to acrolein was employed to investigate the catalytic functionalities. Glycerol conversion and acrolein selectivity was mainly dependent on the fraction of moderate acid sites with majority of them are due to Brønsted acidic sites. Monoclinic zirconia based catalysts have shown the highest activity and acrolein selectivity compared to the corresponding tetragonal zirconia catalysts.

Protective effect of Pycnogenol in human neuroblastoma SH-SY5Y cells following acrolein-induced cytotoxicity.

Science.gov (United States)

Ansari, Mubeen A; Keller, Jeffrey N; Scheff, Stephen W

2008-12-01

Oxidative stress is one of the hypotheses involved in the etiology of Alzheimer's disease (AD). Considerable attention has been focused on increasing the intracellular glutathione (GSH) levels in many neurodegenerative diseases, including AD. Pycnogenol (PYC) has antioxidant properties and stabilizes intracellular antioxidant defense systems including glutathione levels. The present study investigated the protective effects of PYC on acrolein-induced oxidative cell toxicity in cultured SH-SY5Y neuroblastoma cells. Decreased cell survival in SH-SY5Y cultures treated with acrolein correlated with oxidative stress, increased NADPH oxidase activity, free radical production, protein oxidation/nitration (protein carbonyl, 3-nitrotyrosine), and lipid peroxidation (4-hydroxy-2-nonenal). Pretreatment with PYC significantly attenuated acrolein-induced cytotoxicity, protein damage, lipid peroxidation, and cell death. A dose-response study suggested that PYC showed protective effects against acrolein toxicity by modulating oxidative stress and increasing GSH. These findings provide support that PYC may provide a promising approach for the treatment of oxidative stress-related neurodegenerative diseases such as AD.

Acrolein impairs the cholesterol transport functions of high density lipoproteins.

Science.gov (United States)

Chadwick, Alexandra C; Holme, Rebecca L; Chen, Yiliang; Thomas, Michael J; Sorci-Thomas, Mary G; Silverstein, Roy L; Pritchard, Kirkwood A; Sahoo, Daisy

2015-01-01

High density lipoproteins (HDL) are considered athero-protective, primarily due to their role in reverse cholesterol transport, where they transport cholesterol from peripheral tissues to the liver for excretion. The current study was designed to determine the impact of HDL modification by acrolein, a highly reactive aldehyde found in high abundance in cigarette smoke, on the cholesterol transport functions of HDL. HDL was chemically-modified with acrolein and immunoblot and mass spectrometry analyses confirmed apolipoprotein crosslinking, as well as acrolein adducts on apolipoproteins A-I and A-II. The ability of acrolein-modified HDL (acro-HDL) to serve as an acceptor of free cholesterol (FC) from COS-7 cells transiently expressing SR-BI was significantly decreased. Further, in contrast to native HDL, acro-HDL promotes higher neutral lipid accumulation in murine macrophages as judged by Oil Red O staining. The ability of acro-HDL to mediate efficient selective uptake of HDL-cholesteryl esters (CE) into SR-BI-expressing cells was reduced compared to native HDL. Together, the findings from our studies suggest that acrolein modification of HDL produces a dysfunctional particle that may ultimately promote atherogenesis by impairing functions that are critical in the reverse cholesterol transport pathway.

Vocal fold ion transport and mucin expression following acrolein exposure.

Science.gov (United States)

Levendoski, Elizabeth Erickson; Sivasankar, M Preeti

2014-05-01

The vocal fold epithelium is exposed to inhaled particulates including pollutants during breathing in everyday environments. Yet, our understanding of the effects of pollutants on vocal fold epithelial function is extremely limited. The objective of this study was to investigate the effect of the pollutant acrolein on two vocal fold epithelial mechanisms: ion transport and mucin (MUC) synthesis. These mechanisms were chosen as each plays a critical role in vocal defense and in maintaining surface hydration which is necessary for optimal voice production. Healthy, native porcine vocal folds (N = 85) were excised and exposed to an acrolein or sham challenge. A 60-min acrolein, but not sham challenge significantly reduced ion transport and inhibited cyclic adenosine monophosphate-dependent, increases in ion transport. Decreases in ion transport were associated with reduced sodium absorption. Within the same timeline, no significant acrolein-induced changes in MUC gene or protein expression were observed. These results improve our understanding of the effects of acrolein on key vocal fold epithelial functions and inform the development of future investigations that seek to elucidate the impact of a wide range of pollutant exposures on vocal fold health.

Acrolein-induced cell death in PC12 cells: role of mitochondria-mediated oxidative stress.

Science.gov (United States)

Luo, Jian; Robinson, J Paul; Shi, Riyi

2005-12-01

Oxidative stress has been implicated in acrolein cytotoxicity in various cell types, including mammalian spinal cord tissue. In this study we report that acrolein also decreases PC12 cell viability in a reactive oxygen species (ROS)-dependent manner. Specifically, acrolein-induced cell death, mainly necrosis, is accompanied by the accumulation of cellular ROS. Elevating ROS scavengers can alleviate acrolein-induced cell death. Furthermore, we show that exposure to acrolein leads to mitochondrial dysfunction, denoted by the loss of mitochondrial transmembrane potential, reduction of cellular oxygen consumption, and decrease of ATP level. This raises the possibility that the cellular accumulation of ROS could result from the increased production of ROS in the mitochondria of PC12 cells as a result of exposure to acrolein. The acrolein-induced significant decrease of ATP production in mitochondria may also explain why necrosis, not apoptosis, is the dominant type of cell death. In conclusion, our data suggest that one possible mechanism of acrolein-induced cell death could be through mitochondria as its initial target. The subsequent increase of ROS then inflicts cell death and further worsens mitochondria function. Such mechanism may play an important role in CNS trauma and neurodegenerative diseases.

Crude glycerol combustion: Particulate, acrolein, and other volatile organic emissions

KAUST Repository

Steinmetz, Scott; Herrington, Jason S.; Winterrowd, Chris K.; Roberts, William L.; Wendt, Jost O L; Linak, William P.

2013-01-01

to be formed from the low temperature thermal decomposition of glycerol. Currently, there is no known reliable method for measuring acrolein in sources. Acrolein and emissions of other volatile organic compounds were characterized through the use of a SUMMA

Neuroprotective role of hydralazine in rat spinal cord injury-attenuation of acrolein-mediated damage.

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Park, Jonghyuck; Zheng, Lingxing; Marquis, Andrew; Walls, Michael; Duerstock, Brad; Pond, Amber; Vega-Alvarez, Sasha; Wang, He; Ouyang, Zheng; Shi, Riyi

2014-04-01

Acrolein, an α,β-unsaturated aldehyde and a reactive product of lipid peroxidation, has been suggested as a key factor in neural post-traumatic secondary injury in spinal cord injury (SCI), mainly based on in vitro and ex vivo evidence. Here, we demonstrate an increase of acrolein up to 300%; the elevation lasted at least 2 weeks in a rat SCI model. More importantly, hydralazine, a known acrolein scavenger can provide neuroprotection when applied systemically. Besides effectively reducing acrolein, hydralazine treatment also resulted in significant amelioration of tissue damage, motor deficits, and neuropathic pain. This effect was further supported by demonstrating the ability of hydralazine to reach spinal cord tissue at a therapeutic level following intraperitoneal application. This suggests that hydralazine is an effective neuroprotective agent not only in vitro, but in a live animal model of SCI as well. Finally, the role of acrolein in SCI was further validated by the fact that acrolein injection into the spinal cord caused significant SCI-like tissue damage and motor deficits. Taken together, available evidence strongly suggests a critical causal role of acrolein in the pathogenesis of spinal cord trauma. Since acrolein has been linked to a variety of illness and conditions, we believe that acrolein-scavenging measures have the potential to be expanded significantly ensuring a broad impact on human health. © 2013 International Society for Neurochemistry.

Neuroprotective role of hydralazine in rat spinal cord injury-attenuation of acrolein-mediated damage

Science.gov (United States)

Park, Jonghyuck; Zheng, Lingxing; Marquis, Andrew; Walls, Michael; Duerstock, Brad; Pond, Amber; Alvarez, Sascha Vega; He, Wang; Ouyang, Zheng; Shi, Riyi

2014-01-01

Acrolein, an α,β-unsaturated aldehyde and a reactive product of lipid peroxidation, has been suggested as a key factor in neural post-traumatic secondary injury in SCI, mainly based on in vitro and ex vivo evidence. Here we demonstrate an increase of acrolein up to 300%; the elevation lasted at least two weeks in a rat SCI model. More importantly, hydralazine, a known acrolein scavenger can provide neuroprotection when applied systemically. Besides effectively reducing acrolein, hydralazine treatment also resulted in significant amelioration of tissue damage, motor deficits, and neuropathic pain. This effect was further supported by demonstrating the ability of hydralazine to reach spinal cord tissue at a therapeutic level following intraperitoneal application. This suggests that hydralazine is an effective neuroprotective agent not only in vitro, but in a live animal model of SCI as well. Finally, the role of acrolein in SCI was further validated by the fact that acrolein injection into the spinal cord caused significant SCI-like tissue damage and motor deficits. Taken together, available evidence strongly suggests a critical causal role of acrolein in the pathogenesis of spinal cord trauma. Since acrolein has been linked to a variety of illness and conditions, we believe that acrolein-scavenging measures have the potential to be expanded significantly ensuring a broad impact on human health. PMID:24286176

Critical role of acrolein in secondary injury following ex vivo spinal cord trauma.

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Hamann, Kristin; Durkes, Abigail; Ouyang, Hui; Uchida, Koji; Pond, Amber; Shi, Riyi

2008-11-01

The pathophysiology of spinal cord injury (SCI) is characterized by the initial, primary injury followed by secondary injury processes in which oxidative stress is a critical component. Secondary injury processes not only exacerbate pathology at the site of primary injury, but also result in spreading of injuries to the adjacent, otherwise healthy tissue. The lipid peroxidation byproduct acrolein has been implicated as one potential mediator of secondary injury. To further and rigorously elucidate the role of acrolein in secondary injury, a unique ex vivo model is utilized to isolate the detrimental effects of mechanical injury from toxins such as acrolein that are produced endogenously following SCI. We demonstrate that (i) acrolein-Lys adducts are capable of diffusing from compressed tissue to adjacent, otherwise uninjured tissue; (ii) secondary injury by itself produces significant membrane damage and increased superoxide production; and (iii) these injuries are significantly attenuated by the acrolein scavenger hydralazine. Furthermore, hydralazine treatment results in significantly less membrane damage 2 h following compression injury, but not immediately after. These findings support our hypothesis that, following SCI, acrolein is increased to pathologic concentrations, contributes significantly to secondary injury, and thus represents a novel target for scavenging to promote improved recovery.

Determination of Urine 3-HPMA, a Stable Acrolein Metabolite in a Rat Model of Spinal Cord Injury

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Zheng, Lingxing; Park, Jonghyuck; Walls, Michael; Tully, Melissa; Jannasch, Amber; Cooper, Bruce

2013-01-01

Abstract Acrolein has been suggested to be involved in a variety of pathological conditions. The monitoring of acrolein is of significant importance in delineating the pathogenesis of various diseases. Aimed at overcoming the reactivity and volatility of acrolein, we describe a specific and stable metabolite of acrolein in urine, N-acetyl-S-3-hydroxypropylcysteine (3-HPMA), as a potential surrogate marker for acrolein quantification. Using the LC/MS/MS method, we demonstrated that 3-HPMA was significantly elevated in a dose-dependent manner when acrolein was injected into rats IP or directly into the spinal cord, but not when acrolein scavengers were co-incubated with acrolein solution. A nonlinear mathematic relationship is established between acrolein injected directly into the spinal cord and a correlated dose-dependent increase of 3-HPMA, suggesting the increase of 3-HPMA becomes less apparent as the level of injected acrolein increases. The elevation of 3-HPMA was further detected in the rat spinal cord injury, a pathological condition known to be associated with elevated endogenous acrolein. This finding was further validated by concomitant confirmation of increased acrolein-lysine adducts using established dot immunoblotting techniques. The noninvasive nature of measuring 3-HPMA concentrations in urine allows for long-term monitoring of acrolein in the same animal and ultimately in human clinical studies. Due to wide spread involvement of acrolein in human health, the benefits of this study have the potential to enhance human health significantly. PMID:23697633

Molecular Binding Contributes to Concentration Dependent Acrolein Deposition in Rat Upper Airways: CFD and Molecular Dynamics Analyses

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Jinxiang Xi

2018-03-01

Full Text Available Existing in vivo experiments show significantly decreased acrolein uptake in rats with increasing inhaled acrolein concentrations. Considering that high-polarity chemicals are prone to bond with each other, it is hypothesized that molecular binding between acrolein and water will contribute to the experimentally observed deposition decrease by decreasing the effective diffusivity. The objective of this study is to quantify the probability of molecular binding for acrolein, as well as its effects on acrolein deposition, using multiscale simulations. An image-based rat airway geometry was used to predict the transport and deposition of acrolein using the chemical species model. The low Reynolds number turbulence model was used to simulate the airflows. Molecular dynamic (MD simulations were used to study the molecular binding of acrolein in different media and at different acrolein concentrations. MD results show that significant molecular binding can happen between acrolein and water molecules in human and rat airways. With 72 acrolein embedded in 800 water molecules, about 48% of acrolein compounds contain one hydrogen bond and 10% contain two hydrogen bonds, which agreed favorably with previous MD results. The percentage of hydrogen-bonded acrolein compounds is higher at higher acrolein concentrations or in a medium with higher polarity. Computational dosimetry results show that the size increase caused by the molecular binding reduces the effective diffusivity of acrolein and lowers the chemical deposition onto the airway surfaces. This result is consistent with the experimentally observed deposition decrease at higher concentrations. However, this size increase can only explain part of the concentration-dependent variation of the acrolein uptake and acts as a concurrent mechanism with the uptake-limiting tissue ration rate. Intermolecular interactions and associated variation in diffusivity should be considered in future dosimetry modeling of

Molecular Binding Contributes to Concentration Dependent Acrolein Deposition in Rat Upper Airways: CFD and Molecular Dynamics Analyses.

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Xi, Jinxiang; Hu, Qin; Zhao, Linlin; Si, Xiuhua April

2018-03-27

Existing in vivo experiments show significantly decreased acrolein uptake in rats with increasing inhaled acrolein concentrations. Considering that high-polarity chemicals are prone to bond with each other, it is hypothesized that molecular binding between acrolein and water will contribute to the experimentally observed deposition decrease by decreasing the effective diffusivity. The objective of this study is to quantify the probability of molecular binding for acrolein, as well as its effects on acrolein deposition, using multiscale simulations. An image-based rat airway geometry was used to predict the transport and deposition of acrolein using the chemical species model. The low Reynolds number turbulence model was used to simulate the airflows. Molecular dynamic (MD) simulations were used to study the molecular binding of acrolein in different media and at different acrolein concentrations. MD results show that significant molecular binding can happen between acrolein and water molecules in human and rat airways. With 72 acrolein embedded in 800 water molecules, about 48% of acrolein compounds contain one hydrogen bond and 10% contain two hydrogen bonds, which agreed favorably with previous MD results. The percentage of hydrogen-bonded acrolein compounds is higher at higher acrolein concentrations or in a medium with higher polarity. Computational dosimetry results show that the size increase caused by the molecular binding reduces the effective diffusivity of acrolein and lowers the chemical deposition onto the airway surfaces. This result is consistent with the experimentally observed deposition decrease at higher concentrations. However, this size increase can only explain part of the concentration-dependent variation of the acrolein uptake and acts as a concurrent mechanism with the uptake-limiting tissue ration rate. Intermolecular interactions and associated variation in diffusivity should be considered in future dosimetry modeling of high

Redox mechanism of neurotoxicity by a serotonin-acrolein polymeric melanoid.

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Murphy, Meghan M; Miller, Elizabeth D; Fibuch, Eugene E; Seidler, Norbert W

2011-02-01

Postoperative cognitive dysfunction may be associated with the toxic products of lipid peroxidation, such as the α,β-unsaturated aldehyde acrolein, which accumulates in aging. We previously identified an acrolein-mediated, serotonin-derived melanoid product, or SDM. This study further characterizes this putative novel neuromelanin, which is not made from catecholamines. In addition to its strong protein-binding properties, we observed that SDM binds Fe(2+) readily and exhibits complex redox characteristics. SDM may exist as a two-dimensional network of polymers that coalesce into larger entities exhibiting electroactive properties. These observations suggest that SDM may contribute to the decline in cognition due to focal degeneration from SDM-mediated free-radical production. We know that inhalational anesthetics sequester acrolein, which is toxic to neurons, and we propose that the local increase in acrolein depletes serotonin levels and enhances neuronal vulnerability through the production of neuromelanin-like structures, such as SDM.

Acrolein inhalation prevents VEGF-induced mobilization of Flk-1+/Sca-1+ cells in mice

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Wheat, Laura A.; Haberzettl, Petra; Hellmann, Jason; Baba, Shahid P.; Bertke, Matthew; Lee, Jongmin; McCracken, James; O’Toole, Timothy E.; Bhatnagar, Aruni; Conklin, Daniel J.

2011-01-01

Objectives Acrolein is a toxic chemical present in tobacco, wood and coal smoke as well as automobile exhaust. Because exposure to these pollutants is associated with an increase in cardiovascular disease risk, we studied the effects of acrolein on Flk-1+/Sca-1+ cells that are involved in vascular repair. Methods and Results In adult male C57BL/6 mice, inhalation of acrolein (1ppm, 6h/day, 4 days or 5ppm for 2 or 6h) led to the formation of protein-acrolein adducts in the bone marrow and diminished levels of plasma NOx and circulating Flk-1+/Sca-1+ but not Sca-1+ only cells. Acrolein exposure increased the number of apoptotic Flk-1+/Sca1+ cells in circulation, and increased bone marrow-derived cells with endothelial characteristics (Dil-acLDL/UE-lectin and Flk-1+/Sca-1+) in culture. Deficits in the circulating levels of Flk-1+/Sca-1+ cells were reversed after 7 days of recovery in acrolein-free air. Exposure to acrolein blocked VEGF/AMD3100-stimulated mobilization of Flk-1+/Sca-1+ but not Sca-1+ only cells and prevented VEGF-induced phosphorylation of Akt and eNOS in the aorta. Conclusions Inhalation of acrolein increases apoptosis and suppresses the circulating levels of Flk-1+/Sca-1+ cells, while increasing these cells in the bone marrow and preventing their mobilization by VEGF. Exposure to acrolein-rich pollutants could impair vascular repair capacity. PMID:21527748

Effects of maternal acrolein exposure during pregnancy on testicular testosterone production in fetal rats

OpenAIRE

Yang, Yuzhuo; Zhang, Zhe; Zhang, Hongliang; Hong, Kai; Tang, Wenhao; Zhao, Lianming; Lin, Haocheng; Liu, Defeng; Mao, Jiaming; Wu, Han; Jiang, Hui

2017-01-01

Acrolein has been reported to have diverse toxic effects on various organs, including the reproductive system. However, little is known regarding the effects of maternal acrolein exposure on testicular steroidogenesis in male offspring. The present study investigated the effects of acrolein on fetal testosterone production and associated genes. Pregnant Sprague-Dawley rats were intraperitoneally injected with vehicle (normal saline) or 1, 2 or 5 mg/kg acrolein from gestational day (GD) 14?20,...

Effect of acrolein, a hazardous air pollutant in smoke, on human middle ear epithelial cells.

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Song, Jae-Jun; Lee, Jong Dae; Lee, Byung Don; Chae, Sung Won; Park, Moo Kyun

2013-10-01

Acrolein is a hazardous air pollutant. Tobacco smoke and indoor air pollution are the main causes of human exposure. Acrolein has been shown to cause cytotoxicity in the airways and induce inflammation and mucin production in pulmonary cells. We investigated whether acrolein caused cytotoxicity, induced inflammation or increased expression of mucin in immortalized human middle ear epithelial cell lines (HMEECs). Cytotoxicity following acrolein treatment was investigated using the MTT assay, flow cytometry, and Hoechst 33342 staining of HMEECs. We measured expression of inflammatory cytokines tumor necrosis factor (TNF)-α and cyclo-oxygenase (COX)-2 and the mucin gene MUC5AC using semi-quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting. Exposure to >50 μg/mL acrolein caused a decrease in cell viability. Acrolein induced apoptosis and necrosis at 50 μg/mL. Acrolein at 5-50 μg/mL increased expression of TNF-α and COX-2, as shown by RT-PCR and Western blotting. Acrolein exposure at 5-50 μg/mL for 2-24h increased MUC5AC expression, as determined by RT-PCR. Acrolein decreased cell viability, induced an inflammatory response, and increased mucin gene expression in HMEECs. These findings support the hypothesis that acrolein, a hazardous air pollutant in tobacco smoke and ambient air, is a risk factor for otitis media. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Multitarget trehalose-carnosine conjugates inhibit Aβ aggregation, tune copper(II) activity and decrease acrolein toxicity.

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Grasso, Giuseppa Ida; Bellia, Francesco; Arena, Giuseppe; Satriano, Cristina; Vecchio, Graziella; Rizzarelli, Enrico

2017-07-28

Increasing evidence is accumulating, showing that neurodegenerative disorders are somehow associated with the toxicity of amyloid aggregates, metal ion dyshomeostasis as well as with products generated by oxidative stress. Within the biological oxidation products, acrolein does have a prominent role. A promising strategy to deal with the above neurogenerative disorders is to use multi-functions bio-molecules. Herein, we show how a class of bio-conjugates takes advantage of the antiaggregating, antioxidant and antiglycating properties of trehalose and carnosine. Their ability to sequester acrolein and to inhibit both self- and metal-induced aggregation is here reported. The copper(II) coordination properties of a new trehalose-carnosine conjugate and the relative antioxidant effects have also been investigated. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Acrolein scavengers, cysteamine and N-benzylhydroxylamine, reduces the mouse liver damage after acetaminophen overdose.

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Koyama, Ryo; Mizuta, Ryushin

2017-01-10

Our previous study suggested that the highly toxic α,β-unsaturated aldehyde acrolein, a byproduct of oxidative stress, plays a major role in acetaminophen-induced liver injury. In this study, to determine the involvement of acrolein in the liver injury and to identify novel therapeutic options for the liver damage, we examined two putative acrolein scavengers, a thiol compound cysteamine and a hydroxylamine N-benzylhydroxylamine, in cell culture and in mice. Our results showed that cysteamine and N-benzylhydroxylamine effectively prevented the cell toxicity of acrolein in vitro and acetaminophen-induced liver injury in vivo, which suggested that acrolein is involved in the liver damage, and these two drugs can be potential therapeutic options for this condition.

Influence of Catalyst Acid/Base Properties in Acrolein Production by Oxidative Coupling of Ethanol and Methanol.

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Lilić, Aleksandra; Bennici, Simona; Devaux, Jean-François; Dubois, Jean-Luc; Auroux, Aline

2017-05-09

Oxidative coupling of methanol and ethanol represents a new route to produce acrolein. In this work, the overall reaction was decoupled in two steps, the oxidation and the aldolization, by using two consecutive reactors to investigate the role of the acid/base properties of silica-supported oxide catalysts. The oxidation of a mixture of methanol and ethanol to formaldehyde and acetaldehyde was performed over a FeMoO x catalyst, and then the product mixture was transferred without intermediate separation to a second reactor, in which the aldol condensation and dehydration to acrolein were performed over the supported oxides. The impact of the acid/base properties on the selectivity towards acrolein was investigated under oxidizing conditions for the first time. The acid/base properties of the catalysts were investigated by NH 3 -, SO 2 -, and methanol-adsorption microcalorimetry. A MgO/SiO 2 catalyst was the most active in acrolein production owing to an appropriate ratio of basic to acidic sites. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Acrolein involvement in sensory and behavioral hypersensitivity following spinal cord injury in the rat

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Zheng, Lingxing; Walls, Michael; Allette, Yohance M.; White, Fletcher A.; Shi, Riyi

2013-01-01

Growing evidence suggests that oxidative stress, as associated with spinal cord injury (SCI), may play a critical role in both neuroinflammation and neuropathic pain conditions. The production of the endogenous aldehyde acrolein, following lipid peroxidation during the inflammatory response, may contribute to peripheral sensitization and hyperreflexia following SCI via the TRPA1-dependent mechanism. Here we report that there are enhanced levels of acrolein and increased neuronal sensitivity to the aldehyde for at least 14 days after SCI. Concurrent with injury-induced increases in acrolein concentration is an increased expression of TRPA1 in the lumbar (L3-L6) sensory ganglia. As proof of the potential pronociceptive role for acrolein, intrathecal injections of acrolein revealed enhanced sensitivity to both tactile and thermal stimuli for up to 10 days, supporting the compound’s pro-nociceptive functionality. Treatment of SCI animals with the acrolein scavenger hydralazine produced moderate improvement in tactile responses as well as robust changes in thermal sensitivity for up to 49 days. Taken together, these data suggests that acrolein directly modulates SCI-associated pain behavior, making it a novel therapeutic target for preclinical and clinical SCI as an analgesic. PMID:24147766

Studies on the polymerization of acrolein oxime, 6

International Nuclear Information System (INIS)

Masuda, Seizo; Tamai, Harumi; Ota, Tadatoshi; Torii, Munetomo; Tanaka, Masami.

1979-01-01

Radiation-induced polymerization and copolymerization of acrolein oxime are investigated in different solvents and at a wide range of temperature for obtaining information on the reaction mechanism. Acrolein oxime is polymerized ionically, irrespective of dryness of the sample. Arrhenius plots for the polymerization rate, which do not yield a linear relation, can be adequately approximated by two straight lines. An anionic mechanism is operative above the room temperature, while a cationic mechanism predominates below -23 0 C. The reaction in the intermediate temperature range proceeds by a competitive mechanism, and the rate of the anionic and cationic polymerizations becomes equal at the temperature near -5 0 C. The reaction rate is proportional to the square root of dose rate at room temperature and -23 0 C. On the basis of these data, it is proposed that the polymerization of acrolein oxime by γ-irradiation proceeds by free-ionic mechanisms. (author)

The active component of vanadium-molybdenum catalysts for the oxidation of acrolein to acrylic acid

International Nuclear Information System (INIS)

Andrushkevich, T.V.; Kuznetsova, T.G.

1986-01-01

The catalytic properties of the vanadium-molybdenum oxide system were investigated in the oxidation of acrolein to acrylic acid. The active component of the catalyst is the compound VMo 3 O 11 , the maximum amount of which is observed at a content of 7-15 mole% V 2 O 4 . The compound VMo 3 O 11 is formed in the thermodecomposition of silicomolybdovanadium heteropoly acids or isopoly compounds, reduced with respect to vanadium, and contains V 4+ and Mo 6+ . The optimum treatment for the formation of this compound is treatment in the reaction mixture at 400 degrees C

Evaluation of dementia by acrolein, amyloid-β and creatinine.

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Igarashi, Kazuei; Yoshida, Madoka; Waragai, Masaaki; Kashiwagi, Keiko

2015-10-23

Plasma, urine and cerebrospinal fluid (CSF) were examined for biochemical markers of dementia. Protein-conjugated acrolein (PC-Acro) and the amyloid-β (Aβ)40/42 ratio in plasma can be used to detect mild cognitive impairment (MCI) and Alzheimer's disease (AD). In plasma, PC-Acro and the Aβ40/42 ratio in MCI and AD were significantly higher relative to non-demented subjects. Furthermore, urine acrolein metabolite, 3-hydroxypropyl mercapturic acid (3-HPMA)/creatinine (Cre) and amino acid-conjugated acrolein (AC-Acro)/Cre in AD were significantly lower than MCI. It was also shown that reduced urine 3-HPMA/Cre correlated with increased plasma Aβ40/42 ratio in dementia. The Aβ40/PC-Acro ratio in CSF, together with Aβ40 and Aβ40/42 ratio, was lower in AD than MCI. Increased plasma PC-Acro and Aβ40/42 ratio and decreased urine 3-HPMA/Cre correlated with cognitive ability (MMSE). These results indicate that the measurements of acrolein derivatives together with Aβ and Cre in biologic fluids is useful to estimate severity of dementia. Copyright © 2015 Elsevier B.V. All rights reserved.

Reductive detoxification of acrolein as a potential role for aldehyde reductase (AKR1A) in mammals.

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Kurahashi, Toshihiro; Kwon, Myoungsu; Homma, Takujiro; Saito, Yuka; Lee, Jaeyong; Takahashi, Motoko; Yamada, Ken-Ichi; Miyata, Satoshi; Fujii, Junichi

2014-09-12

Aldehyde reductase (AKR1A), a member of the aldo-keto reductase superfamily, suppresses diabetic complications via a reduction in metabolic intermediates; it also plays a role in ascorbic acid biosynthesis in mice. Because primates cannot synthesize ascorbic acid, a principle role of AKR1A appears to be the reductive detoxification of aldehydes. In this study, we isolated and immortalized mouse embryonic fibroblasts (MEFs) from wild-type (WT) and human Akr1a-transgenic (Tg) mice and used them to investigate the potential roles of AKR1A under culture conditions. Tg MEFs showed higher methylglyoxal- and acrolein-reducing activities than WT MEFs and also were more resistant to cytotoxicity. Enzymatic analyses of purified rat AKR1A showed that the efficiency of the acrolein reduction was about 20% that of glyceraldehyde. Ascorbic acid levels were quite low in the MEFs, and while the administration of ascorbic acid to the cells increased the intracellular levels of ascorbic acid, it had no affect on the resistance to acrolein. Endoplasmic reticulum stress and protein carbonylation induced by acrolein treatment were less evident in Tg MEFs than in WT MEFs. These data collectively indicate that one of the principle roles of AKR1A in primates is the reductive detoxification of aldehydes, notably acrolein, and protection from its detrimental effects. Copyright © 2014 Elsevier Inc. All rights reserved.

Effects of maternal acrolein exposure during pregnancy on testicular testosterone production in fetal rats.

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Yang, Yuzhuo; Zhang, Zhe; Zhang, Hongliang; Hong, Kai; Tang, Wenhao; Zhao, Lianming; Lin, Haocheng; Liu, Defeng; Mao, Jiaming; Wu, Han; Jiang, Hui

2017-07-01

Acrolein has been reported to have diverse toxic effects on various organs, including the reproductive system. However, little is known regarding the effects of maternal acrolein exposure on testicular steroidogenesis in male offspring. The present study investigated the effects of acrolein on fetal testosterone production and associated genes. Pregnant Sprague‑Dawley rats were intraperitoneally injected with vehicle (normal saline) or 1, 2 or 5 mg/kg acrolein from gestational day (GD) 14‑20, and fetal testes were examined on GD 21. Fetal body and testicular weights were markedly reduced in pups following exposure to high doses of acrolein (5 mg/kg) in late pregnancy. Notably, in utero exposure of 5 mg/kg acrolein significantly decreased the testicular testosterone level and downregulated the expression levels of steroidogenic acute regulatory protein (StAR) and 3β‑hydroxysteroid dehydrogenase (3β‑HSD), whereas the levels of other steroidogenic enzymes, including scavenger receptor class B, cholesterol side‑chain cleavage enzyme and steroid 17 alpha‑hydroxylase/17,20 lyase, were unaffected. Furthermore, the 3β‑HSD immunoreactive area in the interstitial region of the fetal testes was reduced at a 5 mg/kg dose, whereas the protein expression levels of 4‑hydroxynonenalwere dose‑dependently increased following maternal exposure to acrolein. mRNA expression levels of insulin‑like factor 3, a critical gene involved in testicular descent, were unaltered following maternal acrolein exposure. Taken together, the results of the present study suggested that maternal exposure to high doses of acrolein inhibited fetal testosterone synthesis, and abnormal expression of StAR and 3β‑HSD may be associated with impairment of the steroidogenic capacity.

Inhibition of acrolein-stimulated MUC5AC production by fucoidan in human bronchial epithelial cells.

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Pokharel, Yuba Raj; Yoon, Se Young; Kim, Sang Kyum; Li, Jian-Dong; Kang, Keon Wook

2008-10-01

Fucoidan, a marine sulfated polysaccharide has both antithrombotic and anti-inflammatory effects. We determined the effect of fucoidan on MUC5AC expression in a human bronchial epithelial cell line, NCI-H292. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that fucoidan inhibited MUC5AC expression and protein secretion in cells stimulated with acrolein, a toxic aldehyde present in tobacco smoke. The activation of both nuclear factor-kappa B (NF-kappa B) and activator protein 1 (AP-1) are key steps in the transcriptional activation of MUC5AC. We found that the acrolein-mediated transactivation of MUC5AC was selectively dependent on AP-1 activation and was suppressed by fucoidan. Fucoidan-induced AP-1 inhibition and MUC5AC repression might be associated with fucoidan's protective effects against respiratory diseases.

Gut Microbial Glycerol Metabolism as an Endogenous Acrolein Source

OpenAIRE

Zhang, Jianbo; Sturla, Shana; Lacroix, Christophe; Schwab, Clarissa

2018-01-01

ABSTRACT Acrolein is a highly reactive electrophile causing toxic effects, such as DNA and protein adduction, oxidative stress, endoplasmic reticulum stress, immune dysfunction, and membrane damage. This Opinion/Hypothesis provides an overview of endogenous and exogenous acrolein sources, acrolein’s mode of action, and its metabolic fate. Recent reports underpin the finding that gut microbial glycerol metabolism leading to the formation of reuterin is an additional source of endogenous acrole...

Determination of Urine 3-HPMA, a Stable Acrolein Metabolite in a Rat Model of Spinal Cord Injury

OpenAIRE

Zheng, Lingxing; Park, Jonghyuck; Walls, Michael; Tully, Melissa; Jannasch, Amber; Cooper, Bruce; Shi, Riyi

2013-01-01

Acrolein has been suggested to be involved in a variety of pathological conditions. The monitoring of acrolein is of significant importance in delineating the pathogenesis of various diseases. Aimed at overcoming the reactivity and volatility of acrolein, we describe a specific and stable metabolite of acrolein in urine, N-acetyl-S-3-hydroxypropylcysteine (3-HPMA), as a potential surrogate marker for acrolein quantification. Using the LC/MS/MS method, we demonstrated that 3-HPMA was significa...

Aggravation of brain infarction through an increase in acrolein production and a decrease in glutathione with aging.

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Uemura, Takeshi; Watanabe, Kenta; Ishibashi, Misaki; Saiki, Ryotaro; Kuni, Kyoshiro; Nishimura, Kazuhiro; Toida, Toshihiko; Kashiwagi, Keiko; Igarashi, Kazuei

2016-04-29

We previously reported that tissue damage during brain infarction was mainly caused by inactivation of proteins by acrolein. This time, it was tested why brain infarction increases in parallel with aging. A mouse model of photochemically induced thrombosis (PIT) was studied using 2, 6, and 12 month-old female C57BL/6 mice. The size of brain infarction in the mouse PIT model increased with aging. The volume of brain infarction in 12 month-old mice was approximately 2-fold larger than that in 2 month-old mice. The larger brain infarction in 12 month-old mice was due to an increase in acrolein based on an increase in the activity of spermine oxidase, together with a decrease in glutathione (GSH), a major acrolein-detoxifying compound in cells, based on the decrease in one of the subunits of glutathione biosynthesizing enzymes, γ-glutamylcysteine ligase modifier subunit, with aging. The results indicate that aggravation of brain infarction with aging was mainly due to the increase in acrolein production and the decrease in GSH in brain. Copyright © 2016 Elsevier Inc. All rights reserved.

Catalytic Dehydration of Glycerol to Acrolein over a Catalyst of Pd/LaY Zeolite and Comparison with the Chemical Equilibrium

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Israel Pala Rosas

2017-02-01

Full Text Available Glycerol dehydration to acrolein was studied with three catalysts using zeolite-Y. This zeolite in its protonic form (HY, with La (LaY and Pd with La (Pd/LaY, was characterized by X-ray diffraction (XRD, Fourier-transform-infrared spectroscopy (FTIR with pyridine, BET, Scanning Electron Microscope (SEM–Energy-Dispersive Spectroscopy X-ray (EDS and the catalytic activity tests were carried out under H2 atmosphere. It was found that La ions exchanged in the zeolite-Y resulted in the improvement of both glycerol conversion and yield to acrolein, also a relatively constant glycerol conversion was achieved up to three hours, due to the presence of Pd on the catalyst and H2 in the feed. The comparison of the calculated and experimental yields obtained from the catalytic tests of the Pd/LaY catalyst indicates a greater activity for the reaction to acrolein than for the reaction to acetol. The calculated equilibrium yields of the dehydration reaction from glycerol to acrolein, acetol, ethanal, methanol, and water and the experimental yields of a Pd/LaY catalyst were compared. Thermodynamically, a complete conversion of glycerol can be achieved since the general system remains exothermic and promotes the path to acetol below 480 K. Above this temperature the system consumes energy and favors the production of acrolein, reaching its maximum concentration at 600 K.

Acrolein in cigarette smoke inhibits T-cell responses.

Science.gov (United States)

Lambert, Cherie; McCue, Jesica; Portas, Mary; Ouyang, Yanli; Li, JiMei; Rosano, Thomas G; Lazis, Alexander; Freed, Brian M

2005-10-01

Cigarette smoking inhibits T-cell responses in the lungs, but the immunosuppressive compounds have not been fully identified. Cigarette smoke extracts inhibit IL-2, IFN-gamma, and TNF-alpha production in stimulated lymphocytes obtained from peripheral blood, even when the extracts were diluted 100-fold to 1000-fold. The objective of these studies was to identify the immunosuppressive compounds found in cigarette smoke. Gas chromatography/mass spectroscopy and HPLC were used to identify and quantitate volatile compounds found in cigarette smoke extracts. Bioactivity was measured by viability and production of cytokine mRNA and protein levels in treated human lymphocytes. The vapor phase of the cigarette smoke extract inhibited cytokine production, indicating that the immunosuppressive compounds were volatile. Among the volatile compounds identified in cigarette smoke extracts, only the alpha,beta-unsaturated aldehydes, acrolein (inhibitory concentration of 50% [IC50] = 3 micromol/L) and crotonaldehyde (IC50 = 6 micromol/L), exhibited significant inhibition of cytokine production. Although the levels of aldehydes varied 10-fold between high-tar (Camel) and ultralow-tar (Carlton) extracts, even ultralow-tar cigarettes produced sufficient levels of acrolein (34 micromol/L) to suppress cytokine production by >95%. We determined that the cigarette smoke extract inhibited transcription of cytokine genes. The inhibitory effects of acrolein could be blocked with the thiol compound N-acetylcysteine. The vapor phase from cigarette smoke extracts potently suppresses cytokine production. The compound responsible for this inhibition appears to be acrolein.

Effects of Acrolein on Leukotriene Biosynthesis in Human Neutrophils

OpenAIRE

Zemski Berry, Karin A.; Henson, Peter M.; Murphy, Robert C.

2008-01-01

Acrolein is a toxic, highly reactive α,β-unsaturated aldehyde that is present in high concentrations in cigarette smoke. In the current study, the effect of acrolein on eicosanoid synthesis in stimulated human neutrophils was examined. Eicosanoid synthesis in neutrophils was initiated by priming with granulocyte-macrophage colony-stimulating factor (GM-CSF) and subsequent stimulation with formyl-methionyl-leucyl-phenylalanine (fMLP) and 5-LO products in addition to small amounts of COX produc...

Acrolein Yields in Mainstream Smoke From Commercial Cigarette and Little Cigar Tobacco Products.

Science.gov (United States)

Cecil, Todd L; Brewer, Tim M; Young, Mimy; Holman, Matthew R

2017-07-01

Many carbonyls are produced from the combustion of tobacco products and many of these carbonyls are harmful or potentially harmful constituents of mainstream cigarette smoke. One carbonyl of particular interest is acrolein, which is formed from the incomplete combustion of organic matter and the most significant contributor to non-cancer respiratory effects from cigarette smoke. Sheet-wrapped cigars, also known as "little cigars," are a type of tobacco products that have not been extensively investigated in literature. This study uses standard cigarette testing protocols to determine the acrolein yields from sheet-wrapped cigars. Sheet-wrapped cigar and cigarette products were tested by derivatizing the mainstream smoke with 2,4-dinitrophenylhydrazine (DNPH) solution and then quantifying the derivatives using conventional analytical systems. The results demonstrate that sheet-wrapped cigars can be tested for acrolein yields in mainstream smoke using the same methods used for the evaluation of cigarettes. The variability in the sheet-wrapped cigars and cigarettes under the International Organization for Standardization smoking regimen is statistically similar at the 95% confidence interval; however, increased variability is observed for sheet-wrapped cigar products under the Health Canada Intense (CI) smoking regimen. The amount of acrolein released by smoking sheet-wrapped cigars can be measured using standard smoking regimen currently used for cigarettes. The sheet-wrapped cigars were determined to yield similar quantity of acrolein from commercial cigarette products using two standard smoking regimens. This article reports on the measured quantity of acrolein from 15 commercial sheet-wrapped cigars using a validated standard smoking test method that derivatizes acrolein in the mainstream smoke with DNPH solution, and uses Liquid Chromatography/Ultra-Violet Detection (LC/UV) for separation and detection. These acrolein yields were similar to the levels found in

IRIS TOXICOLOGICAL REVIEW AND SUMMARY DOCUMENTS FOR ACROLEIN (EXTERNAL REVIEW DRAFT)

Science.gov (United States)

Acrolein is a colorless to yellowish flammable liquid with a disagreeable, choking odor. The principal use of acrolein is as an intermediate in the synthesis of acrylic acid, which is used to make acrylates, and of DL-methionine, an essential amino acid used as an animal feed su...

Inhibition by acrolein of light-induced stomatal opening through inhibition of inward-rectifying potassium channels in Arabidopsis thaliana.

Science.gov (United States)

Islam, Md Moshiul; Ye, Wenxiu; Matsushima, Daiki; Khokon, Md Atiqur Rahman; Munemasa, Shintaro; Nakamura, Yoshimasa; Murata, Yoshiyuki

2015-01-01

Acrolein is a reactive α,β-unsaturated aldehyde derived from lipid peroxides, which are produced in plants under a variety of stress. We investigated effects of acrolein on light-induced stomatal opening using Arabidopsis thaliana. Acrolein inhibited light-induced stomatal opening in a dose-dependent manner. Acrolein at 100 μM inhibited plasma membrane inward-rectifying potassium (Kin) channels in guard cells. Acrolein at 100 μM inhibited Kin channel KAT1 expressed in a heterologous system using Xenopus leaves oocytes. These results suggest that acrolein inhibits light-induced stomatal opening through inhibition of Kin channels in guard cells.

Acrolein toxicity involves oxidative stress caused by glutathione depletion in the yeast Saccharomyces cerevisiae.

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Kwolek-Mirek, M; Bednarska, S; Bartosz, G; Biliński, T

2009-08-01

Exposure of yeast cells to allyl alcohol results in intracellular production of acrolein. The toxicity of so formed acrolein involves oxidative stress, as (1) strains deficient in antioxidant defense are hypersensitive to allyl alcohol, (2) exposure to allyl alcohol increases the level of thiobarbituric-acid-reactive substances and decreases glutathione level in the cells, (3) hypoxic and anoxic atmosphere and antioxidants protect against allyl alcohol toxicity, and (4) allyl alcohol causes activation of Yap1p. No increased formation of reactive oxygen species was detected in cells exposed to allyl alcohol, so oxidative stress is due to depletion of cellular thiols and thus alteration in the redox state of yeast cells.

Acute systemic accumulation of acrolein in mice by inhalation at a concentration similar to that in cigarette smoke.

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Tully, Melissa; Zheng, Lingxing; Acosta, Glen; Tian, Ran; Shi, Riyi

2014-12-01

Cigarette smoke is an important environmental factor associated with a wide array of public health concerns. Acrolein, a component of tobacco smoke and a known toxin to various cell types, may be a key pathological factor mediating the adverse effects linked with tobacco smoke. Although acrolein is known to accumulate in the respiratory system after acute nasal exposure, it is not clear if it accumulates systemically, and less is known in the nervous system. The aim of this study was to assess the degree of acrolein accumulation in the circulation and in the spinal cord following acute acrolein inhalation in mice. Using a laboratory-fabricated inhalation chamber, we found elevated urinary 3-HPMA, an acrolein metabolite, and increased acrolein adducts in the spinal cord after weeks of nasal exposure to acrolein at a concentration similar to that in tobacco smoke. The data indicated that acrolein is absorbed into the circulatory system and some enters the nervous system. It is expected that these findings may facilitate further studies to probe the pathological role of acrolein in the nervous system resulting from smoke and other external sources.

Acrolein induces Hsp72 via both PKCdelta/JNK and calcium signaling pathways in human umbilical vein endothelial cells.

Science.gov (United States)

Misonou, Yoshiko; Takahashi, Motoko; Park, Yong Seek; Asahi, Michio; Miyamoto, Yasuhide; Sakiyama, Haruhiko; Cheng, Xinyao; Taniguchi, Naoyuki

2005-05-01

Acrolein is a highly electrophilic alpha,beta-unsaturated aldehydes to which humans are exposed in a variety of environment situations and is also a product of lipid peroxidation. Increased levels of unsaturated aldehydes play an important role in the pathogenesis of a number of human diseases such as Alzheimer's disease, atherosclerosis and diabetes. A number of studies have reported that acrolein evokes downstream signaling via an elevation in cellular oxidative stress. Here, we report that low concentrations of acrolein induce Hsp72 in human umbilical vein endothelial cells (HUVEC) and that both the PKCdelta/JNK pathway and calcium pathway were involved in the induction. The findings confirm that the production of reactive oxygen species (ROS) is not directly involved in the pathway. The induction of Hsp72 was not observed in other cells such as smooth muscle cells (SMC) or COS-1 cells. The results suggest that HUVEC have a unique defense system against cell damage by acrolein in which Hsp72 is induced via activation of both the PKCd/JNK and the calcium pathway.

UTILIZING THE PAKS METHOD FOR MEASURING ACROLEIN AND OTHER ALDEHYDES IN DEARS

Science.gov (United States)

Acrolein is a hazardous air pollutant of high priority due to its high irritation potency and other potential adverse health effects. However, a reliable method is currently unavailable for measuring airborne acrolein at typical environmental levels. In the Detroit Exposure and A...

A cigarette component acrolein induces accelerated senescence in human diploid fibroblast IMR-90 cells.

Science.gov (United States)

Luo, Cheng; Li, Yan; Yang, Liang; Feng, Zhihui; Li, Yuan; Long, Jiangang; Liu, Jiankang

2013-10-01

Cigarette smoking causes various diseases, including lung cancer and cardiovascular disease, and reduces life span, though the mechanisms are not well understood. We hypothesize that smoking may cause cellular mitochondrial dysfunction and oxidative stress, leading to aging acceleration. In the present study, we tested the effects of acrolein, a major representative smoking toxicant, on human lung fibroblast IMR-90 cells with regard to cellular senescence, oxidative stress, and mitochondrial function. The results showed that subacute treatment with low dose of acrolein induces the following events compared to the control cells: cell senescence demonstrated by increases in the activity of β-galactosidase, the higher expression of p53 and p21, decreases in DNA synthesis, Sirt1 expression, and telomere length; oxidative stress occurred as the increases in the production of reactive oxygen species, DNA damage, and protein oxidation; and mitochondrial dysfunction shown as decreases in the mitochondrial membrane potential, mitochondrial biogenesis regulator PGC-1 alpha and mitochondria complex I, II, III, and V. These results suggest that acrolein may accelerate aging through the mechanism of increasing oxidative stress and mitochondrial dysfunction.

Acrolein Inhalation Suppresses Lipopolysaccharide-Induced Inflammatory Cytokine Production but Does Not Affect Acute Airways Neutrophilia1

OpenAIRE

Kasahara, David Itiro; Poynter, Matthew E.; Othman, Ziryan; Hemenway, David; van der Vliet, Albert

2008-01-01

Acrolein is a reactive unsaturated aldehyde that is produced during endogenous oxidative processes and is a major bioactive component of environmental pollutants such as cigarette smoke. Because in vitro studies demonstrate that acrolein can inhibit neutrophil apoptosis, we evaluated the effects of in vivo acrolein exposure on acute lung inflammation induced by LPS. Male C57BL/6J mice received 300 μg/kg intratracheal LPS and were exposed to acrolein (5 parts per million, 6 h/day), either befo...

Acrolein- and 4-Aminobiphenyl-DNA adducts in human bladder mucosa and tumor tissue and their mutagenicity in human urothelial cells.

Science.gov (United States)

Lee, Hyun-Wook; Wang, Hsiang-Tsui; Weng, Mao-wen; Hu, Yu; Chen, Wei-sheng; Chou, David; Liu, Yan; Donin, Nicholas; Huang, William C; Lepor, Herbert; Wu, Xue-Ru; Wang, Hailin; Beland, Frederick A; Tang, Moon-shong

2014-06-15

Tobacco smoke (TS) is a major cause of human bladder cancer (BC). Two components in TS, 4-aminobiphenyl (4-ABP) and acrolein, which also are environmental contaminants, can cause bladder tumor in rat models. Their role in TS related BC has not been forthcoming. To establish the relationship between acrolein and 4-ABP exposure and BC, we analyzed acrolein-deoxyguanosine (dG) and 4-ABP-DNA adducts in normal human urothelial mucosa (NHUM) and bladder tumor tissues (BTT), and measured their mutagenicity in human urothelial cells. We found that the acrolein-dG levels in NHUM and BTT are 10-30 fold higher than 4-ABP-DNA adduct levels and that the acrolein-dG levels in BTT are 2 fold higher than in NHUM. Both acrolein-dG and 4-ABP-DNA adducts are mutagenic; however, the former are 5 fold more mutagenic than the latter. These two types of DNA adducts induce different mutational signatures and spectra. We found that acrolein inhibits nucleotide excision and base excision repair and induces repair protein degradation in urothelial cells. Since acrolein is abundant in TS, inhaled acrolein is excreted into urine and accumulates in the bladder and because acrolein inhibits DNA repair and acrolein-dG DNA adducts are mutagenic, we propose that acrolein is a major bladder carcinogen in TS.

Synthesis of Acrolein from Glycerol Using FePO4 Catalyst in Liquid Phase Dehydration

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Akhmad Zainal Abidin

2016-02-01

Full Text Available Acrolein is currently produced using propylene from crude oil while its price and scarcity are increasing. A renewable material such as glycerol is an attractive alternative for acrolein production. It can be obtained from crude palm oil (CPO and is a byproduct of biodiesel production. Besides being able to compete economically, glycerol is an environmentally friendly material. The purpose of this study is to synthesize acrolein from glycerol using FePO4 catalyst in liquid phase dehydration. The catalyst was prepared by three different methods: hydrothermal (catalyst A, deposition at Fe/P = 1.15 (catalyst B, and deposition at Fe/P = 1.20 (catalyst C. The experimental reaction temperature was varied at 220, 240 and 260 °C under constant atmospheric pressure. The results showed that catalyst C provided the best yield (91%, followed by catalyst A (90% and catalyst B (82%. The increasing reaction temperature showed a tendency to increase the yield of acrolein, while the presence of oxygen reduced the yield of acrolein and allowed the reaction to produce more side products such as glycerol propanal, acetaldehyde, and propionate. Catalyst reuse without any regeneration resulted in a yield profile of acrolein that continued to decline.

Passive Badge Assessment for Long-Term, Low-level Air Monitoring on Submarines: Acrolein Badge Validation

National Research Council Canada - National Science Library

Williams, Kimberly P; Rose-Pehrsson, Susan L; Kidwell, David A

2006-01-01

.... Passive badge monitors for acrolein detection were tested. Long-term sampling efficiency was evaluated for a 28-day period by comparing the response of the passive badge to an active tube sampling method...

Selective Hydrogenation of Acrolein Over Pd Model Catalysts: Temperature and Particle-Size Effects.

Science.gov (United States)

O'Brien, Casey P; Dostert, Karl-Heinz; Schauermann, Swetlana; Freund, Hans-Joachim

2016-10-24

The selectivity in the hydrogenation of acrolein over Fe 3 O 4 -supported Pd nanoparticles has been investigated as a function of nanoparticle size in the 220-270 K temperature range. While Pd(111) shows nearly 100 % selectivity towards the desired hydrogenation of the C=O bond to produce propenol, Pd nanoparticles were found to be much less selective towards this product. In situ detection of surface species by using IR-reflection absorption spectroscopy shows that the selectivity towards propenol critically depends on the formation of an oxopropyl spectator species. While an overlayer of oxopropyl species is effectively formed on Pd(111) turning the surface highly selective for propenol formation, this process is strongly hindered on Pd nanoparticles by acrolein decomposition resulting in CO formation. We show that the extent of acrolein decomposition can be tuned by varying the particle size and the reaction temperature. As a result, significant production of propenol is observed over 12 nm Pd nanoparticles at 250 K, while smaller (4 and 7 nm) nanoparticles did not produce propenol at any of the temperatures investigated. The possible origin of particle-size dependence of propenol formation is discussed. This work demonstrates that the selectivity in the hydrogenation of acrolein is controlled by the relative rates of acrolein partial hydrogenation to oxopropyl surface species and of acrolein decomposition, which has significant implications for rational catalyst design. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Adaptation to acrolein through upregulating the protection by glutathione in human bronchial epithelial cells: the materialization of the hormesis concept.

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Sthijns, Mireille M J P E; Randall, Matthew J; Bast, Aalt; Haenen, Guido R M M

2014-04-18

Acrolein is a thiol reactive compound present in cigarette smoke and plays a pivotal role in the deleterious effects of smoking. Acrolein causes toxicity in human bronchial epithelial cells in a dose dependent manner. GSH forms the first line of defense against acrolein-induced toxicity. At high doses of acrolein (⩾10 μM) the capacity of the cellular protection by GSH is overwhelmed and GSH is not able to quench all the acrolein, resulting in cytotoxicity. At a relatively low dose of acrolein (3 μM), no cytotoxicity is observed due to protection by GSH. Moreover we found that exposure to a low dose of acrolein protects cells against the toxic effect of a second higher dose of acrolein. The adaptation to acrolein is induced via Nrf2 mediated gene expression of γ-glutamylcysteine synthetase leading to elevated GSH levels. This upregulation of the protection by GSH demonstrates a hormetic response to acrolein. Hormesis is an adaptive or compensatory response induced by a relatively subtle challenge of homeostasis by a toxic compound. Insight into the mechanism of hormesis is mandatory for a more accurate societal regulation of toxic compounds. Copyright © 2014 Elsevier Inc. All rights reserved.

Synthesis of Acrolein From Glycerol Using FePO4 Catalyst in Liquid Phase Dehydration

OpenAIRE

Abidin, Akhmad Zainal; Afandi, Rani Guslianti; Graha, Hafis Pratama Rendra

2016-01-01

Acrolein is currently produced using propylene from crude oil while its price and scarcity are increasing. A renewable material such as glycerol is an attractive alternative for acrolein production. It can be obtained from crude palm oil (CPO) and is a byproduct of biodiesel production. Besides being able to compete economically, glycerol is an environmentally friendly material. The purpose of this study is to synthesize acrolein from glycerol using FePO4 catalyst in liquid phase dehydration....

Acrolein stimulates the synthesis of IL-6 and C-reactive protein (CRP) in thrombosis model mice and cultured cells.

Science.gov (United States)

Saiki, Ryotaro; Hayashi, Daisuke; Ikuo, Yukiko; Nishimura, Kazuhiro; Ishii, Itsuko; Kobayashi, Kaoru; Chiba, Kan; Toida, Toshihiko; Kashiwagi, Keiko; Igarashi, Kazuei

2013-12-01

Measurements of protein-conjugated acrolein (PC-Acro), IL-6, and C-reactive protein (CRP) in plasma were useful for identifying silent brain infarction with high sensitivity and specificity. The aim of this study was to determine whether acrolein causes increased production of IL-6 and CRP in thrombosis model mice and cultured cells. In mice with photochemically induced thrombosis, acrolein produced at the locus of infarction increased the level of IL-6 and then CRP in plasma. This was confirmed in cell culture systems - acrolein stimulated the production of IL-6 in mouse neuroblastoma Neuro-2a cells, mouse macrophage-like J774.1 cells, and human umbilical vein endothelial cells (HUVEC), and IL-6 in turn stimulated the production of CRP in human hepatocarcinoma cells. The level of IL-6 mRNA was increased by acrolein through an increase in phosphorylation of the transcription factors, c-Jun, and NF-κB p65. Furthermore, CRP stimulated IL-6 production in mouse macrophage-like J774.1 cells and HUVEC. IL-6 functioned as a protective factor against acrolein toxicity in Neuro-2a cells and HUVEC. These results show that acrolein stimulates the synthesis of IL-6 and CRP, which function as protecting factors against acrolein toxicity, and that the combined measurement of PC-Acro, IL-6, and CRP is effective for identification of silent brain infarction. The combined measurements of protein-conjugated acrolein (PC-Acro), IL-6, and C-reactive protein (CRP) in plasma were useful for identifying silent brain infarction. The aim of this study was to determine whether acrolein causes increased production of IL-6 and CRP, and indeed acrolein increased IL-6 synthesis and IL-6 in turn increased CRP synthesis. Furthermore, IL-6 decreased acrolein toxicity in several cell lines. © 2013 International Society for Neurochemistry.

Time and dose effects of cigarette smoke and acrolein on protein carbonyl formation in HaCaT keratinocytes.

Science.gov (United States)

Avezov, K; Reznick, A Z; Aizenbud, D

2015-01-01

Cigarette smoke (CS) is an important environmental source of human exposure to a highly toxic and chemically active α,β-unsaturated aldehyde: acrolein. It is capable of causing protein carbonylation and dysfunction, especially in oral tissues of smokers, constantly exposed to CS toxic constituents. The foremost damage is considered to be cumulative, but even a short exposure can be potentially harmful. The objectives of the current study were to examine the short time and dose effects of direct CS and acrolein exposure on intracellular protein carbonylation in epithelial cells. HaCaT-keratinocytes were exposed to different doses of acrolein and whole phase CS using a unique smoking simulator apparatus that mimics the exposure in smokers. The rate of intracellular protein carbonyl modification was examined 10-60 min after the exposure by Western blot. In addition, the effect of pre-incubation with a thiol scavenger N-acetylcysteine (NAC) was also assessed. We found that intracellular protein carbonyls increased as fast as 10 min after CS exposure and their concentration doubled after 20 min, with a slight elevation afterwards. Also, carbonyl levels increased gradually as CS and acrolein doses were elevated. Addition of 1 mM NAC neutralized part of the damage. We conclude that CS and acrolein intracellular protein carbonylation is dose- and time- dependent. Even a short time exposure to CS and its aldehydic constituents can be potentially harmful.

Molecular mechanisms of acrolein-mediated myelin destruction in CNS trauma and disease

Science.gov (United States)

Shi, Riyi; Page, Jessica; Tully, Melissa

2016-01-01

Myelin is a critical component of the nervous system facilitating efficient propagation of electrical signals and thus communication between the central and peripheral nervous systems and organ systems they innervate throughout the body. In instances of neurotrauma and neurodegenerative disease, injury to myelin is a prominent pathological feature responsible for conduction deficits and leaves axons vulnerable to damage from noxious compounds. Although the pathological mechanisms underlying myelin loss have yet to be fully characterized, oxidative stress appears to play a prominent role. Specifically, acrolein, a neurotoxic aldehyde that is both a product and instigator of oxidative stress, has been observed in studies to elicit demyelination through calcium-independent and -dependent mechanisms and also by affecting glutamate uptake and promoting excitotoxicity. Furthermore, pharmacological scavenging of acrolein has demonstrated a neuroprotective effect in animal disease models by conserving myelin structural integrity and alleviating functional deficits. This evidence is indicative that acrolein may be a key culprit of myelin damage while acrolein scavenging could potentially be a promising therapeutic approach for patients suffering from nervous system trauma and disease. PMID:25879847

Curcumin analog 1, 5-bis (2-trifluoromethylphenyl)-1, 4-pentadien-3-one exhibits enhanced ability on Nrf2 activation and protection against acrolein-induced ARPE-19 cell toxicity

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Li, Yuan [Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Life Science, FIST, Xi' an Jiaotong University, Xi' an (China); Zou, Xuan [Center for Translational Medicine, FIST, Xi' an Jiaotong University, Xi' an (China); Cao, Ke; Xu, Jie; Yue, Tingting [Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Life Science, FIST, Xi' an Jiaotong University, Xi' an (China); Dai, Fang; Zhou, Bo [State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou (China); Lu, Wuyuan [Center for Translational Medicine, FIST, Xi' an Jiaotong University, Xi' an (China); Feng, Zhihui, E-mail: zhfeng@mail.xjtu.edu.cn [Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Life Science, FIST, Xi' an Jiaotong University, Xi' an (China); Liu, Jiankang, E-mail: j.liu@mail.xjtu.edu.cn [Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Life Science, FIST, Xi' an Jiaotong University, Xi' an (China)

2013-11-01

Curcumin, a phytochemical agent in the spice turmeric, has received increasing attention for its anticancer, anti-inflammatory and antioxidant properties. However, application of curcumin has been limited due to its insolubility in water and poor bioavailability both clinically and experimentally. In addition, the protective effects and mechanisms of curcumin in eye diseases have been poorly studied. In the present study, we synthesized a curcumin analog, 1, 5-bis (2-trifluoromethylphenyl)-1, 4-pentadien-3-one (C3), which displayed improved protective effect against acrolein-induced toxicity in a human retinal pigment epithelial cell line (ARPE-19). At 5 μM, curcumin completely protected against acrolein-induced cell oxidative damage and preserved GSH levels and mitochondrial function. Surprisingly, C3 displayed a complete protective effect at 0.5 μM, which was much more efficient than curcumin. Both 0.5 μM C3 and 5 μM curcumin induced Nrf2 nuclear translocation and Nrf2 target genes transcription similarly. Experiments using Nrf2 siRNA showed that the protective effects of curcumin and C3 were eliminated by Nrf2 knockdown. Additionally, both curcumin and C3 activated the PI3/Akt pathway, however, Nrf2 activation was independent of this pathway, and therefore, we hypothesized that both curcumin and C3 activated phase II enzymes via directly disrupting the Nrf2/Keap1 complex and promoting Nrf2's nuclear translocation. Since acrolein challenge of ARPE-19 cells has been used as a model of smoking and age-related macular degeneration (AMD), we concluded that the curcumin analog, C3, may be a more promising drug candidate for its potential application for the prevention and treatment of eye diseases, such as AMD. - Highlights: • We examine toxicity effects of cigarette smoking component acrolein in retina cells. • We report a more efficient curcumin analog (C3) protecting cellular function. • Mitochondrial function and phase II enzyme activation are the

Curcumin analog 1, 5-bis (2-trifluoromethylphenyl)-1, 4-pentadien-3-one exhibits enhanced ability on Nrf2 activation and protection against acrolein-induced ARPE-19 cell toxicity

International Nuclear Information System (INIS)

Li, Yuan; Zou, Xuan; Cao, Ke; Xu, Jie; Yue, Tingting; Dai, Fang; Zhou, Bo; Lu, Wuyuan; Feng, Zhihui; Liu, Jiankang

2013-01-01

Curcumin, a phytochemical agent in the spice turmeric, has received increasing attention for its anticancer, anti-inflammatory and antioxidant properties. However, application of curcumin has been limited due to its insolubility in water and poor bioavailability both clinically and experimentally. In addition, the protective effects and mechanisms of curcumin in eye diseases have been poorly studied. In the present study, we synthesized a curcumin analog, 1, 5-bis (2-trifluoromethylphenyl)-1, 4-pentadien-3-one (C3), which displayed improved protective effect against acrolein-induced toxicity in a human retinal pigment epithelial cell line (ARPE-19). At 5 μM, curcumin completely protected against acrolein-induced cell oxidative damage and preserved GSH levels and mitochondrial function. Surprisingly, C3 displayed a complete protective effect at 0.5 μM, which was much more efficient than curcumin. Both 0.5 μM C3 and 5 μM curcumin induced Nrf2 nuclear translocation and Nrf2 target genes transcription similarly. Experiments using Nrf2 siRNA showed that the protective effects of curcumin and C3 were eliminated by Nrf2 knockdown. Additionally, both curcumin and C3 activated the PI3/Akt pathway, however, Nrf2 activation was independent of this pathway, and therefore, we hypothesized that both curcumin and C3 activated phase II enzymes via directly disrupting the Nrf2/Keap1 complex and promoting Nrf2's nuclear translocation. Since acrolein challenge of ARPE-19 cells has been used as a model of smoking and age-related macular degeneration (AMD), we concluded that the curcumin analog, C3, may be a more promising drug candidate for its potential application for the prevention and treatment of eye diseases, such as AMD. - Highlights: • We examine toxicity effects of cigarette smoking component acrolein in retina cells. • We report a more efficient curcumin analog (C3) protecting cellular function. • Mitochondrial function and phase II enzyme activation are the major

Mediating the potent ROS toxicity of acrolein in neurons with silica nanoparticles and a natural product approach

Science.gov (United States)

White-Schenk, Désirée.; Shi, Riyi; Leary, James F.

2014-03-01

Acrolein, a very reactive aldehyde, is a culprit in the biochemical cascade after primary, mechanical spinal cord injury (SCI), which leads to the destruction of tissue initially unharmed, referred to as "secondary injury". Additionally, in models of multiple sclerosis (MS) and some clinical research, acrolein levels are significantly increased. Due to its ability to make more copies of itself in the presence of tissue via lipid peroxidation, researchers believe that acrolein plays a role in the increased destruction of the central nervous system in both SCI and MS. Hydralazine, an FDAapproved hypotensive drug, has been shown to scavenge acrolein, but its side effects and short half life at the appropriate dose for acrolein scavenging must be improved for beneficial clinical translation. Therefore, a nanomedical approach has been designed using silica nanoparticles as a porous delivery vehicle hydralazine. The silica particles are formed in a one-step method that incorporates poly(ethylene) glycol (PEG), a stealth molecule, directly onto the nanoparticles. As an additional avenue for study, a natural product in green tea, epigallocatechin gallate (EGCG), has been explored for its ability to react with acrolein, disabling its reactive capabilities. Upon demonstration of attenuating acrolein, EGCG's delivery may also be improved using the nanomedical approach. The current work exposes the potential of using silica nanoparticles as a delivery vehicle and EGCG's antioxidant capabilities in B35 neuroblastoma cells exposed to acrolein. We also measure nanotoxicity to individual rat neurons using high-throughput image scanning cytometry.

Acrolein in wine: importance of 3-hydroxypropionaldehyde and derivatives in production and detection.

Science.gov (United States)

Bauer, Rolene; Cowan, Donald A; Crouch, Andrew

2010-03-24

Certain lactic acid bacteria strains belonging to the genus Lactobacillus have been implicated in the accumulation of 3-hydroxypropionaldehyde (3-HPA) during anaerobic glycerol fermentation. In aqueous solution 3-HPA undergoes reversible dimerization and hydration, resulting in an equilibrium state between different derivatives. Wine quality may be compromised by the presence of 3-HPA due to the potential for spontaneous conversion into acrolein under winemaking conditions. Acrolein is highly toxic and has been implicated in the development of bitterness in wine. Interconversion between 3-HPA derivatives and acrolein is a complex and highly dynamic process driven by hydration and dehydration reactions. Acrolein is furthermore highly reactive and its steady-state concentration in complex systems very low. As a result, analytical detection and quantification in solution is problematic. This paper reviews the biochemical and environmental conditions leading to accumulation of its precursor, 3-HPA. Recent advances in analytical detection are summarized, and the roles played by natural chemical derivatives are highlighted.

Protective Effects of Olive Leaf Extract on Acrolein-Exacerbated Myocardial Infarction via an Endoplasmic Reticulum Stress Pathway

Directory of Open Access Journals (Sweden)

Yuyu Xu

2018-02-01

Full Text Available Many studies reported that air pollution particulate matter (PM exposure was associated with myocardial infarction (MI. Acrolein representing the unsaturated aldehydes, the main component of PM, derives from the incomplete combustion of wood, plastic, fossil fuels and the main constitute of cigarette smoking. However, the effect of acrolein on MI remains not that clear. In the current study, the effect of acrolein-exacerbated MI was investigated. In vivo, male Sprague–Dawley rats received olive leaf extract (OLE followed by acrolein, then isoprenaline (ISO was received by subcutaneous injection to induce MI. Results showed that the expression levels of GRP78 and CHOP, two major components of endoplasmic reticulum (ER stress were higher in the combination of acrolein and ISO than those in ISO treatment. The apoptosis marker, Bax, was also higher while the anti-apoptosis indicator, Bcl2 expression was lower both at protein and mRNA levels in the combination group. Also, the acrolein-protein adducts and myocardial pathological damage increased in the combination of acrolein and ISO relative to the ISO treatment. Besides, cardiac parameters, ejection fraction (EF and fractional shortening (FS were reduced more significantly when acrolein was added than in ISO treatment. Interestingly, all the changes were able to be ameliorated by OLE. Since hydroxytyrosol (HT and oleuropein (OP were the main components in OLE, we next investigated the effect of HT and OP on cardiomyocyte H9c2 cell apoptosis induced by acrolein through ER stress and Bax pathway. Results showed that GRP78, CHOP and Bax expression were upregulated, while Bcl2 expression was downregulated both at the protein and mRNA levels, when the H9c2 cells were treated with acrolein. In addition, pretreatment with HT can reverse the expression of GRP78, CHOP, Bax and Bcl2 on the protein and mRNA levels, while there was no effect of OP on the expression of GRP78 and CHOP on the mRNA levels

Acrolein Exposure in U.S. Tobacco Smokers and Non-Tobacco Users: NHANES 2005-2006.

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Alwis, K Udeni; deCastro, B Rey; Morrow, John C; Blount, Benjamin C

2015-12-01

Acrolein is a highly reactive α,β unsaturated aldehyde and respiratory irritant. Acrolein is formed during combustion (e.g., burning tobacco or biomass), during high-temperature cooking of foods, and in vivo as a product of oxidative stress and polyamine metabolism. No biomonitoring reference data have been reported to characterize acrolein exposure for the U.S. Our goals were to a) evaluate two acrolein metabolites in urine--N-acetyl-S-(3-hydroxypropyl)-L-cysteine (3HPMA) and N-acetyl-S-(2-carboxyethyl)-L-cysteine (CEMA)--as biomarkers of exposure to acrolein for the U.S. population by age, sex, race, and smoking status; and b) assess tobacco smoke as a predictor of acrolein exposure. We analyzed urine from National Health and Nutrition Examination Survey (NHANES 2005-2006) participants ≥ 12 years old (n = 2,866) for 3HPMA and CEMA using ultra-high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UPLC/ESI-MSMS). Sample-weighted linear regression models stratified for non-tobacco users versus tobacco smokers (as defined by serum cotinine and self-report) characterized the association of urinary 3HPMA and CEMA with tobacco smoke exposure, adjusting for urinary creatinine, sex, age, and race/ethnicity. 3HPMA and CEMA levels were higher among tobacco smokers (cigarettes, cigars, and pipe users) than among non-tobacco users. The median 3HPMA levels for tobacco smokers and non-tobacco users were 1,089 and 219 μg/g creatinine, respectively. Similarly, median CEMA levels were 203 μg/g creatinine for tobacco smokers and 78.8 μg/g creatinine for non-tobacco users. Regression analysis showed that serum cotinine was a significant positive predictor (p acrolein exposure in the U.S. population.

Toxic acrolein production due to Ca(2+) influx by the NMDA receptor during stroke.

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Nakamura, Mizuho; Uemura, Takeshi; Saiki, Ryotaro; Sakamoto, Akihiko; Park, Hyerim; Nishimura, Kazuhiro; Terui, Yusuke; Toida, Toshihiko; Kashiwagi, Keiko; Igarashi, Kazuei

2016-01-01

N-Methyl-d-aspartate (NMDA) receptors have a high permeability to Ca(2+), contributing to neuronal cell death after stroke. We recently found that acrolein produced from polyamines is a major toxic compound during stroke. Thus, it was determined whether over-accumulation of Ca(2+) increases the production of acrolein from polyamines in a photochemically-induced thrombosis mouse model of stroke and in cell culture systems. A unilateral infarction was induced in mouse brain by photoinduction after injection of Rose Bengal. The volume of the infarction was analyzed using the public domain National Institutes of Health image program. Protein-conjugated acrolein levels at the locus of infarction and in cells were measured by Western blotting. Levels of polyamines were measured by high-performance liquid chromatography. When the size of brain infarction was decreased by N(1), N(4), N(8)-tribenzylspermidine, a channel blocker of the NMDA receptors, levels of Ca(2+) and protein-conjugated acrolein (PC-Acro) were reduced, while levels of polyamines were increased at the locus of infarction. When cell growth of mouse mammary carcinoma FM3A cells and neuroblastoma Neuro2a cells was inhibited by Ca(2+), the level of polyamines decreased, while that of PC-Acro increased. It was also shown that Ca(2+) toxicity was decreased in an acrolein toxicity decreasing FM3A mutant cells recently isolated. In addition, 20-40 μM Ca(2+) caused the release of polyamines from ribosomes. The results indicate that acrolein is produced from polyamines released from ribosomes through Ca(2+) increase. The results indicate that toxicity of Ca(2+) during brain infarction is correlated with the increase of acrolein. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

[Changes of the Expression of Brain Derived Neurotrophic Factors in Rats Trachea Induced by Acrolein Exposure].

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Yuan, Bing; Yang, Rui-an; Zhao, Wei; Xu, Yan-yan; Dan, Qi-qin; Zhang, Yun-hui

2015-07-01

To investigate expressional changes of brain derived neurotrophic factor (BDNF) in the trachea of rats with acrolein inhalation. Twenty two SD rats were divided into 2 groups: the rats in experimental group were subjected to acrolein inhalation for the induce of trachea inflammatory injury, while the rats with saline (NS) inhalation were as control. All the rats were sacrificed in 1,3,6 weeks after acrolein (n = 11 at each time point) or saline inhalation (n = 11 at each time point), the samples of trachea epithelium were harvested. The immunohistochemistry and in situ hybridization was performed to detect the location of BDNF protein and mRNA in trachea. The expression of BDNF mRNA in the trachea tissues were determined by RT-PCR. There are positive cells in epithelium of trachea for BDNF protein and mRNA, with cytoplasm staining. The expression of BDNF mRNA in the trachea was increased at 1 week after acrolein inhalation (P 0.05). The inflammatory injury in trachea induced by acrolein exposure could be associated with the increased expression of BDNF. BDNF may be one of the crucial inflammatory factors in the process of inflammatory reaction in trachea with acrolein stimulation.

Enhancement of the acrolein-induced production of reactive oxygen species and lung injury by GADD34.

Science.gov (United States)

Sun, Yang; Ito, Sachiko; Nishio, Naomi; Tanaka, Yuriko; Chen, Nana; Liu, Lintao; Isobe, Ken-ichi

2015-01-01

Chronic obstructive pulmonary disease (COPD) is characterized by lung destruction and inflammation. As a major compound of cigarette smoke, acrolein plays a critical role in the induction of respiratory diseases. GADD34 is known as a growth arrest and DNA damage-related gene, which can be overexpressed in adverse environmental conditions. Here we investigated the effects of GADD34 on acrolein-induced lung injury. The intranasal exposure of acrolein induced the expression of GADD34, developing the pulmonary damage with inflammation and increase of reactive oxygen species (ROS). Conversely, the integrality of pulmonary structure was preserved and the generation of ROS was reduced in GADD34-knockout mice. Acrolein-induced phosphorylation of eIF2α in GADD34-knockout epithelial cells by shRNA protected cell death by reducing misfolded protein-caused oxidative stress. These data indicate that GADD34 participates in the development of acrolein-induced lung injury.

Acrolein Is a Pathogenic Mediator of Alcoholic Liver Disease and the Scavenger Hydralazine Is Protective in MiceSummary

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Wei-Yang Chen

2016-09-01

Full Text Available Background & Aims: Alcoholic liver disease (ALD remains a major cause of morbidity and mortality, with no Food and Drug Administration–approved therapy. Chronic alcohol consumption causes a pro-oxidant environment and increases hepatic lipid peroxidation, with acrolein being the most reactive/toxic by-product. This study investigated the pathogenic role of acrolein in hepatic endoplasmic reticulum (ER stress, steatosis, and injury in experimental ALD, and tested acrolein elimination/scavenging (using hydralazine as a potential therapy in ALD. Methods: In vitro (rat hepatoma H4IIEC cells and in vivo (chronic+binge alcohol feeding in C57Bl/6 mice models were used to examine alcohol-induced acrolein accumulation and consequent hepatic ER stress, apoptosis, and injury. In addition, the potential protective effects of the acrolein scavenger, hydralazine, were examined both in vitro and in vivo. Results: Alcohol consumption/metabolism resulted in hepatic accumulation of acrolein-protein adducts, by up-regulation of cytochrome P4502E1 and alcohol dehydrogenase, and down-regulation of glutathione-s-transferase-P, which metabolizes/detoxifies acrolein. Alcohol-induced acrolein adduct accumulation led to hepatic ER stress, proapoptotic signaling, steatosis, apoptosis, and liver injury; however, ER-protective/adaptive responses were not induced. Notably, direct exposure to acrolein in vitro mimicked the in vivo effects of alcohol, indicating that acrolein mediates the adverse effects of alcohol. Importantly, hydralazine, a known acrolein scavenger, protected against alcohol-induced ER stress and liver injury, both in vitro and in mice. Conclusions: Our study shows the following: (1 alcohol consumption triggers pathologic ER stress without ER adaptation/protection; (2 alcohol-induced acrolein is a potential therapeutic target and pathogenic mediator of hepatic ER stress, cell death, and injury; and (3 removal/clearance of acrolein

SPATIAL AND TEMPORAL VARIABILITY IN ACROLEIN AND SELECT VOLATILE ORGANIC COMPOUNDS IN DETROIT, MICHIGAN

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The variability in outdoor concentrations of acrolein, benzene, toluene, ethylbenzene and xylenes (BTEX), and 1,3-butadiene was examined for data measured during summer 2004 of the Detroit Exposure and Aerosol Research Study (DEARS). Results for acrolein indicated no significant...

Airborne acrolein induces keratin-8 (Ser-73) hyperphosphorylation and intermediate filament ubiquitination in bronchiolar lung cell monolayers.

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Burcham, Philip C; Raso, Albert; Henry, Peter J

2014-05-07

The combustion product acrolein is a key mediator of pulmonary edema in victims of smoke inhalation injury. Since studying acrolein toxicity in conventional in vitro systems is complicated by reactivity with nucleophilic culture media constituents, we explored an exposure system which delivers airborne acrolein directly to lung cell monolayers at the air-liquid interface. Calu-3 lung adenocarcinoma cells were maintained on membrane inserts such that the basal surface was bathed in nucleophile-free media while the upper surface remained in contact with acrolein-containing air. Cells were exposed to airborne acrolein for 30 min before they were allowed to recover in fresh media, with cell sampling at defined time points to allow evaluation of toxicity and protein damage. After prior exposure to acrolein, cell ATP levels remained close to controls for 4h but decreased in an exposure-dependent manner by 24h. A loss of transepithelial electrical resistance and increased permeability to fluorescein isothiocyanate-labeled dextran preceded ATP loss. Use of antibody arrays to monitor protein expression in exposed monolayers identified strong upregulation of phospho-keratin-8 (Ser(73)) as an early consequence of acrolein exposure. These changes were accompanied by chemical damage to keratin-8 and other intermediate filament family members, while acrolein exposure also resulted in controlled ubiquitination of high mass proteins within the intermediate filament extracts. These findings confirm the usefulness of systems allowing delivery of airborne smoke constituents to lung cell monolayers during studies of the molecular basis for acute smoke intoxication injury. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Effect of sildenafil on acrolein-induced airway inflammation and mucus production in rats.

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Wang, T; Liu, Y; Chen, L; Wang, X; Hu, X-R; Feng, Y-L; Liu, D-S; Xu, D; Duan, Y-P; Lin, J; Ou, X-M; Wen, F-Q

2009-05-01

Airway inflammation with mucus overproduction is a distinguishing pathophysiological feature of many chronic respiratory diseases. Phosphodiesterase (PDE) inhibitors have shown anti-inflammatory properties. In the present study, the effect of sildenafil, a potent inhibitor of PDE5 that selectively degrades cyclic guanosine 3',5'-monophosphate (cGMP), on acrolein-induced inflammation and mucus production in rat airways was examined. Rats were exposed to acrolein for 14 and 28 days. Sildenafil or distilled saline was administered intragastrically prior to acrolein exposure. Bronchoalveolar lavage fluid (BALF) was acquired for cell count and the detection of pro-inflammatory cytokine levels. Lung tissue was examined for cGMP content, nitric oxide (NO)-metabolite levels, histopathological lesion scores, goblet cell metaplasia and mucin production. The results suggested that sildenafil pretreatment reversed the significant decline of cGMP content in rat lungs induced by acrolein exposure, and suppressed the increase of lung NO metabolites, the BALF leukocyte influx and pro-inflammatory cytokine release. Moreover, sildenafil pretreatment reduced acrolein-induced Muc5ac mucin synthesis at both mRNA and protein levels, and attenuated airway inflammation, as well as epithelial hyperplasia and metaplasia. In conclusion, sildenafil could attenuate airway inflammation and mucus production in the rat model, possibly through the nitric oxide/cyclic guanosine 3',5'-monophosphate pathway, and, thus, might have a therapeutic potential for chronic airway diseases.

Enhancement of the Acrolein-Induced Production of Reactive Oxygen Species and Lung Injury by GADD34

Science.gov (United States)

Sun, Yang; Ito, Sachiko; Nishio, Naomi; Tanaka, Yuriko; Chen, Nana; Isobe, Ken-ichi

2015-01-01

Chronic obstructive pulmonary disease (COPD) is characterized by lung destruction and inflammation. As a major compound of cigarette smoke, acrolein plays a critical role in the induction of respiratory diseases. GADD34 is known as a growth arrest and DNA damage-related gene, which can be overexpressed in adverse environmental conditions. Here we investigated the effects of GADD34 on acrolein-induced lung injury. The intranasal exposure of acrolein induced the expression of GADD34, developing the pulmonary damage with inflammation and increase of reactive oxygen species (ROS). Conversely, the integrality of pulmonary structure was preserved and the generation of ROS was reduced in GADD34-knockout mice. Acrolein-induced phosphorylation of eIF2α in GADD34-knockout epithelial cells by shRNA protected cell death by reducing misfolded protein-caused oxidative stress. These data indicate that GADD34 participates in the development of acrolein-induced lung injury. PMID:25821552

Enhancement of the Acrolein-Induced Production of Reactive Oxygen Species and Lung Injury by GADD34

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Yang Sun

2015-01-01

Full Text Available Chronic obstructive pulmonary disease (COPD is characterized by lung destruction and inflammation. As a major compound of cigarette smoke, acrolein plays a critical role in the induction of respiratory diseases. GADD34 is known as a growth arrest and DNA damage-related gene, which can be overexpressed in adverse environmental conditions. Here we investigated the effects of GADD34 on acrolein-induced lung injury. The intranasal exposure of acrolein induced the expression of GADD34, developing the pulmonary damage with inflammation and increase of reactive oxygen species (ROS. Conversely, the integrality of pulmonary structure was preserved and the generation of ROS was reduced in GADD34-knockout mice. Acrolein-induced phosphorylation of eIF2α in GADD34-knockout epithelial cells by shRNA protected cell death by reducing misfolded protein-caused oxidative stress. These data indicate that GADD34 participates in the development of acrolein-induced lung injury.

Acrolein enhances epigenetic modifications, FasL expression and hepatocyte toxicity induced by anti-HIV drug Zidovudine.

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Ghare, Smita S; Donde, Hridgandh; Chen, Wei-Yang; Barker, David F; Gobejishvilli, Leila; McClain, Craig J; Barve, Shirish S; Joshi-Barve, Swati

2016-09-01

Zidovudine (AZT) remains the mainstay of antiretroviral therapy against HIV in resource-poor countries; however, its use is frequently associated with hepatotoxicity. Not all HIV patients on AZT develop hepatotoxicity, and the determining factors are unclear. Alcohol consumption and cigarette smoking are known risk factors for HIV hepatotoxicity, and both are significant sources of acrolein, a highly reactive and toxic aldehyde. This study examines the potential hepatotoxic interactions between acrolein and AZT. Our data demonstrate that acrolein markedly enhanced AZT-induced transcriptionally permissive histone modifications (H3K9Ac and H3K9Me3) allowing the recruitment of transcription factor NF-kB and RNA polymerase II at the FasL gene promoter, resulting in FasL upregulation and apoptosis in hepatocytes. Notably, the acrolein scavenger, hydralazine prevented these promoter-associated epigenetic changes and inhibited FasL upregulation and apoptosis induced by the combination of AZT and acrolein, as well as AZT alone. Our data strongly suggest that acrolein enhancement of promoter histone modifications and FasL upregulation are major pathogenic mechanisms driving AZT-induced hepatotoxicity. Moreover, these data also indicate the therapeutic potential of hydralazine in mitigating AZT hepatotoxicity. Copyright © 2016 Elsevier B.V. All rights reserved.

Mechanisms of CDDO-imidazolide-mediated cytoprotection against acrolein-induced neurocytotoxicity in SH-SY5Y cells and primary human astrocytes.

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Speen, Adam; Jones, Colton; Patel, Ruby; Shah, Halley; Nallasamy, Palanisamy; Brooke, Elizabeth A S; Zhu, Hong; Li, Y Robert; Jia, Zhenquan

2015-10-01

Acrolein is a ubiquitous unsaturated aldehyde has been implicated in the pathogenesis of various neurological disorders. However, limited study has been conducted into potential therapeutic protection and underlying mechanism against acrolein-induced cytotoxicity via upregulation of cellular aldehyde-detoxification defenses. In this study we have utilized RA-differentiated human SH-SY5Y cells and primary human astrocytes to investigate the induction of glutathione (GSH) by the synthetic triterpenoid 2-cyano-3,12-dixooleana-1,9-dien-28-imidazolide (CDDO-Im) and the protective effects CDDO-Im-mediated antioxidant defenses on acrolein toxicity. Acrolein exposure to RA-differentiated SH-SY5Y cells resulted in a significant time dependent depletion of cellular GSH preceding a reduction in cell viability and LDH release. Further, we demonstrated the predominance of cellular GSH in protection against acrolein-induced cytotoxicity. Buthionine sulfoximine (BSO) at 25μM dramatically depleted GSH and significantly potentiated acrolein-induced cytotoxicity. Pretreatment of the cells with 100nM CDDO-Im afforded a dramatic protection against acrolein-induced cytotoxicity. Pretreatment of BSO and CDDO was found to prevent the CDDO-Im-mediated GSH induction and partially reversed the cytoprotective effects of CDDO-Im against acrolein cytotoxicity. Overall, this study represents for the first time the CDDO-Im mediated upregulation of GSH is a predominant mechanism against acrolein-induced neurotoxicity. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Isotope-labeling studies on the formation pathway of acrolein during heat processing of oils.

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Ewert, Alice; Granvogl, Michael; Schieberle, Peter

2014-08-20

Acrolein (2-propenal) is classified as a foodborne toxicant and was shown to be present in significant amounts in heated edible oils. Up to now, its formation was mainly suggested to be from the glycerol part of triacylglycerides, although a clear influence of the unsaturation of the fatty acid moiety was also obvious in previous studies. To unequivocally clarify the role of the glycerol and the fatty acid parts in acrolein formation, two series of labeled triacylglycerides were synthesized: [(13)C(3)]-triacylglycerides of stearic, oleic, linoleic, and linolenic acid and [(13)C(54)]-triacylglycerides with labeled stearic, oleic, and linoleic acid, but with unlabeled glycerol. Heating of each of the seven intermediates singly in silicon oil and measurement of the formed amounts of labeled and unlabeled acrolein clearly proved the fatty acid backbone as the key precursor structure. Enzymatically synthesized pure linoleic acid and linolenic acid hydroperoxides were shown to be the key intermediates in acrolein formation, thus allowing the discussion of a radical-induced reaction pathway leading to the formation of the aldehyde. Surprisingly, although several oils contained high amounts of acrolein after heating, deep-fried foods themselves, such as donuts or French fries, were low in the aldehyde.

Crude glycerol combustion: Particulate, acrolein, and other volatile organic emissions

KAUST Repository

Steinmetz, Scott

2013-01-01

Crude glycerol is an abundant by-product of biodiesel production. As volumes of this potential waste grow, there is increasing interest in developing new value added uses. One possible use, as a boiler fuel for process heating, offers added advantages of energy integration and fossil fuel substitution. However, challenges to the use of crude glycerol as a boiler fuel include its low energy density, high viscosity, and high autoignition temperature. We have previously shown that a refractory-lined, high swirl burner can overcome challenges related to flame ignition and stability. However, critical issues related to ash behavior and the possible formation of acrolein remained. The work presented here indicates that the presence of dissolved catalysts used during the esterification and transesterification processes results in extremely large amounts of inorganic species in the crude glycerol. For the fuels examined here, the result is a submicron fly ash comprised primarily of sodium carbonates, phosphates, and sulfates. These particles report to a well-developed accumulation mode (0.3-0.7 μm diameter), indicating extensive ash vaporization and particle formation via nucleation, condensation, and coagulation. Particle mass emissions were between 2 and 4 g/m3. These results indicate that glycerol containing soluble catalyst is not suitable as a boiler fuel. Fortunately, process improvements are currently addressing this issue. Additionally, acrolein is of concern due to its toxicity, and is known to be formed from the low temperature thermal decomposition of glycerol. Currently, there is no known reliable method for measuring acrolein in sources. Acrolein and emissions of other volatile organic compounds were characterized through the use of a SUMMA canister-based sampling method followed by GC-MS analysis designed for ambient measurements. Results indicate crude glycerol combustion produces relatively small amounts of acrolein (∼15 ppbv) and other volatile organic

Metabolism and binding of cyclophosphamide and its metabolite acrolein to rat hepatic microsomal cytochrome P-450

International Nuclear Information System (INIS)

Marinello, A.J.; Bansal, S.K.; Paul, B.; Koser, P.L.; Love, J.; Struck, R.F.; Gurtoo, H.L.

1984-01-01

The hepatic cytochrome P-450-mediated metabolism and metabolic activation of [chloroethyl-3H]cyclophosphamide [( chloroethyl-3H]CP) and [4-14C]cyclophosphamide [( 4-14C]CP) were investigated in vitro in the reconstituted system containing cytochrome P-450 isolated from phenobarbital-treated rats. In addition, hepatic microsomal binding and the hepatic microsome-mediated metabolism of [14C]acrolein, a metabolite of [4-14C]CP, were also investigated. The metabolism of [chloroethyl-3H]CP and [4-14C]CP to polar metabolites was found to depend on the presence of NADPH and showed concentration dependence with respect to cytochrome P-450 and NADPH:cytochrome P-450 reductase. Km and Vmax values were essentially similar. The patterns of inhibition by microsomal mixed-function oxidase inhibitors, anti-cytochrome P-450 antibody, and heat denaturation of the cytochrome P-450 were essentially similar, with subtle differences between [4-14C]CP and [chloroethyl-3H]CP metabolism. The in vitro metabolic activation of CP in the reconstituted system demonstrated predominant binding of [chloroethyl-3H]CP to nucleic acids and almost exclusive binding of [4-14C]CP to proteins. Gel electrophoresis-fluorography of the proteins in the reconstituted system treated with [4-14C]CP demonstrated localization of the 14C label in the cytochrome P-450 region. To examine this association further, hepatic microsomes were modified with [14C]acrolein in the presence and the absence of NADPH. The results confirmed covalent association between [14C]acrolein and cytochrome P-450 in the microsomes and also demonstrated further metabolism of [14C]acrolein, apparently to an epoxide, which is capable of binding covalently to proteins. The results of these investigations not only confirm the significance of primary metabolism but also emphasize the potential role of the secondary metabolism of cyclophosphamide in some of its toxic manifestations

Acrolein acts as a neurotoxin in the nigrostriatal dopaminergic system of rat: involvement of ?-synuclein aggregation and programmed cell death

OpenAIRE

Wang, Yi-Ting; Lin, Hui-Ching; Zhao, Wei-Zhong; Huang, Hui-Ju; Lo, Yu-Li; Wang, Hsiang-Tsui; Maan-Yuh Lin, Anya

2017-01-01

Clinical studies report significant increases in acrolein (an ?,?-unsaturated aldehyde) in the substantia nigra (SN) of patients with Parkinson?s disease (PD). In the present study, acrolein-induced neurotoxicity in the nigrostriatal dopaminergic system was investigated by local infusion of acrolein (15, 50, 150?nmoles/0.5??l) in the SN of Sprague-Dawley rats. Acrolein-induced neurodegeneration of nigrostriatal dopaminergic system was delineated by reductions in tyrosine hydroxylase (TH) leve...

Enhancement of the Acrolein-Induced Production of Reactive Oxygen Species and Lung Injury by GADD34

OpenAIRE

Sun, Yang; Ito, Sachiko; Nishio, Naomi; Tanaka, Yuriko; Chen, Nana; Liu, Lintao; Isobe, Ken-ichi

2015-01-01

Chronic obstructive pulmonary disease (COPD) is characterized by lung destruction and inflammation. As a major compound of cigarette smoke, acrolein plays a critical role in the induction of respiratory diseases. GADD34 is known as a growth arrest and DNA damage-related gene, which can be overexpressed in adverse environmental conditions. Here we investigated the effects of GADD34 on acrolein-induced lung injury. The intranasal exposure of acrolein induced the expression of GADD34, developing...

Acrolein and asthma attack prevalence in a representative sample of the United States adult population 2000-2009.

Science.gov (United States)

deCastro, B Rey

2014-01-01

Acrolein is an air toxic and highly potent respiratory irritant. There is little epidemiology available, but US EPA estimates that outdoor acrolein is responsible for about 75 percent of non-cancer respiratory health effects attributable to air toxics in the United States, based on the Agency's 2005 NATA (National-Scale Air Toxics Assessment) and acrolein's comparatively potent inhalation reference concentration of 0.02 µg/m3. Assess the association between estimated outdoor acrolein exposure and asthma attack reported by a representative cross-sectional sample of the adult United States population. NATA 2005 chronic outdoor acrolein exposure estimates at the census tract were linked with residences oif adults (≥18 years old) in the NHIS (National Health Interview Survey) 2000-2009 (n = 271,348 subjects). A sample-weighted logistic regression model characterized the association between the prevalence of reporting at least one asthma attack in the 12 months prior to survey interview and quintiles of exposure to outdoor acrolein, controlling for potential confounders. In the highest quintile of outdoor acrolein exposure (0.05-0.46 µg/m3), there was a marginally significant increase in the asthma attack pOR (prevalence-odds ratio [95% CI]  = 1.08 [0.98∶1.19]) relative to the lowest quintile. The highest quintile was also associated with a marginally significant increase in prevalence-odds (1.13 [0.98∶1.29]) in a model limited to never smokers (n = 153,820). Chronic exposure to outdoor acrolein of 0.05-0.46 µg/m3 appears to increase the prevalence-odds of having at least one asthma attack in the previous year by 8 percent in a representative cross-sectional sample of the adult United States population.

Acrolein and asthma attack prevalence in a representative sample of the United States adult population 2000-2009.

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B Rey deCastro

Full Text Available BACKGROUND: Acrolein is an air toxic and highly potent respiratory irritant. There is little epidemiology available, but US EPA estimates that outdoor acrolein is responsible for about 75 percent of non-cancer respiratory health effects attributable to air toxics in the United States, based on the Agency's 2005 NATA (National-Scale Air Toxics Assessment and acrolein's comparatively potent inhalation reference concentration of 0.02 µg/m3. OBJECTIVES: Assess the association between estimated outdoor acrolein exposure and asthma attack reported by a representative cross-sectional sample of the adult United States population. METHODS: NATA 2005 chronic outdoor acrolein exposure estimates at the census tract were linked with residences oif adults (≥18 years old in the NHIS (National Health Interview Survey 2000-2009 (n = 271,348 subjects. A sample-weighted logistic regression model characterized the association between the prevalence of reporting at least one asthma attack in the 12 months prior to survey interview and quintiles of exposure to outdoor acrolein, controlling for potential confounders. RESULTS: In the highest quintile of outdoor acrolein exposure (0.05-0.46 µg/m3, there was a marginally significant increase in the asthma attack pOR (prevalence-odds ratio [95% CI]  = 1.08 [0.98∶1.19] relative to the lowest quintile. The highest quintile was also associated with a marginally significant increase in prevalence-odds (1.13 [0.98∶1.29] in a model limited to never smokers (n = 153,820. CONCLUSIONS: Chronic exposure to outdoor acrolein of 0.05-0.46 µg/m3 appears to increase the prevalence-odds of having at least one asthma attack in the previous year by 8 percent in a representative cross-sectional sample of the adult United States population.

Protection of HepG2 cells against acrolein toxicity by 2-cyano-3,12-dioxooleana-1,9-dien-28-imidazolide via glutathione-mediated mechanism.

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Shah, Halley; Speen, Adam M; Saunders, Christina; Brooke, Elizabeth A S; Nallasamy, Palanisamy; Zhu, Hong; Li, Y Robert; Jia, Zhenquan

2015-10-01

Acrolein is an environmental toxicant, mainly found in smoke released from incomplete combustion of organic matter. Several studies showed that exposure to acrolein can lead to liver damage. The mechanisms involved in acrolein-induced hepatocellular toxicity, however, are not completely understood. This study examined the cytotoxic mechanisms of acrolein on HepG2 cells. Acrolein at pathophysiological concentrations was shown to cause apoptotic cell death and an increase in levels of protein carbonyl and thiobarbituric acid reactive acid substances. Acrolein also rapidly depleted intracellular glutathione (GSH), GSH-linked glutathione-S-transferases, and aldose reductase, three critical cellular defenses that detoxify reactive aldehydes. Results further showed that depletion of cellular GSH by acrolein preceded the loss of cell viability. To further determine the role of cellular GSH in acrolein-mediated cytotoxicity, buthionine sulfoximine (BSO) was used to inhibit cellular GSH biosynthesis. It was observed that depletion of cellular GSH by BSO led to a marked potentiation of acrolein-mediated cytotoxicity in HepG2 cells. To further assess the contribution of these events to acrolein-induced cytotoxicity, triterpenoid compound 2-cyano-3,12-dioxooleana-1,9-dien-28-imidazolide (CDDO-Im) was used for induction of GSH. Induction of GSH by CDDO-Im afforded cytoprotection against acrolein toxicity in HepG2 cells. Furthermore, BSO significantly inhibited CDDO-Im-mediated induction in cellular GSH levels and also reversed cytoprotective effects of CDDO-Im in HepG2 cells. These results suggest that GSH is a predominant mechanism underlying acrolein-induced cytotoxicity as well as CDDO-Im-mediated cytoprotection. This study may provide understanding on the molecular action of acrolein which may be important to develop novel strategies for the prevention of acrolein-mediated toxicity. © 2014 by the Society for Experimental Biology and Medicine.

Determination of acrolein, ethanol, volatile acidity, and copper in different samples of sugarcane spirits

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José Masson

2012-09-01

Full Text Available Seventy-one samples of sugarcane spirits from small and average size stills produced in the northern and southern Minas Gerais (Brazil were analyzed for acrolein using HPLC (High Performance Liquid Chromatography. Ethanol and copper concentrations and volatile acidity were also determined according to methods established by the Ministry of Agriculture, Livestock and Supply (MAPA. A total of 9.85% of the samples tested showed levels of acrolein above the legal limits, while the copper concentrations of 21.00% of the samples and the volatile acidity of 8.85% of the samples were higher than the limits established by the Brazilian legislation. The concentration of acrolein varied from 0 to 21.97 mg.100 mL-1 of ethanol. However, no significant difference at 5% of significance was observed between the samples produced in the northern and southern Minas Gerais. The method used for determination of acrolein in sugarcane spirits involved the formation of a derivative with 2,4-dinitrophenylhydrazine (2,4-DNPH and subsequent analysis by HPLC.

Selective oxidation of propylene to acrolein by hydrothermally synthesized bismuth molybdates

DEFF Research Database (Denmark)

Schuh, Kirsten; Kleist, Wolfgang; Høj, Martin

2014-01-01

Hydrothermal synthesis has been used as a soft chemical method to prepare bismuth molybdate catalysts for the selective oxidation of propylene to acrolein. All obtained samples displayed a plate-like morphology, but their individual aspect ratios varied with the hydrothermal synthesis conditions...... of nitric acid during hydrothermal synthesis enhanced both propylene conversion and acrolein yield, possibly due to a change in morphology. Formation of β-Bi2Mo2O9 was not observed under the applied conditions. In general, the catalytic performance of all samples decreased notably after calcination at 550...

Anthocyanins Protect SK-N-SH Cells Against Acrolein-Induced Toxicity by Preserving the Cellular Redox State.

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Belkacemi, Abdenour; Ramassamy, Charles

2016-01-01

In Alzheimer's disease (AD) and in mild cognitive impairment (MCI) patients, by-products of lipid peroxidation such as acrolein accumulated in vulnerable regions of the brain. We have previously shown that acrolein is a highly reactive and neurotoxic aldehyde and its toxicity involves the alteration of several redox-sensitive pathways. Recently, protein-conjugated acrolein in cerebrospinal fluid has been proposed as a biomarker to distinguish between MCI and AD. With growing evidence of the early involvement of oxidative stress in AD etiology, one would expect that a successful therapy should prevent brain oxidative damage. In this regard, several studies have demonstrated that polyphenol-rich extracts exert beneficial effect on cognitive impairment and oxidative stress. We have recently demonstrated the efficacy of an anthocyanin formulation (MAF14001) against amyloid-β-induced oxidative stress. The aim of this study is to investigate the neuroprotective effect of MAF14001 as a mixture of anthocyanins, a particular class of polyphenols, against acrolein-induced oxidative damage in SK-N-SH neuronal cells. Our results demonstrated that MAF14001, from 5μM, was able to efficiently protect SK-N-SH cells against acrolein-induced cell death. MAF14001 was able to lower reactive oxygen species and protein carbonyl levels induced by acrolein. Moreover, MAF1401 prevented glutathione depletion and positively modulated, in the presence of acrolein, some oxidative stress-sensitive pathways including the transcription factors NF-κB and Nrf2, the proteins γ-GCS and GSK3β, and the protein adaptator p66Shc. Along with its proven protective effect against amyloid-β toxicity, these results demonstrate that MAF14001 could target multiple mechanisms and could be a promising agent for AD prevention.

Acrolein increases macrophage atherogenicity in association with gut microbiota remodeling in atherosclerotic mice: protective role for the polyphenol-rich pomegranate juice.

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Rom, Oren; Korach-Rechtman, Hila; Hayek, Tony; Danin-Poleg, Yael; Bar, Haim; Kashi, Yechezkel; Aviram, Michael

2017-04-01

The unsaturated aldehyde acrolein is pro-atherogenic, and the polyphenol-rich pomegranate juice (PJ), known for its anti-oxidative/anti-atherogenic properties, inhibits macrophage foam cell formation, the hallmark feature of early atherosclerosis. This study aimed to investigate two unexplored areas of acrolein atherogenicity: macrophage lipid metabolism and the gut microbiota composition. The protective effects of PJ against acrolein atherogenicity were also evaluated. Atherosclerotic apolipoprotein E-deficient (apoE -/- ) mice that were fed acrolein (3 mg/kg/day) for 1 month showed significant increases in serum and aortic cholesterol, triglycerides, and lipid peroxides. In peritoneal macrophages isolated from the mice and in J774A.1 cultured macrophages, acrolein exposure increased intracellular oxidative stress and stimulated cholesterol and triglyceride accumulation via enhanced rates of their biosynthesis and over-expression of key regulators of cellular lipid biosynthesis: sterol regulatory element-binding proteins (SREBPs), 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR), and diacylglycerol acyltransferase1 (DGAT1). Acrolein-fed mice demonstrated a major shift in the gut microbiota composition, including a significant phylum-level change in increased Firmicutes and decreased Bacteroidetes. At the family level, acrolein significantly increased the prevalence of Ruminococcaceae and Lachnospiraceae of which the Coprococcus genus was significantly and positively correlated with serum, aortic and macrophage lipid levels and peroxidation. The pro-atherogenic effects of acrolein on serum, aortas, macrophages, and the gut microbiota were substantially abolished by PJ. In conclusion, these findings provide novel mechanisms by which acrolein increases macrophage lipid accumulation and alters the gut microbiota composition in association with enhanced atherogenesis. Moreover, PJ was found as an effective strategy against acrolein atherogenicity.

A tailored catalyst for the sustainable conversion of glycerol to acrolein: mechanistic aspect of sequential dehydration.

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Yun, Danim; Kim, Tae Yong; Park, Dae Sung; Yun, Yang Sik; Han, Jeong Woo; Yi, Jongheop

2014-08-01

Developing a catalyst to resolve deactivation caused from coke is a primary challenge in the dehydration of glycerol to acrolein. An open-macropore-structured and Brønsted-acidic catalyst (Marigold-like silica functionalized with sulfonic acid groups, MS-FS) was synthesized for the stable and selective production of acrolein from glycerol. A high acrolein yield of 73% was achieved and maintained for 50 h in the presence of the MS-FS catalyst. The hierarchical structure of the catalyst with macropores was found to have an important effect on the stability of the catalyst because coke polymerization and pore blocking caused by coke deposition were inhibited. In addition, the behavior of 3-hydroxypropionaldehyde (3-HPA) during the sequential dehydration was studied using density functional theory (DFT) calculations because 3-HPA conversion is one of the main causes for coke formation. We found that the easily reproducible Brønsted acid sites in MS-FS permit the selective and stable production of acrolein. This is because the reactive intermediate (3-HPA) is readily adsorbed on the regenerated acid sites, which is essential for the selective production of acrolein during the sequential dehydration. The regeneration ability of the acid sites is related not only to the selective production of acrolein but also to the retardation of catalyst deactivation by suppressing the formation of coke precursors originating from 3-HPA degradation. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chlamydomonas reinhardtii responding to high light: a role for 2-propenal (acrolein).

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Roach, Thomas; Baur, Theresa; Stöggl, Wolfgang; Krieger-Liszkay, Anja

2017-09-01

High light causes photosystem II to generate singlet oxygen ( 1 O 2 ), a reactive oxygen species (ROS) that can react with membrane lipids, releasing reactive electrophile species (RES), such as acrolein. To investigate how RES may contribute to light stress responses, Chlamydomonas reinhardtii was high light-treated in photoautotrophic and mixotrophic conditions and also in an oxygen-enriched atmosphere to elevate ROS production. The responses were compared to exogenous acrolein. Non-photochemical quenching (NPQ) was higher in photoautotrophic cells, as a consequence of a more de-epoxidized state of the xanthophyll cycle pool and more LHCSR3 protein, showing that photosynthesis was under more pressure than in mixotrophic cells. Photoautotrophic cells had lowered α-tocopherol and β-carotene contents and a higher level of protein carbonylation, indicators of elevated 1 O 2 production. Levels of glutathione, glutathione peroxidase (GPX5) and glutathione-S-transferase (GST1), important antioxidants against RES, were also increased in photoautotrophic cells. In parallel to the wild-type, the LHCSR3-deficient npq4 mutant was high light-treated, which in photoautotrophic conditions exhibited particular sensitivity under elevated oxygen, the treatment that induced the highest RES levels, including acrolein. The npq4 mutant had more GPX5 and GST1 alongside higher levels of carbonylated protein and a more oxidized glutathione redox state. In wild-type cells glutathione contents doubled after 4 h treatment, either with high light under elevated oxygen or with a non-critical dose (600 ppm) of acrolein. Exogenous acrolein also increased GST1 levels, but not GPX5. Overall, RES-associated oxidative damage and glutathione metabolism are prominently associated with light stress and potentially in signaling responses of C. reinhardtii. © 2017 Scandinavian Plant Physiology Society.

Acrolein and Asthma Attack Prevalence in a Representative Sample of the United States Adult Population 2000 – 2009

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deCastro, B. Rey

2014-01-01

Background Acrolein is an air toxic and highly potent respiratory irritant. There is little epidemiology available, but US EPA estimates that outdoor acrolein is responsible for about 75 percent of non-cancer respiratory health effects attributable to air toxics in the United States, based on the Agency's 2005 NATA (National-Scale Air Toxics Assessment) and acrolein's comparatively potent inhalation reference concentration of 0.02 µg/m3. Objectives Assess the association between estimated outdoor acrolein exposure and asthma attack reported by a representative cross-sectional sample of the adult United States population. Methods NATA 2005 chronic outdoor acrolein exposure estimates at the census tract were linked with residences oif adults (≥18 years old) in the NHIS (National Health Interview Survey) 2000 – 2009 (n = 271,348 subjects). A sample-weighted logistic regression model characterized the association between the prevalence of reporting at least one asthma attack in the 12 months prior to survey interview and quintiles of exposure to outdoor acrolein, controlling for potential confounders. Results In the highest quintile of outdoor acrolein exposure (0.05 – 0.46 µg/m3), there was a marginally significant increase in the asthma attack pOR (prevalence-odds ratio [95% CI]  = 1.08 [0.98∶1.19]) relative to the lowest quintile. The highest quintile was also associated with a marginally significant increase in prevalence-odds (1.13 [0.98∶1.29]) in a model limited to never smokers (n = 153,820). Conclusions Chronic exposure to outdoor acrolein of 0.05 – 0.46 µg/m3 appears to increase the prevalence-odds of having at least one asthma attack in the previous year by 8 percent in a representative cross-sectional sample of the adult United States population. PMID:24816802

Idh2 Deficiency Exacerbates Acrolein-Induced Lung Injury through Mitochondrial Redox Environment Deterioration

OpenAIRE

Park, Jung Hyun; Ku, Hyeong Jun; Lee, Jin Hyup; Park, Jeen-Woo

2017-01-01

Acrolein is known to be involved in acute lung injury and other pulmonary diseases. A number of studies have suggested that acrolein-induced toxic effects are associated with depletion of antioxidants, such as reduced glutathione and protein thiols, and production of reactive oxygen species. Mitochondrial NADP+-dependent isocitrate dehydrogenase (idh2) regulates mitochondrial redox balance and reduces oxidative stress-induced cell injury via generation of NADPH. Therefore, we evaluated the ro...

The Reactions of Nitrogen Heterocycles with Acrolein: Scope and Prebiotic Significance

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Cleaves, H. James

2002-12-01

It has been suggested that life began with a self-replicating RNA molecule. However, after much research into the prebiotic synthesis of RNA, the difficulties encountered have lead some to hypothesize that RNA was preceded by a simpler molecule, one more easily synthesized prebiotically. Many of the proposed alternative molecules are based on acrolein, since it reacts readily with nucleophiles, such as the nucleobases, via Michael addition and is readily synthesized from formaldehyde and acetaldehyde. Reports regarding the reactions of nucleobases with concentrated acrolein solutions suggest that this is a plausible reaction mechanism, though there are also reports that the "incorrect" isomers are obtained. The scope and kinetics of the reaction of acrolein with various nitrogen heterocycles are reported here. Reactions of pyrimidines often give N1 adducts as the major products. Reactions of purines often give N9 adducts in good yield. The reactions are rapid under neutral to slightly alkaline conditions, and proceed at low temperatures and dilutions. The implications of these findings for the origin of life are discussed.

Implications for the formation of abasic sites following modification of polydeoxycytidylic acid by acrolein in vitro

International Nuclear Information System (INIS)

Smith, R.A.; Sysel, I.A.; Tibbels, T.S.; Cohen, S.M.

1988-01-01

Polydeoxycytidylic acid (poly dC) was incubated with excess acrolein. A Nensorb 20 nucleic acid purification cartridge was used to bind the polymeric material in the poly dC/acrolein reaction mixture. The non-polymeric material eluted from this column had a UV absorbance four times higher than that of the control. The flourescence spectrum of the eluted material did not correspond to that of unmodified cytosine. Separate aliquots of the reaction mixture were digested to deoxynucleotide 3 ' -monophosphates by incubation with micrococcal nuclease and spleen phosphodiesterase. The products were converted to 3 2P-labelled deoxynucleotide 3 ' ,5-biphosphates by incubation with T4 polynucleotide kinase and excess [γ- 3 2P]ATP. The ' -monophosphate was selectively removed by incubation with nuclease P1. Two dimensional thin-layer chromatography (TLC) on polyethyleneimine cellulose (PEI)-cellulose and detection of 3 2P-labeled deoxynucleotide 5 ' -monophosphates by autoradiography failed to provide evidence for the formation of an acrolein adduct of deoxycytidine 5'-monophosphate. When acrolein-modified deoxycytidine 5 ' -monophosphate, was detected. These data show that acrolein-modified deoxycytidine 3 ' -monophosphates are substrates for 3 2P labeling by T4 polynucleotide kinase and are stable under the assay conditions employed

Acrolein-mediated conduction loss is partially restored by K+ channel blockers

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Yan, Rui; Page, Jessica C.

2015-01-01

Acrolein-mediated myelin damage is thought to be a critical mechanism leading to conduction failure following neurotrauma and neurodegenerative diseases. The exposure and activation of juxtaparanodal voltage-gated K+ channels due to myelin damage leads to conduction block, and K+ channel blockers have long been studied as a means for restoring axonal conduction in spinal cord injury (SCI) and multiple sclerosis (MS). In this study, we have found that 100 μM K+ channel blockers 4-aminopyridine-3-methanol (4-AP-3-MeOH), and to a lesser degree 4-aminopyridine (4-AP), can significantly restore compound action potential (CAP) conduction in spinal cord tissue following acrolein-mediated myelin damage using a well-established ex vivo SCI model. In addition, 4-AP-3-MeOH can effectively restore CAP conduction in acrolein-damaged axons with a range of concentrations from 0.1 to 100 μM. We have also shown that while both compounds at 100 μM showed no preference of small- and large-caliber axons when restoring CAP conduction, 4-AP-3-MeOH, unlike 4-AP, is able to augment CAP amplitude while causing little change in axonal responsiveness measured in refractory periods and response to repetitive stimuli. In a prior study, we show that 4-AP-3-MeOH was able to functionally rescue mechanically injured axons. In this investigation, we conclude that 4-AP-3-MeOH is an effective K+ channel blocker in restoring axonal conduction following both primary (physical) and secondary (chemical) insults. These findings also suggest that 4-AP-3-MeOH is a viable alternative of 4-AP for treating myelin damage and improving function following central nervous system trauma and neurodegenerative diseases. PMID:26581866

Polarographic study of acrolein and its determination by flow injection with amperometric detection at a mercury electrode.

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Naranjo Rodríguez, I; Muñoz Leyva, J A; Hidalgo Hidalgo de Cisneros, J L

1996-07-01

A study of the electrochemical behavior of acrolein at a dropping mercury electrode using different polarographic techniques is described. Theoretical studies of the reversibility of the wave of acrolein were carried out using two different polarographic techniques: direct current tast and differential pulse. Differential pulse polarography may be used to determine acrolein concentration in a Britton-Robinson buffer solution of pH 10 in the ranges 2 x 10(-7)10(-8) and 5 x 10(-8)-10(-4) mol dm(-3) and a coefficient of variation of 1.7% for a concentration of 10(-5)mol dm(-3). A flow injection method with amperometric detection at a potential of -1.4V using a mercury electrode is also described. Before each injection, any drop hanging from the tip of the capillary needs to be dislodged and a new electrode drop dispensed; three different drop sizes were tested. A linear relationship between peak intensity and acrolein concentration was obtained in the range 10(-5)-10(-7) mol dm(-3), with a detection limit of 9.8 x 10(-8) mol dm(-) 3 and a coefficient of variation of 2.9% for a 2 x 10(-7) mol dm(-3) concentration. Several organic and inorganic species were tested in order to ascertain whether they interfered with the signal for acrolein. The proposed methods were applied to the determination of acrolein in seawater samples.

Polyphenol extract from Phellinus igniarius protects against acrolein toxicity in vitro and provides protection in a mouse stroke model.

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Suabjakyong, Papawee; Saiki, Ryotaro; Van Griensven, Leo J L D; Higashi, Kyohei; Nishimura, Kazuhiro; Igarashi, Kazuei; Toida, Toshihiko

2015-01-01

The basidiomycetous mushroom Phellinus igniarius (L.) Quel. has been used as traditional medicine in various Asian countries for many years. Although many reports exist on its anti-oxidative and anti-inflammatory activities and therapeutic effects against various diseases, our current knowledge of its effect on stroke is very limited. Stroke is a neurodegenerative disorder in which oxidative stress is a key hallmark. Following the 2005 discovery by Igarashi's group that acrolein produced from polyamines in vivo is a major cause of cell damage by oxidative stress, we now describe the effects of anti-oxidative extracts from P. igniarius on symptoms of experimentally induced stroke in mice. The toxicity of acrolein was compared with that of hydrogen peroxide in a mouse mammary carcinoma cell line (FM3A). We found that the complete inhibition of FM3A cell growth by 5 μM acrolein could be prevented by crude ethanol extract of P. igniarius at 0.5 μg/ml. Seven polyphenol compounds named 3,4-dihydroxybenzaldehyde, 4-(3,4-dihydroxyphenyl-3-buten-2one, inonoblin C, phelligridin D, inoscavin C, phelligridin C and interfungin B were identified from this ethanolic extract by LCMS and 1H NMR. Polyphenol-containing extracts of P. igniarius were then used to prevent acrolein toxicity in a mouse neuroblastoma (Neuro-2a) cell line. The results suggested that Neuro-2a cells were protected from acrolein toxicity at 2 and 5 μM by this polyphenol extract at 0.5 and 2 μg/ml, respectively. Furthermore, in mice with experimentally induced stroke, intraperitoneal treatment with P. igniarius polyphenol extract at 20 μg/kg caused a reduction of the infarction volume by 62.2% compared to untreated mice. These observations suggest that the polyphenol extract of P. igniarius could serve to prevent ischemic stroke.

A Possible Role of Acrolein in Diabetic Retinopathy: Involvement of a VEGF/TGFβ Signaling Pathway of the Retinal Pigment Epithelium in Hyperglycemia

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Grigsby, Jeffery; Betts, Brandi; Vidro-Kotchan, Eileen; Culbert, Richard; Tsin, Andrew

2015-01-01

Purpose Acrolein has been implicated in retinal pigment epithelium (RPE) cell death, and has been associated with diabetic retinopathy. Our purpose was to investigate the potential effect of high glucose in influencing acrolein-mediated RPE cytokine production and cell death. We investigated the influence of the acrolein effect on ARPE-19 cells in high glucose conditions and quantified the release of transforming growth factor β (TGFβ1 and 2) and vascular endothelial growth factor (VEGF). We assessed the ability of N-benzylhydroxylamine(NBHA) as well as TGFβ pathway inhibitors SIS3 and SB431542 to prevent this effect of acrolein on ARPE-19 cells. Materials and methods Confluent ARPE-19 cells were treated with acrolein and/or NBHA in both 5.5 and 18.8 mM glucose conditions. Cells were also pretreated with SIS3, a specific inhibitor of the SMAD3 pathway, and SB431542, a specific inhibitor of TGFβ signaling pathway, before treating them with acrolein. Viable cells were counted and ELISAs were performed to measure the cytokines TGFβ1 and 2, and VEGF released into the conditioned media. Results In ARPE-19 cells exposed to acrolein and hyperglycemia there was reduced cell viability and an increase in the cell media of VEGF, TGFβ1, and TGFβ2, which was reversed by NBHA. Acrolein/hyperglycemia-induced cell viability reduction and cytokine overproduction was also reduced by TGFβ pathway blockade. Conclusions We conclude that the effect of acrolein on the reduction of viability and VEGF increase by ARPE-19 cells in hyperglycemic media is conducted through the TGFβ signaling pathway. Our results suggest that benefits of sequestering acrolein by NBHA and the blockage of the TGFβ pathway by SB431542 and SIS3 offer suggestions as to potential useful pharmacological drug candidates for the prevention of diabetes-induced complications in the eye. PMID:22906079

A possible role of acrolein in diabetic retinopathy: involvement of a VEGF/TGFβ signaling pathway of the retinal pigment epithelium in hyperglycemia.

Science.gov (United States)

Grigsby, Jeffery; Betts, Brandi; Vidro-Kotchan, Eileen; Culbert, Richard; Tsin, Andrew

2012-11-01

Acrolein has been implicated in retinal pigment epithelium (RPE) cell death, and has been associated with diabetic retinopathy. Our purpose was to investigate the potential effect of high glucose in influencing acrolein-mediated RPE cytokine production and cell death. We investigated the influence of the acrolein effect on ARPE-19 cells in high glucose conditions and quantified the release of transforming growth factor β (TGFβ1 and 2) and vascular endothelial growth factor (VEGF). We assessed the ability of N-benzylhydroxylamine(NBHA) as well as TGFβ pathway inhibitors SIS3 and SB431542 to prevent this effect of acrolein on ARPE-19 cells. Confluent ARPE-19 cells were treated with acrolein and/or NBHA in both 5.5 and 18.8 mM glucose conditions. Cells were also pretreated with SIS3, a specific inhibitor of the SMAD3 pathway, and SB431542, a specific inhibitor of TGFβ signaling pathway, before treating them with acrolein. Viable cells were counted and ELISAs were performed to measure the cytokines TGFβ1 and 2, and VEGF released into the conditioned media. In ARPE-19 cells exposed to acrolein and hyperglycemia there was reduced cell viability and an increase in the cell media of VEGF, TGFβ1, and TGFβ2, which was reversed by NBHA. Acrolein/hyperglycemia-induced cell viability reduction and cytokine overproduction was also reduced by TGFβ pathway blockade. We conclude that the effect of acrolein on the reduction of viability and VEGF increase by ARPE-19 cells in hyperglycemic media is conducted through the TGFβ signaling pathway. Our results suggest that benefits of sequestering acrolein by NBHA and the blockage of the TGFβ pathway by SB431542 and SIS3 offer suggestions as to potential useful pharmacological drug candidates for the prevention of diabetes-induced complications in the eye.

The dimers of glyoxal and acrolein with H 2O and HF: Negative intramolecular coupling and blue-shifted C-H stretch

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Karpfen, Alfred; Kryachko, Eugene S.

2010-04-01

The structures and the vibrational spectra of the hydrogen-bonded complexes: glyoxal-H 2O, glyoxal-HF, acrolein-H 2O, and acrolein-HF, are investigated within the MP2/aug-cc-pVTZ computational approach. It is demonstrated that the calculated blue shifts of the C-H stretching frequencies in the glyoxal-H 2O complexes are only indirectly pertinent to hydrogen bonding to the C-H group. The comparison with the glyoxal-HF and the acrolein-HF complexes reveals that these blue shifts are a direct consequence of a negative intramolecular coupling between vicinal C dbnd O and C-H bonds in the aldehyde groups of isolated glyoxal and acrolein molecules. To support this interpretation, the halogen-bonded complexes glyoxal-BrF and acrolein-BrF are discussed.

Acrolein involvement in sensory and behavioral hypersensitivity following spinal cord injury in the rat

OpenAIRE

Due, Michael R.; Park, Jonghyuck; Zheng, Lingxing; Walls, Michael; Allette, Yohance M.; White, Fletcher A.; Shi, Riyi

2013-01-01

Growing evidence suggests that oxidative stress, as associated with spinal cord injury (SCI), may play a critical role in both neuroinflammation and neuropathic pain conditions. The production of the endogenous aldehyde acrolein, following lipid peroxidation during the inflammatory response, may contribute to peripheral sensitization and hyperreflexia following SCI via the TRPA1-dependent mechanism. Here we report that there are enhanced levels of acrolein and increased neuronal sensitivity t...

A single exposure to acrolein causes arrhythmogenesis, cardiac electrical dysfunction and decreased heart rate variability in hypertensive rats

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Epidemiological studies demonstrate an association between cardiovascular morbidity, arrhythmias, and exposure to air toxicants such as acrolein. We hypothesized that a single exposure to acrolein would increase arrhythmias and cause changes in the electrocardiogram (ECG) of hype...

Acrolein with an alpha, beta-unsaturated Carbonyl Group Inhibits LPS-induced Homodimerization of Toll-like Receptor 4

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Acrolein is a highly electrophilic a,ß-unsaturated aldehyde present in a number of environmental sources, especially cigarette smoke. It reacts strongly with the thiol groups of cysteine residues by Michael addition and has been reported to inhibit nuclear factor-kB (NF-kB) activation by lipopolysac...

Cyclophosphamide and acrolein induced oxidative stress leading to deterioration of metaphase II mouse oocyte quality.

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Jeelani, Roohi; Khan, Sana N; Shaeib, Faten; Kohan-Ghadr, Hamid-Reza; Aldhaheri, Sarah R; Najafi, Tohid; Thakur, Mili; Morris, Robert; Abu-Soud, Husam M

2017-09-01

Cyclophosphamide (CTX) is a chemotherapeutic agent widely used to treat ovarian, breast, and hematological cancers as well as autoimmune disorders. Such chemotherapy is associated with reproductive failure and premature ovarian insufficiency. The mechanism by which CTX and/or its main metabolite, acrolein, affect female fertility remains unclear, but it is thought to be caused by an overproduction of reactive oxygen species (ROS). Here, we investigated the effect of CTX on metaphase II mouse oocytes obtained from treated animals (120mg/kg, 24h of single treatment), and oocytes directly exposed to increasing concentrations of CTX and acrolein (n=480; 0, 5, 10, 25, 50, and 100μM) with and without cumulus cells (CCs) for 45min which correlates to the time of maximum peak plasma concentrations after administration. Oocytes were fixed and subjected to indirect immunofluorescence and were scored based on microtubule spindle structure (MT) and chromosomal alignment (CH). Generation of ROS was evaluated using the Cellular Reactive Oxygen Species Detection Assay Kit. Deterioration of oocyte quality was noted when oocytes were obtained from CTX treated mice along with CTX and acrolein treated oocytes in a dose-dependent manner as shown by an increase in poor scores. Acrolein had an impact at a significantly lower level as compared to CTX, plateau at 10μM versus 50μM, respectively. These variation is are associated with the higher amount of ROS generated with acrolein exposure as compared to CTX (pacrolein scavengers may mitigate the damaging effects of these compounds and help women undergoing such treatment. Copyright © 2017. Published by Elsevier Inc.

Acrolein inhalation causes myocardial strain delay and decreased cardiac performance as detected by high-frequency echocardiography in mice

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Acrolein, an unsaturated aldehyde found in air pollution, impairs Ca2+ flux and contraction in cardiomyocytes in vitro. To better define direct and delayed functional cardiac effects, we hypothesized that a single exposure to acrolein would modify myocardial strain and performanc...

Determination of acrolein in serum by high-performance liquid chromatography with fluorescence detection after pre-column fluorogenic derivatization using 1,2-diamino-4,5-dimethoxybenzene.

Science.gov (United States)

Imazato, Takahiro; Kanematsu, Mariko; Kishikawa, Naoya; Ohyama, Kaname; Hino, Takako; Ueki, Yukitaka; Maehata, Eisuke; Kuroda, Naotaka

2015-09-01

Acrolein is a major unsaturated aldehyde that is generated during the lipid peroxidation process. The measurement of acrolein in biological samples should be useful to estimate the degree of lipid peroxidation and to evaluate the effect of hazardous properties of acrolein on human health. In this study, a highly sensitive and selective high-performance liquid chromatography with fluorescence detection method was developed for the determination of acrolein in human serum. The proposed method involves the pre-column fluorogenic derivatization of acrolein with 1,2-diamino-4,5-dimethoxybenzene (DDB) as a reagent. The fluorescent derivative of acrolein could be detected clearly without any interfering reagent blank peaks because DDB does not have intrinsic fluorescence itself, and the detection limit was 10 nM (signal-to-noise ratio = 3). The proposed method could selectively detect acrolein in human serum with a simple protein precipitation treatment. Copyright © 2015 John Wiley & Sons, Ltd.

A comparative review of petroleum-based and bio-based acrolein production.

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Liu, Lu; Ye, X Philip; Bozell, Joseph J

2012-07-01

Acrolein is an important chemical intermediate for many common industrial chemicals, leading to an array of useful end products. This paper reviews all the synthetic methods, including the former (aldol condensation) and contemporary (partial oxidation of propylene) manufacturing methods, the partial oxidation of propane, and most importantly, the bio-based glycerol-dehydration route. Emphasis is placed on the petroleum-based route from propylene and the bio-based route from glycerol, an abundantly available and relatively inexpensive raw material available from biodiesel production. This review provides technical details and incentives for industrial proyduction that justify a transition toward bio-based acrolein production. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

On the performance of quantum chemical methods to predict solvatochromic effects. The case of acrolein in aqueous solution

DEFF Research Database (Denmark)

Aidas, Kestutis; Møgelhøj, Andreas; Nilsson, Elna Johanna Kristina

2008-01-01

The performance of the Hartree–Fock method and the three density functionals B3LYP, PBE0, and CAM-B3LYP is compared to results based on the coupled cluster singles and doubles model in predictions of the solvatochromic effects on the vertical n¿* and ¿* electronic excitation energies of acrolein...... of acrolein in vapor phase and aqueous solution. The gas-to-aqueous solution shift of the n¿* excitation energy is well reproduced by using all density functional methods considered. However, the B3LYP and PBE0 functionals completely fail to describe the ¿* electronic transition in solution, whereas...... the recent CAM-B3LYP functional performs well also in this case. The ¿* excitation energy of acrolein in water solution is found to be very dependent on intermolecular induction and nonelectrostatic interactions. The computed excitation energies of acrolein in vacuum and solution compare well to experimental...

Acute and long-term ocular effects of acrolein vapor on the eyes and potential therapies.

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Dachir, Shlomit; Cohen, Maayan; Gutman, Hila; Cohen, Liat; Buch, Hillel; Kadar, Tamar

2015-01-01

Acrolein is a potent irritant and a vesicant that was used by the French during WWI as the warfare agent named: "papite". Nowadays, it is produced in large amounts all over the world in the industry for the production of acrylic acid and for agriculture use as herbicide. The aim of this study was to characterize the effects of acute eye exposure to acrolein vapor and to evaluate the efficacy of a topical post-exposure combination treatment with a local anesthetic and a steroid. Rabbit eyes were exposed to three doses of acrolein vapor (low, intermediate and high) and treated topically with either 0.4% benoxinate hydrochloride (localin, for 2 h) or dexamethasone (dexamycin, for 6 days) or a combination of both drugs. Clinical follow-up using slit lamp examinations and histological evaluation was performed 4 weeks post-exposure. Acrolein vapor caused immediate eye closure with excess tearing, corneal erosions and severe inflammation of the anterior chamber. This was followed by corneal neovascularization (NV) starting as early as 1 week post-exposure. The damage to the eyes was long lasting, and at 4 weeks following exposure, significant pathological changes were observed. Immediate post-exposure application of the local anesthetic, localin, prevented the eye closure, and the dexamycin treatment reduced significantly the initial inflammation as well as the extent and incidence of corneal NV. Short-term eye exposure to the irritant acrolein may result in immediate eye closure and long lasting pathologies that could lead to blindness. An anti-inflammatory treatment combined with short-term application of a local anesthetic prevents incapacitation and might minimize significantly the extent of eye injuries.

Infrared multiphoton dissociation of acrolein. Time-resolved observation of CO ( v = 1) IR emission at 4.7 μm

Science.gov (United States)

Chowdhury, P. K.; Rama Rao, K. V. S.; Mittal, J. P.

1994-02-01

In contrast to the photochemistry of electronically excited acrolein producing vinyl and formyl radicals via CC bond rupture, multiphoton vibrationally excited molecules undergo concerted dissociation generating CO and ethylene. Vibrational excitation in the CO product is detected immediately following the CO 2 laser pulse by observing IR emission at 4.7 μm. The decay of the IR emission was studied as a function of acrolein pressure. A vibrational-vibrational relaxation rate constant of CO ( v=1) by acrolein is found to be 1240 ± 200 Torr -1 s -1.

CO product energy distribution in the photodissociation of methylketene and acrolein at 193 nm

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Fujimoto, G. T.; Umstead, M. E.; Lin, M. C.

1985-04-01

CO product vibrational energy distributions in the photodissociation of the two C3H4O isomers, methylketene (CH3CHCO) and acrolein (CH2CHCHO), at 193 nm have been measured by CO laser resonance absorption. The CO from methylketene was found to be vibrationally excited up to v=7, and from acrolein v=6, with average vibrational energies of 3.4±0.3 and 2.7±0.7 kcal/mol, respectively. The similarities observed in the appearance times and in the vibrational energy content of the CO formed in the two systems support our previous conclusion that in the case of acrolein isomerization to methylketene takes place prior to the dissociation process: CH2CHCHO+hν→CH3CHCO*†→CH3CH+CO†. The CO vibrational energy distributions observed in both systems agree closely with the statistical distribution predicted assuming that ethylidene rather than ethylene is formed in the photodissociation reaction.

Theoretical studies of acrolein hydrogenation on Au20 nanoparticle

Science.gov (United States)

Li, Zhe; Chen, Zhao-Xu; He, Xiang; Kang, Guo-Jun

2010-05-01

Gold nanoparticles play a key role in catalytic processes. We investigated the kinetics of stepwise hydrogenation of acrolein on Au20 cluster model and compared with that on Au(110) surface. The rate-limiting step barrier of CC reduction is about 0.5 eV higher than that of CO hydrogenation on Au(110) surface. On Au20 nanoparticle, however, the energy barrier of the rate-determining step for CC hydrogenation turns out to be slightly lower than the value for the CO reduction. The selectivity difference on the two substrate models are attributed to different adsorption modes of acrolein: via the CC on Au20, compared to through both CC and CO on Au(110). The preference switch implies that the predicted selectivity of competitive hydrogenation depends on substrate model sensitively, and particles with more low-coordinated Au atoms than flat surfaces are favorable for CC hydrogenation, which is in agreement with experimental result.

Acrolein Disrupts Tight Junction Proteins and Causes Endoplasmic Reticulum Stress-Mediated Epithelial Cell Death Leading to Intestinal Barrier Dysfunction and Permeability.

Science.gov (United States)

Chen, Wei-Yang; Wang, Min; Zhang, Jingwen; Barve, Shirish S; McClain, Craig J; Joshi-Barve, Swati

2017-12-01

Increasing evidence suggests that environmental and dietary factors can affect intestinal epithelial integrity leading to gut permeability and bacterial translocation. Intestinal barrier dysfunction is a pathogenic process associated with many chronic disorders. Acrolein is an environmental and dietary pollutant and a lipid-derived endogenous metabolite. The impact of acrolein on the intestine has not been investigated before and is evaluated in this study, both in vitro and in vivo. Our data demonstrate that oral acrolein exposure in mice caused damage to the intestinal epithelial barrier, resulting in increased permeability and subsequently translocation of bacterial endotoxin-lipopolysaccharide into the blood. Similar results were seen in vitro using established Caco-2 cell monolayers wherein acrolein decreased barrier function and increased permeability. Acrolein also caused the down-regulation and/or redistribution of three representative tight junction proteins (ie, zonula occludens-1, Occludin, Claudin-1) that critically regulate epithelial paracellular permeability. In addition, acrolein induced endoplasmic reticulum stress-mediated death of epithelial cells, which is an important mechanism contributing to intestinal barrier damage/dysfunction, and gut permeability. Overall, we demonstrate that exposure to acrolein affects the intestinal epithelium by decrease/redistribution of tight junction proteins and endoplasmic reticulum stress-mediated epithelial cell death, thereby resulting in loss of barrier integrity and function. Our findings highlight the adverse consequences of environmental and dietary pollutants on intestinal barrier integrity/function with relevance to gut permeability and the development of disease. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

NMR investigation of acrolein stability in hydroalcoholic solution as a foundation for the valid HS-SPME/GC–MS quantification of the unsaturated aldehyde in beverages

International Nuclear Information System (INIS)

Kächele, Martin; Monakhova, Yulia B.; Kuballa, Thomas; Lachenmeier, Dirk W.

2014-01-01

Highlights: • Acrolein in hydroalcoholic solution degrades to 1,3,3-propanetriol and 3-hydroxypropionaldehyde. • Hydroquinone (0.2%) at pH 3.0 stabilizes acrolein solutions. • Quantitative HS-SPME/GC–MS determination of acrolein in alcoholic beverages was developed (LOD 14 μg L −1 ). • 6 of 117 samples had acrolein levels above the WHO threshold (1500 μg L −1 ). - Abstract: Acrolein (propenal) is found in many foods and beverages and may pose a health hazard due to its cytotoxicity. Considerable knowledge gaps regarding human exposure to acrolein exist, and there is a lack of reliable analytical methods. Hydroalcoholic dilutions prepared for calibration purposes from pure acrolein show considerable degradation of the compound and nuclear magnetic resonance (NMR) spectroscopy showed that 1,3,3-propanetriol and 3-hydroxypropionaldehyde are formed. The degradation can be prevented by addition of hydroquinone as stabilizer to the calibration solutions, which then show linear concentration-response behaviour required for quantitative analysis. The stabilized calibration solutions were used for quantitative headspace solid-phase microextraction/gas chromatography–mass spectrometry (HS-SPME/GC–MS) determination of acrolein in alcoholic beverages with a detection limit of 14 μg L −1 . Of 117 tested alcoholic beverages, 64 were tested positive with the highest incidence in grape marc spirits and whiskey (100%, mean 252 μg L −1 ), followed by fruit spirits (86%, mean 591 μg/L −1 ), tequila (86%, mean 404 μg L −1 ), Asian spirits (43%, mean 54 μg L −1 ) and wine (9%, mean 0.7 μg L −1 ). Acrolein could not be detected in beer, vodka, absinthe and bottled water. Six of the fruit and grape marc spirits had acrolein levels above the World Health Organization (WHO) provisional tolerable concentration of 1.5 mg L −1

NMR investigation of acrolein stability in hydroalcoholic solution as a foundation for the valid HS-SPME/GC–MS quantification of the unsaturated aldehyde in beverages

Energy Technology Data Exchange (ETDEWEB)

Kächele, Martin [Chemisches und Veterinäruntersuchungsamt (CVUA) Karlsruhe, Weissenburger Strasse 3, D-76187 Karlsruhe (Germany); Hochschule Mannheim, Paul-Wittsack-Strasse 10, D-68163 Mannheim (Germany); Monakhova, Yulia B. [Chemisches und Veterinäruntersuchungsamt (CVUA) Karlsruhe, Weissenburger Strasse 3, D-76187 Karlsruhe (Germany); Bruker Biospin GmbH, Silbersteifen, 76287 Rheinstetten (Germany); Department of Chemistry, Saratov State University, Astrakhanskaya Street 83, 410012 Saratov (Russian Federation); Kuballa, Thomas [Chemisches und Veterinäruntersuchungsamt (CVUA) Karlsruhe, Weissenburger Strasse 3, D-76187 Karlsruhe (Germany); Lachenmeier, Dirk W., E-mail: lachenmeier@web.de [Chemisches und Veterinäruntersuchungsamt (CVUA) Karlsruhe, Weissenburger Strasse 3, D-76187 Karlsruhe (Germany); Ministry of Rural Affairs and Consumer Protection, Kernerplatz 10, 70182 Stuttgart (Germany)

2014-04-01

Highlights: • Acrolein in hydroalcoholic solution degrades to 1,3,3-propanetriol and 3-hydroxypropionaldehyde. • Hydroquinone (0.2%) at pH 3.0 stabilizes acrolein solutions. • Quantitative HS-SPME/GC–MS determination of acrolein in alcoholic beverages was developed (LOD 14 μg L⁻¹. • 6 of 117 samples had acrolein levels above the WHO threshold (1500 μg L⁻¹). Abstract: Acrolein (propenal) is found in many foods and beverages and may pose a health hazard due to its cytotoxicity. Considerable knowledge gaps regarding human exposure to acrolein exist, and there is a lack of reliable analytical methods. Hydroalcoholic dilutions prepared for calibration purposes from pure acrolein show considerable degradation of the compound and nuclear magnetic resonance (NMR) spectroscopy showed that 1,3,3-propanetriol and 3-hydroxypropionaldehyde are formed. The degradation can be prevented by addition of hydroquinone as stabilizer to the calibration solutions, which then show linear concentration-response behaviour required for quantitative analysis. The stabilized calibration solutions were used for quantitative headspace solid-phase microextraction/gas chromatography–mass spectrometry (HS-SPME/GC–MS) determination of acrolein in alcoholic beverages with a detection limit of 14 μg L⁻¹. Of 117 tested alcoholic beverages, 64 were tested positive with the highest incidence in grape marc spirits and whiskey (100%, mean 252 μg L⁻¹), followed by fruit spirits (86%, mean 591 μg/L⁻¹), tequila (86%, mean 404 μg L⁻¹), Asian spirits (43%, mean 54 μg L⁻¹) and wine (9%, mean 0.7 μg L⁻¹). Acrolein could not be detected in beer, vodka, absinthe and bottled water. Six of the fruit and grape marc spirits had acrolein levels above the World Health Organization (WHO) provisional tolerable concentration of 1.5 mg L⁻¹.

Acrolein coupling on reduced TiO 2(1 1 0): The effect of surface oxidation and the role of subsurface defects

Science.gov (United States)

Benz, Lauren; Haubrich, Jan; Quiller, Ryan G.; Friend, Cynthia M.

2009-04-01

Reactions of acrolein, water, and oxygen with the vacuum-reduced surface of TiO 2(1 1 0) are reported in a temperature programmed reaction study of the interaction of an aldehydic pollutant with a reducible metal oxide. A total of 25% of the acrolein that binds to the surface is converted to products. Notably, carbon-carbon coupling occurs with 86% selectivity for formation of C 6 products: C 6H 8, identified as 1,3-cyclohexadiene, in a peak at 500 K and benzene immediately thereafter at 530 K. Acrolein is evolved from the surface in three peaks: a peak independent of coverage at 495 K, attributed to decomposition of an intermediate that is partly converted to C 6H 8; a coverage-dependent peak that shifts from 370 K (low coverage) to 260 K (high coverage), which is attributed to adsorption at 5-fold coordinated Ti sites; and a multilayer state at 160 K. Water and acrolein compete for 5-fold coordinated titanium sites when dosed sequentially. The addition of water also opens a new reaction pathway, leading to the hydrogenation of acrolein to form propanal. Water has no effect on the yield of 1,3-cyclohexadiene. Exposure of the surface to oxygen prior to acrolein dosing quenches the evolution of acrolein at 495 K and concurrently eliminates the coupling. From these results, we propose that reduced subsurface defects such as titanium ion interstitials play a role in the reactions observed here. The notion that subsurface defects may contribute to the reactivity of organic molecules over reducible oxide substrates may prove to be general.

Glycerol valorization: dehydration to acrolein over silica-supported niobia catalysts

NARCIS (Netherlands)

Shiju, N.R.; Brown, D.R.; Wilson, K.; Rothenberg, G.

2010-01-01

The catalytic dehydration of glycerol to acrolein is investigated over silica-supported niobia catalysts in a continuous fixed-bed gas-phase reactor. Various supported niobia catalysts are prepared and characterized using surface analysis and spectroscopic methods (XRD, UV-Vis, XPS, N2 adsorption),

Protective effects of the aqueous extract of Scutellaria baicalensis against acrolein-induced oxidative stress in cultured human umbilical vein endothelial cells.

Science.gov (United States)

Zhang, Xing-Wei; Li, Wei-Fen; Li, Wei-Wei; Ren, Kan-Han; Fan, Chao-Ming; Chen, Ying-Ying; Shen, Yue-Liang

2011-03-01

 Scutellaria baicalensis Georgi (Labiatae) (SbG), one of the fifty fundamental herbs of Chinese herbology, has been reported to have anti-asthmatic, antifungal, antioxidative, and anti-inflammatory activities.  This study was designed to determine the protective effects of the extract of SbG against the acrolein-induced oxidative stress in cultured human umbilical vein endothelial cells (HUVEC).  The MTT reduction assay was employed to determine cell viability. The total cellular glutathione (GSH) level was detected using a colorimetric GSH assay kit. Cellular GSH production was conducted by detecting the mRNA expression levels of γ-glutamylcysteine ligase catalytic subunit and modifier subunit.  Concentration-dependent cytotoxic effects of acrolein were observed while SbG could effectively protect the acrolein-induced oxidative damage. The protective mechanism was investigated, showing that the increased GSH content in the SbG-incubated HUVE cells was associated with the protective effects of SbG-treated cells. Further RT-PCR data confirmed the elevated mRNA expressions of GSH synthesis enzymes.  The current study strongly indicated that SbG could be a potential antioxidant against oxidative stress in treating cardiovascular diseases.

Acrolein produces nitric oxide through the elevation of intracellular calcium levels to induce apoptosis in human umbilical vein endothelial cells: implications for smoke angiopathy.

Science.gov (United States)

Misonou, Yoshiko; Asahi, Michio; Yokoe, Shunichi; Miyoshi, Eiji; Taniguchi, Naoyuki

2006-03-01

Acrolein is a highly electrophilic alpha, beta-unsaturated aldehyde, the levels of which are increased in the blood of smokers. To determine if acrolein is involved in the pathology of smoke angiopathy, the effect of acrolein on human umbilical vein endothelial cells (HUVEC) was examined. Intracellular nitric oxide (NO) levels, determined using diaminofluorescein-2 diacetate (DAF-2 DA), an NO sensitive fluorescent dye, were found to be increased after treatment in HUVEC with 10 microM acrolein. The measurement of nitrite with 2,3-diaminonaphthalene and a Western blot analysis revealed that nitrite and S-nitroso-cysteine levels were increased in a dose-dependent manner, confirming that NO production is increased by acrolein. The increase was not reduced by treatment with 10mM N-acetyl-l-cysteine (NAC), an anti-oxidant, but was reduced with 10 microM of the intracellular calcium chelator, 1,2-bis (o-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid tetra (acetoxymethyl) ester. Acrolein-stimulated NO production was significantly reduced by pretreatment with 1mM N(G)-nitro-l-arginine-methyl ester (L-NAME), an NO synthase inhibitor. The cytotoxicity of acrolein was reduced by pretreatment with 10 microM 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (carboxy-PTIO), an intracellular NO scavenger, or 1mM L-NAME, whereas it was not reduced by 10mM NAC, 20 microM Curcumin, another peroxide scavenger, or 100 microM Mn(III)TMPyP, a superoxide dismutase mimic. Nuclear staining and a Western blot analysis using an anti-cleaved caspase 3 antibody revealed that the reduced viability of HUVEC by acrolein was due to apoptosis, which was reversed after pretreatment with 0.1mM carboxy-PTIO or 1mM L-NAME. Thus, acrolein increases intracellular calcium production to induce intracellular NO production by a calcium-dependent NO synthase, possibly eNOS, and the excess and rapid increase in NO might lead to the apoptosis of HUVEC. These data suggest that acrolein might be

[Changes of CD(4)(+) Foxp3+ regulatory T cells and CD(4)(+)IL-17+T cells in acrolein exposure rats].

Science.gov (United States)

Wei, Ming; Tu, Ling; Liang, Yinghong; Li, Jia; Gong, Yanjie; Zhang, Yihua; Yang, Lu

2015-09-01

To evaluate the changes of CD(4)(+) IL-17+T (Th17) and CD(4)(+)Foxp3+regulatory T (Treg) cells in peripheral blood and bronchoalveolar lavage fluid (BALF) , and therefore to explore the role of Th17 and Treg in acrolein exposure airway inflammation in rats. Forty male Wistar rats were randomly divided into 4 groups: a 2 wk acrolein exposure group, a 4 wk acrolein exposure group, a 2 wk control group and a 4 wk control group (n=10 each). Cells in BALF were collected and analyzed by absolute and differential cell counts.IL-17 and IL-6 levels in serum and BALF were tested by enzyme linked immunosorbent assay (ELISA). The proportion of CD(4)(+)IL-17+T and CD(4)(+) Foxp3+Treg in peripheral blood and BALF were determined by flow cytometry.The mRNA expressions of IL-17 and Foxp3 were measured by real-time PCR. Comparisons of the data between different groups were performed using one-way ANOVA, and SNK and Games-Howell test were used for comparison between 2 groups. Levels of IL-17 were remarkable increased in the 2 wk acrolein exposure group and the 4 wk acrolein exposure group in serum [(52.64 ± 1.89) ng/L, (76.73 ± 5.57) ng/L], and BALF [(79.07 ± 5.67) ng/L, (96.61 ± 6.44) ng/L] compared with the 2 wk control group [(40.05 ± 3.12) ng/L, (56.75 ± 4.37) ng/L] and the 4 wk control group [(38.75 ± 3.23) ng/L, (53.27 ± 4.48) ng/L], all Pcells and macrophages (r=0.5126, 0.5437, all Pcells and an vary of inflammatory cytokines were evident in airway inflammation of acrolein exposed rats, suggesting that Treg was involved in the immunological regulation and Th17 was associated with the persistent inflammation in acrolein induced airway inflammation in rats.

Tissue sensitivity of the rat upper and lower extrapulmonary airways to the inhaled electrophilic air pollutants diacetyl and acrolein.

Science.gov (United States)

Cichocki, Joseph A; Smith, Gregory J; Morris, John B

2014-11-01

The target site for inhaled vapor-induced injury often differs in mouth-breathing humans compared with nose-breathing rats, thus complicating the use of rat inhalation toxicity data for assessment of human risk. We sought to examine sensitivity of respiratory/transitional nasal (RTM) and tracheobronchial (TBM) mucosa to two electrophilic irritant vapors: diacetyl and acrolein. Computational fluid dynamic physiologically based pharmacokinetic modeling was coupled with biomarker assessment to establish delivered dose-response relationships in RTM and TBM in male F344 rats following 6 h exposure to diacetyl or acrolein. Biomarkers included glutathione status, proinflammatory and antioxidant gene mRNA levels, and nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Modeling revealed that 0.0094-0.1653 μg acrolein/min-cm(2) and 3.9-21.6 μg diacetyl/min-cm(2) were deposited into RTM/TBM. Results indicate RTM and TBM were generally of similar sensitivity to diacetyl and acrolein. For instance, both tissues displayed induction of antioxidant and proinflammatory genes, and nuclear accumulation of Nrf2 after electrophile exposure. Hierarchical cellular response patterns were similar in RTM and TBM but differed between vapors. Specifically, diacetyl exposure induced proinflammatory and antioxidant genes concomitantly at low exposure levels, whereas acrolein induced antioxidant genes at much lower exposure levels than that required to induce proinflammatory genes. Generally, diacetyl was less potent than acrolein, as measured by maximal induction of transcripts. In conclusion, the upper and lower extrapulmonary airways are of similar sensitivity to inhaled electrophilic vapors. Dosimetrically based extrapolation of nasal responses in nose-breathing rodents may provide an approach to predict risk to the lower airways of humans during mouth-breathing. © The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology. All

The adsorption of acrolein on a Pt (1 1 1): A study of chemical bonding and electronic structure

Science.gov (United States)

Pirillo, S.; López-Corral, I.; Germán, E.; Juan, A.

2012-12-01

The adsorption of acrolein on a Pt (1 1 1) surface was studied using ab-initio and semiempirical calculations. Geometry optimization and densities of states (DOS) curves were carried out using the Vienna Ab-initio Simulation Package (VASP) code. We started our study with the preferential geometries corresponding to the different acrolein/Pt (1 1 1) adsorption modes previously reported. Then, we examined the evolution of the chemical bonding in these geometries, using the crystal orbital overlap population (COOP) and overlap population (OP) analysis of selected pairs of atoms. We analyzed the acrolein intramolecular bonds, Pt (1 1 1) superficial bonds and new moleculesbnd surface formed bonds after adsorption. We found that Ptsbnd Pt bonds interacting with the molecule and acrolein Cdbnd O and Cdbnd C bonds are weakened after adsorption; this last bond is significantly linked to the surface. The obtained Csbnd Pt and Osbnd Pt OP values suggest that the most stable adsorption modes are η3-cis and η4-trans, while the η1-trans is the less favored configuration. We also found that C pz orbital and Pt pz and d orbitals participate strongly in the adsorption process.

A SUBCHRONIC INHALATION STUDY OF FISCHER 344 RATS EXPOSED TO 0, 0.4, 1.4 OR 4.0 PPM ACROLEIN

International Nuclear Information System (INIS)

KUTZMAN, R.S.

1981-01-01

Fischer 344 rats were exposed to 0.0, 0.4, 1.4, or 4.0 ppm acrolein for 62 days. The major objective of the study was to relate the results of a series of pulmonary function tests to biochemical and pathological alterations observed in the lung. Cytological and reproductive potential endpoints were also assessed after acrolein exposure. Rats were exposed to acrolein for 6 hours/day, 5 days/week for 62 days. Mortality was observed only in the 4.0 ppm chamber where 32 of 57 exposed males died; however, none of the 8 exposed females died. Most of the mortality occurred within the first 10 exposure days. Histologic examination indicated that the animals died of acute bronchopneumonia. The surviving males and females exposed to 4.0 ppm acrolein gained weight at a significantly slower rate than control animals. The growth of both sexes in the 0.4 and 1.4 ppm groups was similar to that of their respective controls. Histopathologic examination of animals after 62 days of exposure revealed bronchiolar epithelial necrosis and sloughing, bronchiolar edema with macrophages, and focal pulmonary edema in the 4.0 ppm group. These lesions were, in some cases, associated with edema of the trachea and peribronchial lymph nodes, and acute rhinitis which indicated an upper respiratory tract effect of acrolein. Of particular interest was the variability of response between rats in the 4.0 ppm group, some not affected at all while others were moderately affected. Intragroup variability in toxicity was also apparent in the 1.4 ppm exposure group where only 3 of 31 animals examined had lesions directly related to acrolein exposure. Extra respiratory organs appeared unaffected

Respiratory Effects and Systemic Stress Response Following Acute Acrolein Inhalation in Rats

Data.gov (United States)

U.S. Environmental Protection Agency — This data set is an Excel file pertaining to the study that examined nasal, pulmonary, and systemic effects of acrolein in rats acutely exposed to a range of...

Protein alkylation, transcriptional responses and cytochrome c release during acrolein toxicity in A549 cells: influence of nucleophilic culture media constituents.

Science.gov (United States)

Thompson, Colin A; Burcham, Philip C

2008-06-01

Acrolein is a toxic combustion product that elicits apoptotic and/or necrotic cell death depending on the conditions under which exposure occurs. As a strong electrophile, side-reactions with nucleophilic media constituents seem likely to accompany study of its toxicity in vitro, but these reactions are poorly characterized. We have thus examined the effect of media composition on the toxicity of acrolein in A549 cells. Cells were exposed to acrolein in either Dulbecco's buffered saline (DBS) or F12 supplemented with various concentrations of fetal bovine serum. Cell viability was assessed using the MTT assay, while heme oxygenase-1 (HO-1) and cytoplasmic cytochrome c were measured as respective markers of transcriptional response and apoptosis. Protein damage was evaluated using the protein carbonyl assay. Compared to F12 media (with or without serum), maximal cell death as evaluated using the MTT assay, as well as adduction of intracellular proteins, occurred when cells were exposed to acrolein in DBS. In contrast, cytochrome c release was maximal in cells exposed to acrolein in serum-containing F12, conditions which inhibited protein modification and overt cell death. These findings highlight the need for careful attention to experimental conditions when conducting in vitro toxicological studies of reactive substances.

A theoretical investigation of valence and Rydberg electronic states of acrolein

International Nuclear Information System (INIS)

Aquilante, Francesco; Barone, Vincenzo; Roos, Bjoern O.

2003-01-01

The main features of the ultraviolet spectrum of acrolein have been studied by a multireference perturbative treatment and by a time dependent density functional approach. The valence and Rydberg transition energies have been calculated and the assignment of the experimental bands has been clarified. The different relaxation trends of the three lowest singlet and triplet excited states have been analyzed by unconstrained geometry optimizations. This has allowed, in particular, the characterization of a twisted 3 (ππ*) state, which is crucial for the interesting photophysics and photochemistry of the acrolein molecule and, more generally, of the α,β-enones. Solvatochromic shifts in aqueous solution have been investigated using a combined discrete/continuum approach based on the so called polarizable continuum model. The experimental trends are well reproduced by this approach and a closer degeneracy in the triplet manifold has been detected in solution with respect to gas phase

α,β-Unsaturated aldehyde pollutant acrolein suppresses cardiomyocyte contractile function: Role of TRPV1 and oxidative stress.

Science.gov (United States)

Wu, Zhenbiao; He, Emily Y; Scott, Glenda I; Ren, Jun

2015-01-01

Air pollution is associated with an increased prevalence of heart disease and is known to trigger a proinflammatory response via stimulation of transient receptor potential vanilloid cation channels (TRPV1, also known as the capsaicin receptor). This study was designed to examine the effect of acrolein, an essential α,β-unsaturated aldehyde pollutant, on myocardial contractile function and the underlying mechanism involved with a focus on TRPV1 and oxidative stress. Cardiomyocyte mechanical and intracellular Ca(2+) properties were evaluated using an IonOptix MyoCam® system including peak shortening (PS), maximal velocity of shortening/relengthening (± dL/dt), time-to-PS (TPS), time-to-90% relengthening (TR90 ), fura-2 fluorescence intensity (FFI) and intracellular Ca(2+) decay. Changes in apoptosis and TRPV1 were evaluated using Western blot analysis. The degree of oxidative stress was assessed using the ratio between reduced and oxidized glutathione. Results obtained revealed that exposure of cardiomyocytes to acrolein acutely compromised contractile and intracellular Ca(2+) properties including depressed PS, ± dL/dt and ΔFFI, as well as prolonged TR90 and intracellular Ca(2+) decay. In addition, acrolein exposure upregulated TRPV1 associated with an increase in both apoptosis and oxidative stress. However, the acrolein-induced cardiomyocyte contractile and intracellular Ca(2+) anomalies, as well as apoptosis (as evidenced by Bcl-2, Bax, FasL, Caspase-3 and -8), were negated by the reactive oxygen species (ROS) scavenger glutathione or the TRPV1 antagonist capsazepine. Collectively these data suggest that the α,β-unsaturated aldehyde pollutant acrolein may play a role in the pathogenesis and sequelae of air pollution-induced heart disease via a TRPV1- and oxidative stress-dependent mechanism. © 2013 Wiley Periodicals, Inc.

Levels of oxylipins, endocannabinoids and related lipids in plasma before and after low-level exposure to acrolein in healthy individuals and individuals with chemical intolerance.

Science.gov (United States)

Claeson, Anna-Sara; Gouveia-Figueira, Sandra; Häggström, Jenny; Fowler, Christopher J; Nording, Malin L

2017-06-01

Oxylipins and endocannabinoids play important biological roles, including effects upon inflammation. It is not known whether the circulating levels of these lipids are affected by inhalation of the environmental pollutant acrolein. In the present study, we have investigated the consequences of low-level exposure to acrolein on oxylipin, endocannabinoid and related lipid levels in the plasma of healthy individuals and individuals with chemical intolerance (CI), an affliction with a suggested inflammatory origin. Participants were exposed twice (60min) to heptane and a mixture of heptane and acrolein. Blood samples were collected before exposure, after and 24h post-exposure. There were no overt effects of acrolein exposure on the oxylipin lipidome or endocannibinoids detectable in the bloodstream at the time points investigated. No relationship between basal levels or levels after exposure to acrolein and CI could be identified. This implicates a minor role of inflammatory mediators on the systemic level in CI. Copyright © 2017 Elsevier Ltd. All rights reserved.

The adsorption of acrolein on a Pt (1 1 1): A study of chemical bonding and electronic structure

International Nuclear Information System (INIS)

Pirillo, S.; López-Corral, I.; Germán, E.; Juan, A.

2012-01-01

Highlights: ► Study of acrolein/Pt (1 1 1) adsorption using ab-initio and semiempirical methods. ► Geometry optimization and DOS curves were carried out using VASP code. ► Study of chemical bonding evolution using COOP and OP analysis. ► After adsorption Pt-Pt, C=O and C=C bonds are weakened. ► η 3 -cis and η 4 -trans most stable adsorption modes, η 1 -trans less favored one. - Abstract: The adsorption of acrolein on a Pt (1 1 1) surface was studied using ab-initio and semiempirical calculations. Geometry optimization and densities of states (DOS) curves were carried out using the Vienna Ab-initio Simulation Package (VASP) code. We started our study with the preferential geometries corresponding to the different acrolein/Pt (1 1 1) adsorption modes previously reported. Then, we examined the evolution of the chemical bonding in these geometries, using the crystal orbital overlap population (COOP) and overlap population (OP) analysis of selected pairs of atoms. We analyzed the acrolein intramolecular bonds, Pt (1 1 1) superficial bonds and new molecule-surface formed bonds after adsorption. We found that Pt-Pt bonds interacting with the molecule and acrolein C=O and C=C bonds are weakened after adsorption; this last bond is significantly linked to the surface. The obtained C-Pt and O-Pt OP values suggest that the most stable adsorption modes are η 3 -cis and η 4 -trans, while the η 1 -trans is the less favored configuration. We also found that C p z orbital and Pt p z and d z 2 orbitals participate strongly in the adsorption process.

Use of In Vivo and In Vitro Data to Derive a Chronic Reference Value for Crotonaldehyde Based on Relative Potency to Acrolein.

Science.gov (United States)

Grant, Roberta L; Jenkins, Allison F

2015-01-01

The Texas Commission on Environmental Quality (TCEQ) conducted a chronic inhalation noncancer toxicity assessment for crotonaldehyde (CRO). Since there were limited toxicity data for CRO, a reference value (ReV) was derived using a relative potency factor (RPF) approach with acrolein as the index chemical. Both CRO and acrolein are α,β-unsaturated carbonyls and share common steps in their mode of action (MOA). Only studies that investigated the effects of CRO and acrolein in the same study were used to calculate a CRO:acrolein RPF. In vivo findings measuring both 50% respiratory depression in rats and two species of mice and subcutaneous 50% lethality in rats and mice were used to calculate an RPF of 3 (rounded to one significant figure). In vitro data were useful to compare the MOA of CRO and acrolein and to support the RPF determined using in vivo data. In vitro cell culture studies investigating cytotoxicity in normal human lung fibroblast cultures using the propidium iodide cytotoxicity assay and in mouse lymphocyte cultures using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay were used to calculate an in vitro RPF of 3, which supports the in vivo RPF. The chronic ReV for acrolein of 1.2 ppb derived by TCEQ was multiplied by the RPF of 3 to calculate the ReV for CRO of 3.6 ppb (10 μg/m(3)). The ReV for CRO was developed to protect the general public from adverse health effects from chronic exposure to CRO in ambient air.

Lowest triplet (n, π*) electronic state of acrolein: Determination of structural parameters by cavity ringdown spectroscopy and quantum-chemical methods

Science.gov (United States)

Hlavacek, Nikolaus C.; McAnally, Michael O.; Drucker, Stephen

2013-02-01

The cavity ringdown absorption spectrum of acrolein (propenal, CH2=CH—CH=O) was recorded near 412 nm, under bulk-gas conditions at room temperature and in a free-jet expansion. The measured spectral region includes the 0^0_0 band of the T1(n, π*) ← S0 system. We analyzed the 0^0_0 rotational contour by using the STROTA computer program [R. H. Judge et al., J. Chem. Phys. 103, 5343 (1995)], 10.1063/1.470569, which incorporates an asymmetric rotor Hamiltonian for simulating and fitting singlet-triplet spectra. We used the program to fit T1(n, π*) inertial constants to the room-temperature contour. The determined values (cm-1), with 2σ confidence intervals, are A = 1.662 ± 0.003, B = 0.1485 ± 0.0006, C = 0.1363 ± 0.0004. Linewidth analysis of the jet-cooled spectrum yielded a value of 14 ± 2 ps for the lifetime of isolated acrolein molecules in the T1(n, π*), v = 0 state. We discuss the observed lifetime in the context of previous computational work on acrolein photochemistry. The spectroscopically derived inertial constants for the T1(n, π*) state were used to benchmark a variety of computational methods. One focus was on complete active space methods, such as complete active space self-consistent field (CASSCF) and second-order perturbation theory with a CASSCF reference function (CASPT2), which are applicable to excited states. We also examined the equation-of-motion coupled-cluster and time-dependent density function theory excited-state methods, and finally unrestricted ground-state techniques, including unrestricted density functional theory and unrestricted coupled-cluster theory with single and double and perturbative triple excitations. For each of the above methods, we or others [O. S. Bokareva et al., Int. J. Quantum Chem. 108, 2719 (2008)], 10.1002/qua.21803 used a triple zeta-quality basis set to optimize the T1(n, π*) geometry of acrolein. We find that the multiconfigurational methods provide the best agreement with fitted inertial

Sensory irritation to mixtures of formaldehyde, acrolein, and acetaldehyde in rats

NARCIS (Netherlands)

Cassee, F.R.; Arts, J.H.E.; Groten, J.P.; Feron, V.J.

1996-01-01

Sensory irritation of formaldehyde (FRM), acrolein (ACR) and acetaldehyde (ACE) as measured by the decrease in breathing frequency (DBF) was studied in male Wistar rats using nose-only exposure. Groups of four rats were exposed to each of the single compounds separately or to mixtures of FRM, ACR

Evaluation of N-acetylcysteine and methylprednisolone as therapies for oxygen and acrolein-induced lung damage

Energy Technology Data Exchange (ETDEWEB)

Critchley, J.A.J.H. (Univ. of Edinburgh (England)); Beeley, J.M.; Clark, R.J.; Buchanan, J.D. (Royal Naval Hospital Hoslar, Gosport (England)); Summerfield, M.; Bell, S. (Admiralty Research Establishment, Alverstoke (England)); Spurlock, M.S.; Edginton, J.A.G. (Chemical Defence Establishment, Porton Down (England))

1990-04-01

Reactive oxidizing species are implicated in the etiology of a range of inhalational pulmonary injuries. Consequently, various free radical scavengers have been tested as potential prophylactic agents. The sulfydryl compound, N-acetylcysteine (NAC) is the only such compound clinically available for use in realistic dosages, and it is well established as an effective antidote for the hepatic and renal toxicity of paracetamol. Another approach in pulmonary injury prophylaxis is methylprednisolone therapy. The authors evaluated NAC and methylprednisolone in two rats models of inhalation injury: 40-hr exposure to >97% oxygen at 1.1 bar and 15-min exposure to acrolein vapor (210 ppm). The increases in lung wet/dry weight ratios, seen with both oxygen and acrolein toxicity were reduced with both treatments. However, with oxygen, NAC therapy was associated with considerably increased mortality and histological changes. Furthermore, IP NAC administration resulted in large volumes of ascitic fluid. With acrolein, IV, NAC had no significant effect on mortality or pulmonary histological damage. Methylprednisolone had no beneficial effects on either the mortality or histological damage observed in either toxicity model. They caution against the ad hoc use of NAC in the management of inhalational pulmonary injury.

Acrolein-Induced Oxidative Stress and Cell Death Exhibiting Features of Apoptosis in the Yeast Saccharomyces cerevisiae Deficient in SOD1.

Science.gov (United States)

Kwolek-Mirek, Magdalena; Zadrąg-Tęcza, Renata; Bednarska, Sabina; Bartosz, Grzegorz

2015-04-01

The yeast Saccharomyces cerevisiae is a useful eukaryotic model to study the toxicity of acrolein, an important environmental toxin and endogenous product of lipid peroxidation. The study was aimed at elucidation of the cytotoxic effect of acrolein on the yeast deficient in SOD1, Cu, Zn-superoxide dismutase which is hypersensitive to aldehydes. Acrolein generated within the cell from its precursor allyl alcohol caused growth arrest and cell death of the yeast cells. The growth inhibition involved an increase in production of reactive oxygen species and high level of protein carbonylation. DNA condensation and fragmentation, exposition of phosphatidylserine at the cell surface as well as decreased dynamic of actin microfilaments and mitochondria disintegration point to the induction of apoptotic-type cell death besides necrotic cell death.

Cytotoxicity of Thirdhand Smoke and Identification of Acrolein as a Volatile Thirdhand Smoke Chemical That Inhibits Cell Proliferation.

Science.gov (United States)

Bahl, Vasundhra; Weng, Nikki J-H; Schick, Suzaynn F; Sleiman, Mohamad; Whitehead, Jacklyn; Ibarra, Allison; Talbot, Prue

2016-03-01

Thirdhand smoke (THS) is a mixture of chemicals that remain on indoor surfaces after smoking has ceased. These chemicals can be inhaled, ingested, or absorbed dermally, and thus could impact human health. We evaluated the cytotoxicity and mode of action of fresh and aged THS, the toxicity of volatile organic chemicals (VOCs) in THS, and the molecular targets of acrolein, a VOC in THS. Experiments were done using mouse neural stem cells (mNSC), human pulmonary fibroblasts (hPF), and lung A549 epithelial cells. THS-exposed cotton cloth was extracted in Dulbecco's Eagle Medium and caused cytotoxicity in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. THS extracts induced blebbing, immotility, vacuolization, cell fragmentation, severing of microfilaments and depolymerization of microtubules in mNSC. Cytotoxicity was inversely related to headspace volume in the extraction container and was lost upon aging, suggesting that VOCs in THS were cytotoxic. Phenol, 2',5'-dimethyl furan and acrolein were identified as the most cytotoxic VOCs in THS, and in combination, their cytotoxicity increased. Acrolein inhibited proliferation of mNSC and hPF and altered expression of cell cycle regulatory genes. Twenty-four hours of treatment with acrolein decreased expression of transcription factor Dp-1, a factor needed for the G1 to S transition in the cell cycle. At 48 h, WEE1 expression increased, while ANACP1 expression decreased consistent with blocking entry into and completion of the M phase of the cell cycle. This study identified acrolein as a highly cytotoxic VOC in THS which killed cells at high doses and inhibited cell proliferation at low doses. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Studies on the polymerization of acrolein oxime, 13

International Nuclear Information System (INIS)

Ota, Tadatoshi; Mori, Yoshikazu; Tamai, Harumi; Masuda, Seizo; Tanaka, Masami.

1980-01-01

The radiation-induced polymerization of acrolein oxime was carried out at temperatures ranging from room temperature to -78 0 C, and the resulting low molecular products were analyzed by gas chromatography-mass spectrometry. Acetaldoxime, propionaldoxime, propenylhydroxylamines, dioximes etc. were obtained. Initial processes of the polymerization are discussed on the basis of these reaction products. The present work offers further corroborating evidence for the already-described postulation that an anionic mechanism is operative above room temperature, and a cationic mechanism is predominant below -23 0 C. (author)

NMR investigation of acrolein stability in hydroalcoholic solution as a foundation for the valid HS-SPME/GC-MS quantification of the unsaturated aldehyde in beverages.

Science.gov (United States)

Kächele, Martin; Monakhova, Yulia B; Kuballa, Thomas; Lachenmeier, Dirk W

2014-04-11

Acrolein (propenal) is found in many foods and beverages and may pose a health hazard due to its cytotoxicity. Considerable knowledge gaps regarding human exposure to acrolein exist, and there is a lack of reliable analytical methods. Hydroalcoholic dilutions prepared for calibration purposes from pure acrolein show considerable degradation of the compound and nuclear magnetic resonance (NMR) spectroscopy showed that 1,3,3-propanetriol and 3-hydroxypropionaldehyde are formed. The degradation can be prevented by addition of hydroquinone as stabilizer to the calibration solutions, which then show linear concentration-response behaviour required for quantitative analysis. The stabilized calibration solutions were used for quantitative headspace solid-phase microextraction/gas chromatography-mass spectrometry (HS-SPME/GC-MS) determination of acrolein in alcoholic beverages with a detection limit of 14 μg L(-1). Of 117 tested alcoholic beverages, 64 were tested positive with the highest incidence in grape marc spirits and whiskey (100%, mean 252 μg L(-1)), followed by fruit spirits (86%, mean 591 μg/L(-1)), tequila (86%, mean 404 μg L(-1)), Asian spirits (43%, mean 54 μg L(-1)) and wine (9%, mean 0.7 μg L(-1)). Acrolein could not be detected in beer, vodka, absinthe and bottled water. Six of the fruit and grape marc spirits had acrolein levels above the World Health Organization (WHO) provisional tolerable concentration of 1.5 mg L(-1). Copyright © 2014 Elsevier B.V. All rights reserved.

Nanofilter platform based on functionalized carbon nanotubes for adsorption and elimination of Acrolein, a toxicant in cigarette smoke

Science.gov (United States)

Yoosefian, Mehdi; Pakpour, Atef; Etminan, Nazanin

2018-06-01

This paper discusses the use of carboxylated single-walled carbon nanotube as a general nanofilter platform for the removal of acrolein carcinogen from cigarette smoke. The analyses carried out in the detailed study of the electronic and structural effects of the adsorption of acrolein onto COOH loaded on single-walled carbon nanotube under the density functional theory framework. The results of Bader theory of atoms in molecules, natural bond orbital, molecular potential electron surface and density of state confirm the potential application of the suggested nanofilter platform.

Decarbonylation and hydrogenation reactions of allyl alcohol and acrolein on Pd(110)

Science.gov (United States)

Shekhar, Ratna; Barteau, Mark A.

1994-11-01

Allyl alcohol and acrolein reactions on the Pd(110) surface were investigated using temperature programmed desorption. For both unsaturated oxygenates, three coverage-dependent reaction pathways were observed. At low coverages, allyl alcohol decomposed completely to CO, hydrogen and carbonaceous species on the surface. For θ > 0.15 monolayer, ethylene (and small amounts of ethane) desorbed at ca. 295 K. Near saturation coverages, desorption of propanal was detected at ca. 235 K. The parent molecule, allyl alcohol, desorbed only after exposures sufficient to saturate these channels. Acrolein decomposition spectra were similar to those observed for allyl alcohol decomposition on the clean surface. Additional experiments with allyl alcohol on hydrogen- and deuterium-precoveredPd(110) surfaces demonstrated increased hydrogenation of the C 2-hydrocarbon products along with hydrogenation of allyl alcohol to 1-propanol. However, in contrast to previous results for allyl alcohol on the Pd(111) surface, there was no evidence for C-O scission reactions of any C 3 oxygenate on Pd(110).

Selective oxidation of propylene to acrolein by silica-supported bismuth molybdate catalysts

DEFF Research Database (Denmark)

Duc, Duc Truong; Ha, Hanh Nguyen; Fehrmann, Rasmus

2011-01-01

Silica-supported bismuth molybdate catalysts have been prepared by impregnation, structurally characterized and examined as improved catalysts for the selective oxidation of propylene to acrolein. Catalysts with a wide range of loadings (from 10 to 90 wt%) of beta bismuth molybdate (β-Bi2Mo2O9) w...

Toxicity of formaldehyde and acrolein mixtures : in vitro studies using nasal epithelial cells

NARCIS (Netherlands)

Cassee, F.R.; Stenhuis, W.S.; Groten, J.P.; Feron, V.J.

1996-01-01

In vitro studies with human and rat nasal epithelial cells were carried out to investigate the combined toxicity of formaldehyde and acrolein and the role of aldehyde dehydrogenases in this process. These studies showed that the toxic effect of mixtures of aldehydes was additive. In addition,

Detection of acrolein and acrylonitrile with a pulsed room temperature quantum cascade laser

Science.gov (United States)

Manne, J.; Jäger, W.; Tulip, J.

2010-06-01

We investigated the use of a pulsed, distributed feedback quantum cascade laser centered at 957 cm-1 in combination with an astigmatic Herriot cell with 250 m path length for the detection of acrolein and acrylonitrile. These molecules have been identified as hazardous air-pollutants because of their adverse health effects. The spectrometer utilizes the intra-pulse method, where a linear frequency down-chirp, that is induced when a top-hat current pulse is applied to the laser, is used for sweeping across the absorption line. Up to 450 ns long pulses were used for these measurements which resulted in a spectral window of ~2.2 cm-1. A room temperature mercury-cadmium-telluride detector was used, resulting in a completely cryogen free spectrometer. We demonstrated detection limits of ~3 ppb for acrylonitrile and ~6 ppb for acrolein with ~10 s averaging time. Laser characterization and optimization of the operational parameters for sensitivity improvement are discussed.

Sustainable Production of o-Xylene from Biomass-Derived Pinacol and Acrolein.

Science.gov (United States)

Hu, Yancheng; Li, Ning; Li, Guangyi; Wang, Aiqin; Cong, Yu; Wang, Xiaodong; Zhang, Tao

2017-07-21

o-Xylene (OX) is a large-volume commodity chemical that is conventionally produced from fossil fuels. In this study, an efficient and sustainable two-step route is used to produce OX from biomass-derived pinacol and acrolein. In the first step, the phosphotungstic acid (HPW)-catalyzed pinacol dehydration in 1-ethyl-3-methylimidazolium chloride ([emim]Cl) selectively affords 2,3-dimethylbutadiene. The high selectivity of this reaction can be ascribed to the H-bonding interaction between Cl - and the hydroxy group of pinacol. The stabilization of the carbocation intermediate by the surrounding anion Cl - may be another reason for the high selectivity. Notably, the good reusability of the HPW/[emim]Cl system can reduce the waste output and production cost. In the second step, OX is selectively produced by a Diels-Alder reaction of 2,3-dimethylbutadiene and acrolein, followed by a Pd/C-catalyzed decarbonylation/aromatization cascade in a one-pot fashion. The sustainable two-step process efficiently produces renewable OX in 79 % overall yield. Analogously, biomass-derived crotonaldehyde and pinacol can also serve as the feedstocks for the production of 1,2,4-trimethylbenzene. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effects of the prescription of reinforcing kidney, nourishing blood, improving eyesight on ARPE-19 cells induced by acrolein

Directory of Open Access Journals (Sweden)

Man Li

2015-05-01

Full Text Available AIM: To explore the effects of the prescription of reinforcing kidney, nourishing blood, improving eyesight on the oxidative stress model of ARPE-19 cells induced by acrolein. METHODS: SD rats serum containing the prescription of reinforcing kidney, nourishing blood, improving eyesight and the content of distilled water in serum were prepared. The effects of the prescription and distilled water in serum at different concentration(2.5%, 5%, 10%, 20% and 40%on cell vitality was observed by cell counting kit(CCK-8assay. the logarithmic phase of ARPE-19 cells were pretreated by different concentrations(1.25%, 2.5% and 5%of the prescription serum and distilled water in serum for 24h. Then it was treated with 75μmol/L acrolein for 24h. Cell vitality was observed by CCK-8 assay. The change of cell nucleus was detected by DAPI staining.RESULTS: 2.5% and 5% serum had no effect on cell viability(P>0.05, while 10%, 20%, 40% serum could inhibit cell viability(PPCONCLUSION: The prescription of reinforcing kidney, nourishing blood, improving eyesight has the protective effect on ARPE-19 cell damage induced by acrolein.

New Insights in the Pathogenesis of Multiple Sclerosis—Role of Acrolein in Neuronal and Myelin Damage

Directory of Open Access Journals (Sweden)

Riyi Shi

2013-10-01

Full Text Available Multiple sclerosis (MS is an autoimmune disease of the central nervous system (CNS characterized by an inappropriate inflammatory reaction resulting in widespread myelin injury along white matter tracts. Neurological impairment as a result of the disease can be attributed to immune-mediated injury to myelin, axons and mitochondria, but the molecular mechanisms underlying the neuropathy remain incompletely understood. Incomplete mechanistic knowledge hinders the development of therapies capable of alleviating symptoms and slowing disease progression in the long-term. Recently, oxidative stress has been implicated as a key component of neural tissue damage prompting investigation of reactive oxygen species (ROS scavengers as a potential therapeutic option. Despite the establishment of oxidative stress as a crucial process in MS development and progression, ROS scavengers have had limited success in animal studies which has prompted pursuit of an alternative target capable of curtailing oxidative stress. Acrolein, a toxic β-unsaturated aldehyde capable of initiating and perpetuating oxidative stress, has been suggested as a viable point of intervention to guide the development of new treatments. Sequestering acrolein using an FDA-approved compound, hydralazine, offers neuroprotection resulting in dampened symptom severity and slowed disease progression in experimental autoimmune encephalomyelitis (EAE mice. These results provide promise for therapeutic development, indicating the possible utility of neutralizing acrolein to preserve and improve neurological function in MS patients.

Selective Production of Toluene from Biomass-Derived Isoprene and Acrolein.

Science.gov (United States)

Dai, Tao; Li, Changzhi; Zhang, Bo; Guo, Haiwei; Pan, Xiaoli; Li, Lin; Wang, Aiqin; Zhang, Tao

2016-12-20

Toluene is a basic chemical that is currently produced from petroleum resources. In this paper, we report a new route for the effective synthesis of toluene from isoprene and acrolein, two reactants readily available from biomass, through a simple two-step reaction. The process includes Diels-Alder cycloaddition of isoprene and acrolein in a Zn-containing ionic liquid at room temperature to produce methylcyclohex-3-enecarbaldehydes (MCHCAs) as intermediates, followed by M (M=Pt, Pd, Rh)/Al 2 O 3 -catalyzed consecutive dehydrogenation-decarbonylation of the MCHCAs at 573 K to generate toluene with an overall yield up to 90.7 %. Model reactions indicated that a synergistic inductive effect of the C=C double bond and the aldehyde group in MCHCA plays a key role in initiating the consecutive dehydrogenation-decarbonylation, and that methyl benzaldehydes are the key intermediates in the gas-phase transformation of MCHCAs. Microcalorimetric adsorption of CO on different catalysts showed that decarbonylation of the substrate occurs more likely on the strong adsorption sites. To the best of our knowledge, it is the first report of Pt/Al 2 O 3 -catalyzed consecutive dehydrogenation-decarbonylation of a given compound in one reactor. This work provides a highly efficient and environmental friendly route to toluene by utilizing two compounds that can be prepared from biomass. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Acrolein Exposure in Hookah Smokers and Non-Smokers Exposed to Hookah Tobacco Secondhand Smoke: Implications for Regulating Hookah Tobacco Products.

Science.gov (United States)

Kassem, Nada O F; Kassem, Noura O; Liles, Sandy; Zarth, Adam T; Jackson, Sheila R; Daffa, Reem M; Chatfield, Dale A; Carmella, Steven G; Hecht, Stephen S; Hovell, Melbourne F

2018-03-06

Acrolein is a highly ciliatoxic agent, a toxic respiratory irritant, a cardiotoxicant, and a possible carcinogen present in tobacco smoke including hookah tobacco. 105 hookah smokers and 103 non-smokers attended exclusively hookah smoking social events at either a hookah lounge or private home, and provided urine samples the morning of and the morning after the event. Samples were analyzed for 3-hydroxypropylmercapturic acid (3-HPMA), a metabolite of acrolein. Geometric mean (GM) urinary 3-HPMA levels in hookah smokers and non-smokers exposed to secondhand smoke (SHS) increased significantly, 1.41 times, 95% CI = 1.15 to 1.74 and 1.39 times, 95% CI = 1.16 to 1.67, respectively, following a hookah social event. The highest increase (1.68 times, 95% CI = 1.15 to 2.45; p = 0.007) in 3-HPMA post a hookah social event was among daily hookah smokers (GM, from 1991 pmol/mg to 3348 pmol/mg). Pre-to-post event change in urinary 3-HPMA was significantly positively correlated with pre-to-post event change in urinary cotinine among hookah smokers at either location of hookah event, (ρ = 0.359, p = 0.001), and among non-smokers in hookah lounges (ρ = 0.369, p = 0.012). Hookah tobacco smoke is a source of acrolein exposure. Findings support regulating hookah tobacco products including reducing humectants and sugar additives, which are precursors of acrolein under certain pyrolysis conditions. We suggest posting health warning signs for indoor smoking in hookah lounges, and encouraging voluntary bans of smoking hookah tobacco in private homes. Our study is the first to quantify the increase in acrolein exposure in hookah smokers and non-smokers exposed to exclusively hookah tobacco SHS at hookah social events in homes or hookah lounges. Our findings provide additional support for regulating hookah tobacco product content, protecting non-smokers' health by posting health warning signs for indoor smoking in hookah lounges, and encouraging home bans on hookah tobacco smoking to

Sensitive detection of acrolein and acrylonitrile with a pulsed quantum-cascade laser

Science.gov (United States)

Manne, J.; Lim, A.; Tulip, J.; Jäger, W.

2012-05-01

We report on spectroscopic measurements of acrolein and acrylonitrile at atmospheric pressure using a pulsed distributed feedback quantum-cascade laser in combination with intra- and inter-pulse techniques and compare the results. The measurements were done in the frequency region around 957 cm-1. In the inter-pulse technique, the laser is excited with short current pulses (5-10 ns), and the pulse amplitude is modulated with an external current ramp resulting in a ˜2.3 cm-1 frequency scan. In the intra-pulse technique, a linear frequency down-chirp during the pulse is used for sweeping across the absorption line. Long current pulses up to 500 ns were used for these measurements which resulted in a spectral window of ˜2.2 cm-1 during the down-chirp. These comparatively wide spectral windows facilitated the measurements of the relatively broad absorption lines (˜1 cm-1) of acrolein and acrylonitrile. The use of a room-temperature mercury-cadmium-telluride detector resulted in a completely cryogen-free spectrometer. We demonstrate ppb level detection limits within a data acquisition time of ˜10 s with these methodologies.

A Comparative Study of Basic, Amphoteric, and Acidic Catalysts in the Oxidative Coupling of Methanol and Ethanol for Acrolein Production.

Science.gov (United States)

Lilić, Aleksandra; Wei, Tiantian; Bennici, Simona; Devaux, Jean-François; Dubois, Jean-Luc; Auroux, Aline

2017-09-11

The impact of acid/base properties (determined by adsorption microcalorimetry) of various catalysts on the cross-aldolization of acetaldehyde and formaldehyde leading to acrolein was methodically studied in oxidizing conditions starting from a mixture of methanol and ethanol. The aldol condensation and further dehydration to acrolein were carried out on catalysts presenting various acid/base properties (MgO, Mg-Al oxides, Mg/SiO 2 , NbP, and heteropolyanions on silica, HPA/SiO 2 ). Thermodynamic calculations revealed that cross-aldolization is always favored compared with self-aldolization of acetaldehyde, which leads to crotonaldehyde formation. The presence of strong basic sites is shown to be necessary, but a too high amount drastically increases CO x production. On strong acid sites, production of acrolein and carbon oxides (CO x ) does not increase with temperature. The optimal catalyst for this process should be amphoteric with a balanced acid/base cooperation of medium strength sites and a small amount (150 kJ mol -1 ). © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Field experiences using acrolein (2-propenal) for control of SRB and MIC in an offshore production flowline and onshore production facility in Western Australia

Energy Technology Data Exchange (ETDEWEB)

Shield, M.; Charlesworth, M.; Paakkonen, S.

2006-03-15

Acrolein, 2-propenal, was evaluated as a microbiocide for control of sulphate-reducing bacteria (SRB) in a sub-sea pipeline and an onshore process plant operated by ChevronTexaco Australia Pty Ltd (CVX) in the North West Shelf (NWS) of Australia. An initial trial compared the efficacy of acrolein with that of a glutaraldehyde, quaternary amine blend (GQB) for control of SRB implicated in microbiologically induced corrosion (MIC) of the sub-sea pipeline. Based on improved performance, acrolein subsequently replaced the GQB for routine microbiocide treatment of the pipeline. In addition, a plant trial assessed the impact of acrolein supplementation of the existing tetrakishydroxy-methyl phosphonium sulphate (THPS) microbiocide programme for control of SRB in process plant operations. This paper overviews both the pipeline and plant trials as well as the programme implementation of acrolein microbiocide for routine pipeline treatment. In addition to an improved performance and safety profile, complete conversion of the microbiocide programme to acrolein is projected to result in direct savings of 40%, with further potential for secondary operational cost savings. on behalf of Ampol and Caltex; and, in 1964, the company discovered oil in commercial quantities on Barrow Island (BWI) off the North West Shelf of Australia. Today, CVX continues hydrocarbon production operations on BWI with over 300 million barrels produced since inception. BWI volumes have been augmented since 1989 through hydrocarbon recovery operations near Thevenard Island (TVI), a small island located 25 km north-north west of Onslow. To date, more than 146 million barrels have been processed through facilities on TVI. With the process plant covering only a small corner of the island, the majority of land mass on TVI is classified as a nature reserve for the protection of plants and animals. Important wildlife found on the island include green and flatback turtles that nest on the islands beaches. In

A comparative study of the adsorption and hydrogenation of acrolein on Pt(1 1 1), Ni(1 1 1) film and Pt Ni Pt(1 1 1) bimetallic surfaces

Science.gov (United States)

Murillo, Luis E.; Chen, Jingguang G.

In this study we have investigated the reaction pathways for the decomposition and hydrogenation of acrolein (CH 2dbnd CH-CH dbnd O) on Ni/Pt(1 1 1) surfaces under ultra-high vacuum (UHV) conditions using temperature programmed desorption (TPD) and high-resolution electron energy loss spectroscopy (HREELS). While gas-phase hydrogenation products are not observed from clean Pt(1 1 1), the subsurface Pt-Ni-Pt(1 1 1), with Ni residing below the first layer of Pt, is active for the self-hydrogenation of the C dbnd O bond to produce unsaturated alcohol (2-propenol) and the C dbnd C bond to produce saturated aldehyde (propanal), with the latter being the main hydrogenation product without the consecutive hydrogenation to saturated alcohol. For a thick Ni(1 1 1) film prepared on Pt(1 1 1), the self-hydrogenation yields for both products are lower than that from the Pt-Ni-Pt(1 1 1) surface. The presence of pre-adsorbed hydrogen further enhances the selectivity toward C dbnd O bond hydrogenation on the Pt-Ni-Pt(1 1 1) surface. In addition, HREELS studies of the adsorption of the two hydrogenation products, 2-propenol and propanal, are performed on the Pt-Ni-Pt(1 1 1) surface to identify the possible surface intermediates during the reaction of acrolein. The results presented here indicate that the hydrogenation activity and selectivity of acrolein on Pt(1 1 1) can be significantly modified by the formation of the bimetallic surfaces.

Electronic excitations in a dielectric continuum solvent with quantum Monte Carlo: Acrolein in water

NARCIS (Netherlands)

Floris, F.M.; Filippi, Claudia; Amovilli, C.

2014-01-01

We investigate here the vertical n → π* and π → π* transitions of s-trans-acrolein in aqueous solution by means of a polarizable continuum model (PCM) we have developed for the treatment of the solute at the quantum Monte Carlo (QMC) level of the theory. We employ the QMC approach which allows us to

甘油脱水制丙烯醛催化剂的研究进展%Research progress in glycerol dehydration to acrolein

Institute of Scientific and Technical Information of China (English)

黄士学; 崔洪友; 钱绍松; 谷俊峰; 卜小蒙

2012-01-01

With the increasing of biodiesel production,a large volume of byproduct glycerol has led to a market surplus.Dehydration of glycerol to acrolein is considered to be an efficient and effective route to improve the economic efficiency of biodiesel production.The reaction characteristics of glycerol dehydration to acrolein under the liquid phase,gas phase and sub-/supercritical water conditions are analyzed.The emphasis is given to the catalysts for glycerol dehydration in gas phase.Effects of microstructure,acidity of the active phase and redox site on the catalytic activity,selectivity and longevity are discussed.The causes for catalyst deactivation are also involved.Moreover,the reaction mechanisms of glycerol dehydration proposed in the literature are presented and the research work in glycerol dehydration to acrolein in the future is proposed.%伴随着生物柴油的产量不断增大,大量副产的甘油导致了市场过剩。甘油脱水制取丙烯醛是提高生物柴油经济性的一条有效途径。本文结合近年来甘油脱水制丙烯醛的研究进展情况,分析了液相、气相以及超（亚）临界条件下该反应的特点,重点阐述了气相脱水催化剂的研究进展,讨论了催化剂的微观结构、活性组分的酸碱性和氧化还原位等对催化剂活性、选择性和寿命等的影响,分析了催化剂失活的原因。此外,还讨论了甘油脱水过程的反应机理,指出了今后甘油脱水制丙烯醛的研究方向。

Simultaneous exposure to concentrated ambient particles and acrolein causes cardiac effects mediated by parasympathetic modulation in mice

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This study shows that exposure to CAPs and acrolein causes an increase in HRV that is mediated by the parasympathetic nervous system. Numerous studies show that short-term air pollution exposure modulates heart rate variability (HRV), which is an indicator of autonomic influence...

Acrolein Causes TRPA1-Mediated Sensory Irritation and Indirect Potentiation of TRPV1-Mediated Pulmonary Chemoreflex Response

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We previously demonstrated that acute exposure to acrolein causes immediate sensory irritation, with rapid decrease in heart rate (HR) and increase in inspiratory time (Ti), and potentiation of pulmonary chemoreflex response 24hrs later; of these effects only the latter is mediat...

Changes in the nasal epithelium of rats exposed by inhalation to mixtures of formaldehyde, acetaldehyde, and acrolein

NARCIS (Netherlands)

Cassee, F.R.; Groten, J.P.; Feron, V.J.

1996-01-01

Formaldehyde, acetaldehyde, and acrolein are well-known upper respiratory tract irritants and occur simultaneously as pollutants in many indoor and outdoor environments. The upper respiratory tract, and especially the nose, is the prime target for inhaled aldehydes. To study possible additive or

Influenza A infection attenuates relaxation responses of mouse tracheal smooth muscle evoked by acrolein.

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Cheah, Esther Y; Mann, Tracy S; Burcham, Philip C; Henry, Peter J

2015-02-15

The airway epithelium is an important source of relaxant mediators, and damage to the epithelium caused by respiratory tract viruses may contribute to airway hyperreactivity. The aim of this study was to determine whether influenza A-induced epithelial damage would modulate relaxation responses evoked by acrolein, a toxic and prevalent component of smoke. Male BALB/c mice were inoculated intranasally with influenza A/PR-8/34 (VIRUS-infected) or allantoic fluid (SHAM-infected). On day 4 post-inoculation, isometric tension recording studies were conducted on carbachol pre-contracted tracheal segments isolated from VIRUS and SHAM mice. Relaxant responses to acrolein (30 μM) were markedly smaller in VIRUS segments compared to SHAM segments (2 ± 1% relaxation vs. 28 ± 5%, n=14, pacrolein and SP were reduced in VIRUS segments (>35% reduction, n=6, pacrolein were profoundly diminished in tracheal segments isolated from influenza A-infected mice. The mechanism through which influenza A infection attenuates this response appears to involve reduced production of PGE2 in response to SP due to epithelial cell loss, and may provide insight into the airway hyperreactivity observed with influenza A infection. Copyright © 2014 Elsevier Inc. All rights reserved.

Protective Effect of Silymarin against Acrolein-Induced Cardiotoxicity in Mice

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Elahe Taghiabadi

2012-01-01

Full Text Available Reactive α,β-unsaturated aldehydes such as acrolein (ACR are major components of environmental pollutants and have been implicated in the neurodegenerative and cardiac diseases. In this study, the protective effect of silymarin (SN against cardiotoxicity induced by ACR in mice was evaluated. Studies were performed on seven groups of six animals each, including vehicle-control (normal saline + 0.5% w/v methylcellulose, ACR (7.5 mg/kg/day, gavage for 3 weeks, SN (25, 50 and 100 mg/kg/day, i.p. plus ACR, vitamin E (Vit E, 100 IU/kg, i.p. plus ACR, and SN (100 mg/kg, i.p. groups. Mice received SN 7 days before ACR and daily thereafter throughout the study. Pretreatment with SN attenuated ACR-induced increased levels of malondialdehyde (MDA, serum cardiac troponin I (cTnI, and creatine kinase-MB (CK-MB, as well as histopathological changes in cardiac tissues. Moreover, SN improved glutathione (GSH content, superoxide dismutase (SOD, and catalase (CAT activities in heart of ACR-treated mice. Western blot analysis showed that SN pretreatment inhibited apoptosis provoked by ACR through decreasing Bax/Bcl-2 ratio, cytosolic cytochrome c content, and cleaved caspase-3 level in heart. In conclusion, SN may have protective effects against cardiotoxicity of ACR by reducing lipid peroxidation, renewing the activities of antioxidant enzymes, and preventing apoptosis.

Mercapturic Acids Derived from the Toxicants Acrolein and Crotonaldehyde in the Urine of Cigarette Smokers from Five Ethnic Groups with Differing Risks for Lung Cancer.

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Park, Sungshim L; Carmella, Steven G; Chen, Menglan; Patel, Yesha; Stram, Daniel O; Haiman, Christopher A; Le Marchand, Loic; Hecht, Stephen S

2015-01-01

The Multiethnic Cohort epidemiology study has clearly demonstrated that, compared to Whites and for the same number of cigarettes smoked, African Americans and Native Hawaiians have a higher risk for lung cancer whereas Latinos and Japanese Americans have a lower risk. Acrolein and crotonaldehyde are two important constituents of cigarette smoke which have well documented toxic effects and could play a role in lung cancer etiology. Their urinary metabolites 3-hydroxypropylmercapturic acid (3-HPMA) and 3-hydroxy-1-methylpropylmercapturic acid (HMPMA), respectively, are validated biomarkers of acrolein and crotonaldehyde exposure. We quantified levels of 3-HPMA and HMPMA in the urine of more than 2200 smokers from these five ethnic groups, and also carried out a genome wide association study using blood samples from these subjects. After adjusting for age, sex, creatinine, and total nicotine equivalents, geometric mean levels of 3-HPMA and HMPMA were significantly different in the five groups (P acrolein and crotonaldehyde may be involved in lung cancer etiology, and that their divergent levels may partially explain the differing risks of Native Hawaiian and Latino smokers. No strong signals were associated with 3-HPMA in the genome wide association study, suggesting that formation of the glutathione conjugate of acrolein is mainly non-enzymatic, while the top significant association with HMPMA was located on chromosome 12 near the TBX3 gene, but its relationship to HMPMA excretion is not clear.

Product Analysis of the {OH} Oxidation of Acrolein and Methacrolein in the Presence of {NO}

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Dransfield, T. J.; Sprengnether, M. M.; Huang, Y.; Donahue, N. M.; Demerjian, K. L.; Anderson, J. G.

2002-12-01

The oxidation of acrolein and methacrolein by OH in the presence of high NO was studied under "wall-less" conditions in Harvard's High Pressure Flow System. The experiment was conducted at 450 torr with a reaction time of several seconds. In the present work, first stage products are formed at 1013 molecules/cm3 levels and analyzed in-situ by FTIR spectroscopy. The use of Reaction Modulation Spectroscopy allows for accurate measurement of the very small(~1%) change in unsaturated aldehyde and NO reactants, in addition to product concentrations. Observed products from the acrolein oxidation include: formaldehyde(CH2O), glyoxal(CHOCHO), glycolaldehyde(CH2OHCHO), ketene(CH2CO), nitrogen dioxide, carbon dioxide and carbon monoxide. The methacrolein oxidation produces: formaldehyde, methylgyloxal(CH3COCHO), hydroxyacetone(CH2OHC(O)CH3), ketene, nitrogen dioxide, carbon dioxide and carbon monoxide. Both reactions also produce peroxynitrates and alkylnitrates that have proven difficult to spectrally resolve. We observe elevated yields of ketene relative to previously published experiments conducted on longer timescales. We interpret this as evidence of rapid ketene removal in these systems. The mechanisms for ketene formation are discussed.

Matrix metalloproteinase 2 (MMP-2) levels are increased in active acromegaly patients.

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Karci, Alper Cagri; Canturk, Zeynep; Tarkun, Ilhan; Cetinarslan, Berrin

2017-07-01

During follow-up of acromegaly patients, there is a discordance rate of 30% between the measurements of growth hormone and insulin-like growth factor-1 levels. Further tests are required to determine disease activity in patients with discordant results. This study was planned to investigate an association of serum levels of matrix metalloproteinase-2, matrix metalloproteinase-9, and cathepsin B with disease activity in acromegaly patients. In this study, 64 acromegaly patients followed in our clinic were divided into two groups according to the 2010 consensus criteria for cure of acromegaly as patients with active disease (n = 24) and patients with controlled disease (n = 40). Serum matrix metalloproteinase-2, matrix metalloproteinase-9, and cathepsin B levels were measured by the enzyme-linked immunosorbent assay method. The mean serum matrix metalloproteinase-2 level was significantly higher in the active acromegaly patients than in the controlled acromegaly patients (150.1 ± 54.5 ng/mL vs. 100.2 ± 44.6 ng/mL; p matrix metalloproteinase-9 and cathepsin B levels (p = 0.205 and p = 0.598, respectively). Serum matrix metalloproteinase-2 levels of 118.3 ng/mL and higher had a sensitivity of 75% and a specificity of 77.5% in determining active disease. The risk of active acromegaly was 3.3 fold higher in the patients with a matrix metalloproteinase-2 level of >118.3 ng/mL than in the patients with a matrix metalloproteinase-2 level of matrix metalloproteinase-2 level is increased in the active acromegaly patients and a threshold value in determining active disease was defined for serum matrix metalloproteinase-2 level. This study is the first to compare acromegaly patients having active or controlled disease in terms of matrix metalloproteinase-2 and matrix metalloproteinase-9 levels. The results need to be confirmed by a study that will be conducted in a larger patient group also including a healthy control group to demonstrate the

Effect of thermal treatment conditions on properties of vanadium molybdenum oxide catalyst in acrolein oxidation reaction to acrylic acid

International Nuclear Information System (INIS)

Gorshkova, T.P.; Tarasova, D.V.; Olen'kova, I.P.; Andrushkevich, T.V.; Nikoro, T.A.

1984-01-01

The effect of thermal treatment conditions (temperature and gas medium) on properties of vanadium molybdenum oxide catalyst in acrolein oxidation reaction to acrylic acid is investigated. It is shown that active and selective catalysts are formed in the course of thermal decomposition of the drying product of ammonium metavanadate and paramolybdate under the conditions ensuring the vanadium ion reduction up to tetravalent state with conservation of molybdenum oxidation degree equal to 6. It is possible to realize it either by treatment of the catalyst calcinated in the air flow at 300 deg by the reaction mixture at the activation stage or by gas-reducer flow treatment at 280 deg. Thermal treatment in the reducing medium of the oxidized catalyst does not lead to complete regeneration of its properties

The health- and addictive effectes due to exposure to aldehydes of cigarette smoke. Part 1; Acetaldehyde, Formaldehyde, Acrolein and Propionaldehyde

NARCIS (Netherlands)

van Andel I; Schenk E; Rambali B; Wolterink G; van de Werken G; Stevenson H; van Aerts LAGJM; Vleeming W; LEO; LGM; LOC; CRV

2003-01-01

In deze literatuurstudie worden de gezondheids- en mogelijke verslavende effecten van blootstelling aan aldehyden ten gevolge van het roken van sigaretten beschreven. Dit literatuuronderzoek richt zich met name op acetaldehyde, formaldehyde, acrolein, en propionaldehyde. Alle aldehyden veroorzaken

HPLC-MS Determination of Acrolein and Acetone Generated from 13C3 -Labeled Glycerol Added to Cigarette Tobacco Using Two Machine-Smoking Regimes

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Yip SH

2014-12-01

Full Text Available The extent of blend glycerol degradation in a burning cigarette to form acrolein and acetone has been quantitatively determined by the addition of glycerol-13C3 to three styles of a leading commercial cigarette brand. Multiple Cambridge pads soaked with a solution of 2,4-dinitrophenylhydrazine (DNPH were employed to trap hydrazone derivatives of low molecular weight carbonyl compounds in both mainstream and sidestream smoke. High performance liquid chromatography coupled with negative ion mass spectrometry was used to isolate DNPH derivatives of the volatile carbonyl products of combustion and to ascertain their concentration. Acrolein, acetone, and propionaldehyde were the principal compounds of interest. The DNPH derivatives of acrolein-13C3 and acetone-13C3 were independently synthesized, and they served as external standards for absolute quantitation. The cost of fully labeled propionaldehyde precluded its use in this study. The brand styles selected for study represent the cigarette design features that are most prevalent in the U.S. market today and afford a representative range of standardized “tar” yields (14, 10, and 5 mg/cig, respectively by the Cambridge Filter Method. The brand styles studied are part of a commercial cigarette brand family that does not contain additives to the tobacco blend, including glycerol. Mainstream smoke was generated by an automated smoking machine employing the standard Cambridge Filter Smoking Regime and a more intense regime requiring larger, more frequent puffs and 100% vent blocking that is specified for regulatory purposes by the Canadian federal government. The research indicated that only a small fraction of added glycerol (~0.25%-0.30%, w/w was converted to the two compounds of interest, with the larger portion generally observed in sidestream smoke. Less than 0.1% of the added glycerol was converted to acrolein in mainstream smoke for all cigarette designs and smoking regimes studied.

Structure and stability of acrolein and allyl alcohol networks on Ag(111) from density functional theory based calculations with dispersion corrections

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Ferullo, Ricardo M.; Branda, Maria Marta; Illas, Francesc

2013-11-01

The interaction of acrolein and allyl alcohol with the Ag(111) surface has been studied by means of periodic density functional theory based calculations including explicitly dispersion terms. Different coverage values have been explored going from isolated adsorbed molecules to isolated dimers, interacting dimers or ordered overlayers. The inclusion of the dispersion terms largely affects the calculated values of the adsorption energy and also the distance between adsorbed molecule and the metallic surface but much less the adsorbate-adsorbate interactions. Owing to the large dipole moment of acrolein, the present calculations predict that at high coverage this molecule forms a stable extensive two-dimensional network on the surface, caused by the alignment of the adsorbate dipoles. For the case of allyl alcohol, dimers and complex networks exhibit similar stability.

pH-Sensitive Microparticles with Matrix-Dispersed Active Agent

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Li, Wenyan (Inventor); Buhrow, Jerry W. (Inventor); Jolley, Scott T. (Inventor); Calle, Luz M. (Inventor)

2014-01-01

Methods to produce pH-sensitive microparticles that have an active agent dispersed in a polymer matrix have certain advantages over microcapsules with an active agent encapsulated in an interior compartment/core inside of a polymer wall. The current invention relates to pH-sensitive microparticles that have a corrosion-detecting or corrosion-inhibiting active agent or active agents dispersed within a polymer matrix of the microparticles. The pH-sensitive microparticles can be used in various coating compositions on metal objects for corrosion detecting and/or inhibiting.

Nanocarbons as catalyst for selective oxidation of acrolein to acrylic acid

Energy Technology Data Exchange (ETDEWEB)

Frank, B.; Blume, R.; Rinaldi, A.; Trunschke, A.; Schloegl, R. [Fritz Haber Institute of the Max Planck Society, Berlin (Germany). Dept. of Inorganic Chemistry

2011-07-01

Selective oxidations are key steps of industrial oil and gas processing for the synthesis of high-value chemicals. Mixed metal oxides based on redox active V or Mo are frequently used for oxidative C-H bond activation. However, multiple processes require precious metals or suffer from low product selectivity demanding an ongoing search for cost-effective alternatives. Recently, the nanostructured carbon was reported to catalyze the metal-free selective alkane activation by oxidative dehydrogenation (ODH). Electron-rich surface carbonyls coordinate this reaction and mimic the active oxygen species in metal oxide catalysts. Here we show that the graphitic carbon, beyond ODH, has the potential to selectively mediate the insertion of an oxygen atom into an organic molecule, i.e., acrolein. Multi-step atom rearrangements considerably exceed the mechanistic complexity of hydrogen abstraction and were so far believed to be the exclusive domain of metal (oxide) catalysis. In the carbon catalyzed process, the nucleophilic oxygen atoms terminating the graphite (0001) surface abstract the formyl hydrogen and the activated aldehyde gets oxidized by epoxide-type mobile oxygen, thus the sp{sup 2} carbon acts as a bifunctional catalyst. Substantial similarities between the metal oxide- and carbon-catalyzed reactions could be identified. Our results shed light on a rarely known facet of applications of nanostructured carbon materials being decorated with diverse oxygen functionalities to coordinate complex catalytic processes. We could successfully transfer the results obtained from the graphite model to carbon nanotubes (CNTs) providing a higher surface area, defect density, and intrinsic activity, to substantially increase the reactivity per catalyst volume. Indeed, low dimensional nanostructured carbon is a highly flexible and robust material which can be modified in a multiple manner to optimize its properties with respect to the intended application. The exploration of

Acrolein preferentially damages nucleolus eliciting ribosomal stress and apoptosis in human cancer cells.

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Wang, Hsiang-Tsui; Chen, Tzu-Ying; Weng, Ching-Wen; Yang, Chun-Hsiang; Tang, Moon-Shong

2016-12-06

Acrolein (Acr) is a potent cytotoxic and DNA damaging agent which is ubiquitous in the environment and abundant in tobacco smoke. Acr is also an active cytotoxic metabolite of the anti-cancer drugs cyclophosphamide and ifosfamide. The mechanisms via which Acr exerts its anti-cancer activity and cytotoxicity are not clear. In this study, we found that Acr induces cytotoxicity and cell death in human cancer cells with different activities of p53. Acr preferentially binds nucleolar ribosomal DNA (rDNA) to form Acr-deoxyguanosine adducts, and induces oxidative damage to both rDNA and ribosomal RNA (rRNA). Acr triggers ribosomal stress responses, inhibits rRNA synthesis, reduces RNA polymerase I binding to the promoter of rRNA gene, disrupts nucleolar integrity, and impairs ribosome biogenesis and polysome formation. Acr causes an increase in MDM2 levels and phosphorylation of MDM2 in A549 and HeLa cells which are p53 active and p53 inactive, respectively. It enhances the binding of ribosomal protein RPL11 to MDM2 and reduces the binding of p53 and E2F-1 to MDM2 resulting in stabilization/activation of p53 in A549 cells and degradation of E2F-1 in A549 and HeLa cells. We propose that Acr induces ribosomal stress which leads to activation of MDM2 and RPL11-MDM2 binding, consequently, activates p53 and enhances E2F-1 degradation, and that taken together these two processes induce apoptosis and cell death.

In parkinsonian substantia nigra, alpha-synuclein is modified by acrolein, a lipid-peroxidation product, and accumulates in the dopamine neurons with inhibition of proteasome activity.

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Shamoto-Nagai, M; Maruyama, W; Hashizume, Y; Yoshida, M; Osawa, T; Riederer, P; Naoi, M

2007-01-01

alpha-Synuclein (alphaSYN) plays a central role in the neural degeneration of Parkinson's disease (PD) through its conformational change. In PD, alphaSYN, released from the membrane, accumulates in the cytoplasm and forms Lewy body. However, the mechanism behind the translocation and conformational change of alphaSYN leading to the cell death has not been well elucidated. This paper reports that in the dopamine neurons of the substantia nigra containing neuromelanin from PD patients, alphaSYN was modified with acrolein (ACR), an aldehyde product of lipid peroxidation. Histopathological observation confirmed the co-localization of protein immunoreactive to anti-alphaSYN and ACR antibody. By Western blot analyses of samples precipitated with either anti-alphaSYN or anti-ACR antibody, increase in ACR-modified alphaSYN was confirmed in PD brain. Modification of recombinant alphaSYN by ACR enhanced its oligomerization, and at higher ACR concentrations alphaSYN was fragmented and polymerized forming a smear pattern in SDS-PAGE. ACR reduced 20S proteasome activity through the direct modification of the proteasome proteins and the production of polymerized ACR-modified proteins, which inhibited proteasome activity in vitro. These results suggest that ACR may initiate vicious cycle of modification and aggregation of proteins, including alphaSYN, and impaired proteolysis system, to cause neuronal death in PD.

Computational Approaches to the Determination of the Molecular Geometry of Acrolein in its T_1(n,π*) State

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McAnally, Michael O.; Hlavacek, Nikolaus C.; Drucker, Stephen

2012-06-01

The spectroscopically derived inertial constants for acrolein (propenal) in its T_1(n,π*) state were used to test predictions from a variety of computational methods. One focus was on multiconfigurational methods, such as CASSCF and CASPT2, that are applicable to excited states. We also examined excited-state methods that utilize single reference configurations, including EOM-EE-CCSD and TD-PBE0. Finally, we applied unrestricted ground-state techniques, such as UCCSD(T) and the more economical UPBE0 method, to the T_1(n,π*) excited state under the constraint of C_s symmetry. The unrestricted ground-state methods are applicable because at a planar geometry, the T_1(n,π*) state of acrolein is the lowest-energy state of its spin multiplicity. Each of the above methods was used with a triple zeta quality basis set to optimize the T_1(n,π*) geometry. This procedure resulted in the following sets of inertial constants: Inertial constants (cm-1) of acrolein in its T_1(n,π*) state Method A B C Method A B C CASPT2(6,5) 1.667 0.1491 0.1368 UCCSD(T)^b 1.668 0.1480 0.1360 CASSCF(6,5) 1.667 0.1491 0.1369 UPBE0 1.699 0.1487 0.1367 EOM-EE-CCSD 1.675 0.1507 0.1383 TD-PBE0 1.719 0.1493 0.1374 Experiment^a 1.662 0.1485 0.1363 The two multiconfigurational methods produce the same inertial constants, and those constants agree closely with experiment. However the sets of computed bond lengths differ significantly for the two methods. In the CASSCF calculation, the lengthening of the C=O and C=C bonds and the shortening of the C--C bond are more pronounced than in CASPT2. O. S. Bokareva et al., Int. J. Quant. Chem. {108}, 2719 (2008).

Calcium-Oxidant Signaling Network Regulates AMP-activated Protein Kinase (AMPK) Activation upon Matrix Deprivation*

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Sundararaman, Ananthalakshmy; Amirtham, Usha; Rangarajan, Annapoorni

2016-01-01

The AMP-activated protein kinase (AMPK) has recently been implicated in anoikis resistance. However, the molecular mechanisms that activate AMPK upon matrix detachment remain unexplored. In this study, we show that AMPK activation is a rapid and sustained phenomenon upon matrix deprivation, whereas re-attachment to the matrix leads to its dephosphorylation and inactivation. Because matrix detachment leads to loss of integrin signaling, we investigated whether integrin signaling negatively regulates AMPK activation. However, modulation of focal adhesion kinase or Src, the major downstream components of integrin signaling, failed to cause a corresponding change in AMPK signaling. Further investigations revealed that the upstream AMPK kinases liver kinase B1 (LKB1) and Ca2+/calmodulin-dependent protein kinase kinase β (CaMKKβ) contribute to AMPK activation upon detachment. In LKB1-deficient cells, we found AMPK activation to be predominantly dependent on CaMKKβ. We observed no change in ATP levels under detached conditions at early time points suggesting that rapid AMPK activation upon detachment was not triggered by energy stress. We demonstrate that matrix deprivation leads to a spike in intracellular calcium as well as oxidant signaling, and both these intracellular messengers contribute to rapid AMPK activation upon detachment. We further show that endoplasmic reticulum calcium release-induced store-operated calcium entry contributes to intracellular calcium increase, leading to reactive oxygen species production, and AMPK activation. We additionally show that the LKB1/CaMKK-AMPK axis and intracellular calcium levels play a critical role in anchorage-independent cancer sphere formation. Thus, the Ca2+/reactive oxygen species-triggered LKB1/CaMKK-AMPK signaling cascade may provide a quick, adaptable switch to promote survival of metastasizing cancer cells. PMID:27226623

Mercapturic Acids Derived from the Toxicants Acrolein and Crotonaldehyde in the Urine of Cigarette Smokers from Five Ethnic Groups with Differing Risks for Lung Cancer.

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Sungshim L Park

Full Text Available The Multiethnic Cohort epidemiology study has clearly demonstrated that, compared to Whites and for the same number of cigarettes smoked, African Americans and Native Hawaiians have a higher risk for lung cancer whereas Latinos and Japanese Americans have a lower risk. Acrolein and crotonaldehyde are two important constituents of cigarette smoke which have well documented toxic effects and could play a role in lung cancer etiology. Their urinary metabolites 3-hydroxypropylmercapturic acid (3-HPMA and 3-hydroxy-1-methylpropylmercapturic acid (HMPMA, respectively, are validated biomarkers of acrolein and crotonaldehyde exposure. We quantified levels of 3-HPMA and HMPMA in the urine of more than 2200 smokers from these five ethnic groups, and also carried out a genome wide association study using blood samples from these subjects. After adjusting for age, sex, creatinine, and total nicotine equivalents, geometric mean levels of 3-HPMA and HMPMA were significantly different in the five groups (P < 0.0001. Native Hawaiians had the highest and Latinos the lowest geometric mean levels of both 3-HPMA and HMPMA. Levels of 3-HPMA and HMPMA were 3787 and 2759 pmol/ml urine, respectively, in Native Hawaiians and 1720 and 2210 pmol/ml urine in Latinos. These results suggest that acrolein and crotonaldehyde may be involved in lung cancer etiology, and that their divergent levels may partially explain the differing risks of Native Hawaiian and Latino smokers. No strong signals were associated with 3-HPMA in the genome wide association study, suggesting that formation of the glutathione conjugate of acrolein is mainly non-enzymatic, while the top significant association with HMPMA was located on chromosome 12 near the TBX3 gene, but its relationship to HMPMA excretion is not clear.

Towards the sustainable production of acrolein by glycerol dehydration.

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Katryniok, Benjamin; Paul, Sébastien; Capron, Mickaël; Dumeignil, Franck

2009-01-01

The massive increase in biodiesel production by transesterification of vegatable oils goes hand-in-hand with the availability of a large volume of glycerol, which must be valorized. Glycerol dehydration to acrolein over acid catalysts is one of the most promising ways of valorization, because this compound is an important chemical intermediate used in, for example, the DL-methionine synthesis. In this Minireview, we give a detailed critical view of the state-of-the-art of this dehydration reaction. The processes developed in both the liquid and the gas phases are detailed and the best catalytic results obtained so far are reported as a benchmark for future developments. The advances on the understanding of the reaction mechanism are also discussed and we further focus particularly on the main obstacles for an immediate industrial application of this technology, namely catalyst coking and crude glycerol direct-use issues.

Theoretical Study on Regioselectivity of the Diels-Alder Reaction between 1,8-Dichloroanthracene and Acrolein.

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Sultan, Mujeeb A; Karama, Usama; Almansour, Abdulrahman I; Soliman, Saied M

2016-09-23

A theoretical study of the regioselectivity of the Diels-Alder reaction between 1,8-dichloroanthracene and acrolein is performed using DFT at the B3LYP/6-31G(d,p) level of theory. The FMO analysis, global and local reactivity indices confirmed the reported experimental results. Potential energy surface analysis showed that the cycloadditions (CAs) favor the formation of the anti product. These results are in good agreement with the reported results obtained experimentally where the anti is the major product.

Transient receptor potential cation channel A1 (TRPA1) mediates changes in heart rate variability following a single exposure to acrolein in mice

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The data show that a single exposure to acrolein causes autonomic imbalance in mice through the TRPA1 sensor and subsequent cardiac dysfunction. Human and animal studies have shown that short-term air pollution exposure causes...

Influence of environmental parameters on production of the acrolein precursor 3-hydroxypropionaldehyde by Lactobacillus reuteri DSMZ 20016 and its accumulation by wine lactobacilli.

Science.gov (United States)

Bauer, Rolene; du Toit, Maret; Kossmann, Jens

2010-01-31

Lactic acid bacteria belonging to the genus Lactobacillus are known to convert glycerol into 3-hydroxypropionaldehyde (3-HPA) during anaerobic glycerol fermentation. Wine quality can be gravely compromised by the accumulation of 3-HPA, due to its spontaneous conversion to acrolein under wine making conditions. Acrolein is not only a dangerous substance for the living cell, but has been implicated in the development of unpleasant bitterness in beverages. This study evaluates the effect of individual environmental parameters on 3-HPA production by Lactobacillus reuteri DSMZ 20016, which only proved possible under conditions that allow accumulation well below the threshold concentration affecting cell viability. 3-HPA production was optimal at pH 6 and in the presence of 300 mM glycerol. Production increased with an increase in cell concentration up to an OD(600) of 50, whereas higher cell concentrations inhibited accumulation. Data presented in this study suggest that 3-HPA plays a role in regulating its own production through quorum sensing. Glycerol dehydratase possessing bacterial strains isolated from South African red wine, L. pentosus and L. brevis, tested positive for 3-HPA accumulation. 3-HPA is normally intracellularly reduced to 1,3-propanediol. This is the first study demonstrating the ability of wine lactobacilli to accumulate 3-HPA in the fermentation media. Recommendations are made on preventing the formation of acrolein and its precursor 3-HPA in wine. Copyright 2009 Elsevier B.V. All rights reserved.

Theoretical Study on Regioselectivity of the Diels-Alder Reaction between 1,8-Dichloroanthracene and Acrolein

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Mujeeb A. Sultan

2016-09-01

Full Text Available A theoretical study of the regioselectivity of the Diels-Alder reaction between 1,8-dichloroanthracene and acrolein is performed using DFT at the B3LYP/6-31G(d,p level of theory. The FMO analysis, global and local reactivity indices confirmed the reported experimental results. Potential energy surface analysis showed that the cycloadditions (CAs favor the formation of the anti product. These results are in good agreement with the reported results obtained experimentally where the anti is the major product.

'Real-world' compensatory behaviour with low nicotine concentration e-liquid: subjective effects and nicotine, acrolein and formaldehyde exposure.

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Dawkins, Lynne; Cox, Sharon; Goniewicz, Maciej; McRobbie, Hayden; Kimber, Catherine; Doig, Mira; Kośmider, Leon

2018-06-07

To compare the effects of i) high versus low nicotine concentration e-liquid, ii) fixed versus adjustable power and iii) the interaction between the two on: a) vaping behaviour, b) subjective effects, c) nicotine intake, and d) exposure to acrolein and formaldehyde in e-cigarette users vaping in their everyday setting. Counterbalanced, repeated measures with four conditions: i) low nicotine (6 mg/mL)/fixed power; ii) low nicotine/adjustable power; iii) high nicotine (18 mg/mL)/fixed power; iv) high nicotine/adjustable power. London and the South East, England. Twenty experienced e-cigarette users (recruited between September 2016 and February 2017) vaped ad libitum using an eVic Supreme™ with a 'Nautilus Aspire' tank over four weeks (one week per condition). Puffing patterns (daily puff number [PN], puff duration [PD], inter-puff interval [IPI]), mL of e-liquid consumed, changes to power (where permitted), and subjective effects (urge to vape, nicotine withdrawal symptoms) were measured in each condition. Nicotine intake was measured via salivary cotinine. 3-hydroxypropylmercapturic acid (3-HPMA), a metabolite of the toxicant acrolein, and formate, a metabolite of the carcinogen formaldehyde, were measured in urine. There was a significant nicotine concentration x power interaction for PD (p<0.01). PD was longer with low nicotine/fixed power compared with i) high nicotine/fixed power (p< 0.001 and ii) low nicotine/adjustable power (p< 0.01). PN and liquid consumed were higher in the low versus high nicotine condition (main effect of nicotine, p<0.05). Urge to vape and withdrawal symptoms were lower, and nicotine intake was higher, in the high nicotine condition (main effects of nicotine: p<0.01). Whilst acrolein levels did not differ, there was a significant nicotine x power interaction for formaldehyde (p<0.05). Use of a lower nicotine concentration e-liquid may be associated with compensatory behaviour (e.g., higher number and duration of puffs) and increases

Cooperative properties of single phases of complex oxide catalyst for oxidation of propylene to acrolein

International Nuclear Information System (INIS)

Orel, L.I.; Udalova, O.V.; Korchak, V.N.; Isaev, O.V.; Krylov, O.V.; Gershenzon, Yu.M.; Aptekar', E.L.

1992-01-01

Synergetic effect of increase of acrolein yield during propylene oxidation on mechanical mixture of (α + β)CoMoO 4 and MoO 3 , as well as CO and CO 2 yield on mixture of CoMoO 4 and Bi 2 O 3 ·2MoO 3 was revealed. It is shown that CoMoO 4 generates allyl radicals, desorption of these radicals to gaseous phase is not practically observed with MoO 3 , bismuth molybdates and Fe 2 O 3 · Fe 2 O 3 ·3MoO 3

Google matrix of the world network of economic activities

Science.gov (United States)

Kandiah, Vivek; Escaith, Hubert; Shepelyansky, Dima L.

2015-07-01

Using the new data from the OECD-WTO world network of economic activities we construct the Google matrix G of this directed network and perform its detailed analysis. The network contains 58 countries and 37 activity sectors for years 1995 and 2008. The construction of G, based on Markov chain transitions, treats all countries on equal democratic grounds while the contribution of activity sectors is proportional to their exchange monetary volume. The Google matrix analysis allows to obtain reliable ranking of countries and activity sectors and to determine the sensitivity of CheiRank-PageRank commercial balance of countries in respect to price variations and labor cost in various countries. We demonstrate that the developed approach takes into account multiplicity of network links with economy interactions between countries and activity sectors thus being more efficient compared to the usual export-import analysis. The spectrum and eigenstates of G are also analyzed being related to specific activity communities of countries.

Inhibition of acrolein-induced autophagy and apoptosis by a glycosaminoglycan from Sepia esculenta ink in mouse Leydig cells.

Science.gov (United States)

Gu, Yi-Peng; Yang, Xiao-Mei; Luo, Ping; Li, Yan-Qun; Tao, Ye-Xing; Duan, Zhen-Hua; Xiao, Wei; Zhang, Da-Yan; Liu, Hua-Zhong

2017-05-01

In our recent reports, a squid ink polysaccharide (SIP) was found having preventive activity against cyclophosphamide induced damage in mouse testis and ovary. Here we further reveal the regulative mechanism of SIP against chemical toxicity on testis. Leydig cells exposed to acrolein (ACR) underwent apoptosis at 12h and 24h. Before apoptosis, cells occurred autophagy that was confirmed by high autophagic rate and Beclin-1 protein content at 3h. PI3K/Akt and p38 MAPK signal pathways involved in the regulatory mechanisms. These outcomes of ACR were recovered completely by SIP, which was demonstrated by attenuated disruption of redox equilibrium and increased testosterone production, through suppressing ACR-caused autophagy and apoptosis regulated by PI3K/Akt and p38 MAPK signal pathways in Leydig cells. Summarily, autophagy occurred before apoptosis caused by ACR-activated p38 MAPK and PI3K/Akt pathways were blocked by SIP, resulting in survival and functional maintenance of Leydig cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

Matrix metalloproteinase activity assays: Importance of zymography.

Science.gov (United States)

Kupai, K; Szucs, G; Cseh, S; Hajdu, I; Csonka, C; Csont, T; Ferdinandy, P

2010-01-01

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases capable of degrading extracellular matrix, including the basement membrane. MMPs are associated with various physiological processes such as morphogenesis, angiogenesis, and tissue repair. Moreover, due to the novel non-matrix related intra- and extracellular targets of MMPs, dysregulation of MMP activity has been implicated in a number of acute and chronic pathological processes, such as arthritis, acute myocardial infarction, chronic heart failure, chronic obstructive pulmonary disease, inflammation, and cancer metastasis. MMPs are considered as viable drug targets in the therapy of the above diseases. For the development of selective MMP inhibitor molecules, reliable methods are necessary for target validation and lead development. Here, we discuss the major methods used for MMP assays, focusing on substrate zymography. We highlight some problems frequently encountered during sample preparations, electrophoresis, and data analysis of zymograms. Zymography is a widely used technique to study extracellular matrix-degrading enzymes, such as MMPs, from tissue extracts, cell cultures, serum or urine. This simple and sensitive technique identifies MMPs by the degradation of their substrate and by their molecular weight and therefore helps to understand the widespread role of MMPs in different pathologies and cellular pathways. Copyright 2010 Elsevier Inc. All rights reserved.

Electronic excitations in a dielectric continuum solvent with quantum Monte Carlo: Acrolein in water

International Nuclear Information System (INIS)

Floris, Franca Maria; Amovilli, Claudio; Filippi, Claudia

2014-01-01

We investigate here the vertical n → π * and π → π * transitions of s-trans-acrolein in aqueous solution by means of a polarizable continuum model (PCM) we have developed for the treatment of the solute at the quantum Monte Carlo (QMC) level of the theory. We employ the QMC approach which allows us to work with highly correlated electronic wave functions for both the solute ground and excited states and, to study the vertical transitions in the solvent, adopt the commonly used scheme of considering fast and slow dielectric polarization. To perform calculations in a non-equilibrium solvation regime for the solute excited state, we add a correction to the global dielectric polarization charge density, obtained self consistently with the solute ground-state wave function by assuming a linear-response scheme. For the solvent polarization in the field of the solute in the ground state, we use the static dielectric constant while, for the electronic dielectric polarization, we employ the solvent refractive index evaluated at the same frequency of the photon absorbed by the solute for the transition. This choice is shown to be better than adopting the most commonly used value of refractive index measured in the region of visible radiation. Our QMC calculations show that, for standard cavities, the solvatochromic shifts obtained with the PCM are underestimated, even though of the correct sign, for both transitions of acrolein in water. Only by reducing the size of the cavity to values where more than one electron is escaped to the solvent region, we regain the experimental shift for the n → π * case and also improve considerably the shift for the π → π * transition

Electronic excitations in a dielectric continuum solvent with quantum Monte Carlo: Acrolein in water

Science.gov (United States)

Floris, Franca Maria; Filippi, Claudia; Amovilli, Claudio

2014-01-01

We investigate here the vertical n → π* and π → π* transitions of s-trans-acrolein in aqueous solution by means of a polarizable continuum model (PCM) we have developed for the treatment of the solute at the quantum Monte Carlo (QMC) level of the theory. We employ the QMC approach which allows us to work with highly correlated electronic wave functions for both the solute ground and excited states and, to study the vertical transitions in the solvent, adopt the commonly used scheme of considering fast and slow dielectric polarization. To perform calculations in a non-equilibrium solvation regime for the solute excited state, we add a correction to the global dielectric polarization charge density, obtained self consistently with the solute ground-state wave function by assuming a linear-response scheme. For the solvent polarization in the field of the solute in the ground state, we use the static dielectric constant while, for the electronic dielectric polarization, we employ the solvent refractive index evaluated at the same frequency of the photon absorbed by the solute for the transition. This choice is shown to be better than adopting the most commonly used value of refractive index measured in the region of visible radiation. Our QMC calculations show that, for standard cavities, the solvatochromic shifts obtained with the PCM are underestimated, even though of the correct sign, for both transitions of acrolein in water. Only by reducing the size of the cavity to values where more than one electron is escaped to the solvent region, we regain the experimental shift for the n → π* case and also improve considerably the shift for the π → π* transition.

New intracellular activities of matrix metalloproteinases shine in the moonlight.

Science.gov (United States)

Jobin, Parker G; Butler, Georgina S; Overall, Christopher M

2017-11-01

Adaption of a single protein to perform multiple independent functions facilitates functional plasticity of the proteome allowing a limited number of protein-coding genes to perform a multitude of cellular processes. Multifunctionality is achievable by post-translational modifications and by modulating subcellular localization. Matrix metalloproteinases (MMPs), classically viewed as degraders of the extracellular matrix (ECM) responsible for matrix protein turnover, are more recently recognized as regulators of a range of extracellular bioactive molecules including chemokines, cytokines, and their binders. However, growing evidence has convincingly identified select MMPs in intracellular compartments with unexpected physiological and pathological roles. Intracellular MMPs have both proteolytic and non-proteolytic functions, including signal transduction and transcription factor activity thereby challenging their traditional designation as extracellular proteases. This review highlights current knowledge of subcellular location and activity of these "moonlighting" MMPs. Intracellular roles herald a new era of MMP research, rejuvenating interest in targeting these proteases in therapeutic strategies. This article is part of a Special Issue entitled: Matrix Metalloproteinases edited by Rafael Fridman. Copyright © 2017 Elsevier B.V. All rights reserved.

DFT-Based Explanation of the Effect of Simple Anionic Ligands on the Regioselectivity of the Heck Arylation of Acrolein Acetals

DEFF Research Database (Denmark)

Henriksen, Signe Teuber; Tanner, David Ackland; Cacchi, Sandro

2009-01-01

The Heck arylation of acrolein acetal has been studied computationally and compared to the corresponding reaction with allyl ethers. The reaction can be controlled to give either cinnamaldehydes or arylpropanoic esters by addition of different coordinating anions, acetate, or chloride. The comput...... reaction conditions. The difference between the two substrate classes could be rationalized in terms of relative hydride donating power of the two substrates....

Comparative analysis of the vibrational structure of the absorption spectra of acrolein in the excited ( S 1) electronic state

Science.gov (United States)

Koroleva, L. A.; Tyulin, V. I.; Matveev, V. K.; Pentin, Yu. A.

2012-04-01

The assignments of absorption bands of the vibrational structure of the UV spectrum are compared with the assignments of bands obtained by the CRDS method in a supersonic jet from the time of laser radiation damping for the trans isomer of acrolein in the excited ( S 1) electronic state. The ν00 trans = 25861 cm-1 values and fundamental frequencies, including torsional vibration frequency, obtained by the two methods were found to coincide in the excited electronic state ( S 1) for this isomer. The assignments of several absorption bands of the vibrational structure of the spectrum obtained by the CRDS method were changed. Changes in the assignment of (0-v') transition bands of the torsional vibration of the trans isomer in the Deslandres table from the ν00 trans trans origin allowed the table to be extended to high quantum numbers v'. The torsional vibration frequencies up to v' = 5 were found to be close to the frequencies found by analyzing the vibrational structure of the UV spectrum and calculated quantum-mechanically. The coincidence of the barrier to internal rotation (the cis-trans transition) in the one-dimensional model with that calculated quantum-mechanically using the two-dimensional model corresponds to a planar structure of the acrolein molecule in the excited ( S 1) electronic state.

Kinematic matrix theory and universalities in self-propellers and active swimmers.

Science.gov (United States)

Nourhani, Amir; Lammert, Paul E; Borhan, Ali; Crespi, Vincent H

2014-06-01

We describe an efficient and parsimonious matrix-based theory for studying the ensemble behavior of self-propellers and active swimmers, such as nanomotors or motile bacteria, that are typically studied by differential-equation-based Langevin or Fokker-Planck formalisms. The kinematic effects for elementary processes of motion are incorporated into a matrix, called the "kinematrix," from which we immediately obtain correlators and the mean and variance of angular and position variables (and thus effective diffusivity) by simple matrix algebra. The kinematrix formalism enables us recast the behaviors of a diverse range of self-propellers into a unified form, revealing universalities in their ensemble behavior in terms of new emergent time scales. Active fluctuations and hydrodynamic interactions can be expressed as an additive composition of separate self-propellers.

Electronic excitations in a dielectric continuum solvent with quantum Monte Carlo: Acrolein in water

Energy Technology Data Exchange (ETDEWEB)

Floris, Franca Maria, E-mail: floris@dcci.unipi.it; Amovilli, Claudio [Dipartimento di Chimica e Chimica Industriale, Università di Pisa, Via Risorgimento 35, 56126 Pisa (Italy); Filippi, Claudia [MESA Institute for Nanotechnology, University of Twente, P.O. Box 217, 7500 AE Enschede (Netherlands)

2014-01-21

We investigate here the vertical n → π{sup *} and π → π{sup *} transitions of s-trans-acrolein in aqueous solution by means of a polarizable continuum model (PCM) we have developed for the treatment of the solute at the quantum Monte Carlo (QMC) level of the theory. We employ the QMC approach which allows us to work with highly correlated electronic wave functions for both the solute ground and excited states and, to study the vertical transitions in the solvent, adopt the commonly used scheme of considering fast and slow dielectric polarization. To perform calculations in a non-equilibrium solvation regime for the solute excited state, we add a correction to the global dielectric polarization charge density, obtained self consistently with the solute ground-state wave function by assuming a linear-response scheme. For the solvent polarization in the field of the solute in the ground state, we use the static dielectric constant while, for the electronic dielectric polarization, we employ the solvent refractive index evaluated at the same frequency of the photon absorbed by the solute for the transition. This choice is shown to be better than adopting the most commonly used value of refractive index measured in the region of visible radiation. Our QMC calculations show that, for standard cavities, the solvatochromic shifts obtained with the PCM are underestimated, even though of the correct sign, for both transitions of acrolein in water. Only by reducing the size of the cavity to values where more than one electron is escaped to the solvent region, we regain the experimental shift for the n → π{sup *} case and also improve considerably the shift for the π → π{sup *} transition.

SPARC regulates extracellular matrix organization through its modulation of integrin-linked kinase activity.

Science.gov (United States)

Barker, Thomas H; Baneyx, Gretchen; Cardó-Vila, Marina; Workman, Gail A; Weaver, Matt; Menon, Priya M; Dedhar, Shoukat; Rempel, Sandra A; Arap, Wadih; Pasqualini, Renata; Vogel, Viola; Sage, E Helene

2005-10-28

SPARC, a 32-kDa matricellular glycoprotein, mediates interactions between cells and their extracellular matrix, and targeted deletion of Sparc results in compromised extracellular matrix in mice. Fibronectin matrix provides provisional tissue scaffolding during development and wound healing and is essential for the stabilization of mature extracellular matrix. Herein, we report that SPARC expression does not significantly affect fibronectin-induced cell spreading but enhances fibronectin-induced stress fiber formation and cell-mediated partial unfolding of fibronectin molecules, an essential process in fibronectin matrix assembly. By phage display, we identify integrin-linked kinase as a potential binding partner of SPARC and verify the interaction by co-immunoprecipitation and colocalization in vitro. Cells lacking SPARC exhibit diminished fibronectin-induced integrin-linked kinase activation and integrin-linked kinase-dependent cell-contractile signaling. Furthermore, induced expression of SPARC in SPARC-null fibroblasts restores fibronectin-induced integrin-linked kinase activation, downstream signaling, and fibronectin unfolding. These data further confirm the function of SPARC in extracellular matrix organization and identify a novel mechanism by which SPARC regulates extracellular matrix assembly.

The mild liquid-phase synthesis of 3-picoline from acrolein diethyl acetal and ammonia over heterogeneous catalysts

Science.gov (United States)

Luo, Cai-Wu; Chao, Zi-Sheng; Lei, Bo; Wang, Hong; Zhang, Jun; Wang, Zheng-Hao

2017-11-01

The liquid-phase synthesis of 3-picoline from the reaction of acrolein diethyl acetal and ammonia over ion-exchanged resins (D402 and D002) and HZSM-5 (Si/Al = 25) was carried out in a batch reactor. Various influencing parameters, including by the addition of water, ion-exchanged resins, reaction temperature and HZSM-5, were systematically investigated. The results showed that the reaction could be directly conducted, and organic acid wasn’t utilized. The highest yield of 3-picoline reached up to 24% using HZSM-5 as catalyst at 110 °C.

ASTM and VAMAS activities in titanium matrix composites test methods development

Science.gov (United States)

Johnson, W. S.; Harmon, D. M.; Bartolotta, P. A.; Russ, S. M.

1994-01-01

Titanium matrix composites (TMC's) are being considered for a number of aerospace applications ranging from high performance engine components to airframe structures in areas that require high stiffness to weight ratios at temperatures up to 400 C. TMC's exhibit unique mechanical behavior due to fiber-matrix interface failures, matrix cracks bridged by fibers, thermo-viscoplastic behavior of the matrix at elevated temperatures, and the development of significant thermal residual stresses in the composite due to fabrication. Standard testing methodology must be developed to reflect the uniqueness of this type of material systems. The purpose of this paper is to review the current activities in ASTM and Versailles Project on Advanced Materials and Standards (VAMAS) that are directed toward the development of standard test methodology for titanium matrix composites.

Thermotolerant cyclamen with reduced acrolein and methyl vinyl ketone.

Science.gov (United States)

Kai, Hiroomi; Hirashima, Keita; Matsuda, Osamu; Ikegami, Hidetoshi; Winkelmann, Traud; Nakahara, Takao; Iba, Koh

2012-06-01

Reduced levels of trienoic fatty acids (TAs) in chloroplast membranes induce thermotolerance in several plant species, but the underlying mechanisms remain unclear. TA peroxidation in plant cell membranes generates cytotoxic, TA-derived compounds containing α,β-unsaturated carbonyl groups. The relationship between low TA levels and the amounts of cytotoxic TA-derived compounds was examined using thermotolerant transgenic cyclamen (Cyclamen persicum Mill.) with low TA contents. Changes in the levels of the cytotoxic TA-derived acrolein (ACR), methyl vinyl ketone (MVK), (E)-2-hexenal, 4-hydroxy-2-nonenal, and malondialdehyde were analysed in the leaf tissues of wild-type (WT) and thermotolerant transgenic cyclamen under heat stress. Levels of ACR and MVK in the WT increased in parallel with the occurrence of heat-induced tissue damage, whereas no such changes were observed in the thermotolerant transgenic lines. Furthermore, exogenous ACR and MVK infiltrated into leaves to concentrations similar to those observed in heat-stressed WT leaves caused similar disease symptoms. These results suggest that thermotolerance in transgenic cyclamen depends on reduced production rates of ACR and MVK under heat stress, due to the low level of TAs in these plants.

Activity of matrix metalloproteinases during antimycobacterial therapy in mice with simulated tuberculous inflammation.

Science.gov (United States)

Sumenkova, D V; Russkikh, G S; Poteryaeva, O N; Polyakov, L M; Panin, L E

2013-05-01

Matrix metalloproteinases are shown to be involved in the pathogenesis of tuberculosis inflammation. In the early stages of BCG-granuloma formation in mouse liver and lungs, the serum levels of matrix metalloproteinases 2 and 7 increased by 4.5 times and remained unchanged while the pathology developed. Antimycobacterial therapy with isoniazid reduced enzyme activity almost to the level of intact control. The decrease in activity of matrix metalloproteinases 2 and 7 that play the most prominent role in the development of destructive forms of tuberculosis is of great therapeutic importance.

Immobilization of mercury and zinc in an alkali-activated slag matrix.

Science.gov (United States)

Qian, Guangren; Sun, Darren Delai; Tay, Joo Hwa

2003-07-04

The behavior of heavy metals mercury and zinc immobilized in an alkali-activated slag (AAS) matrix has been evaluated using physical property tests, pore structure analysis and XRD, TG-DTG, FTIR and TCLP analysis. Low concentrations (0.5%) of mercury and zinc ions had only a slight affect on compressive strength, pore structure and hydration of AAS matrixes. The addition of 2% Hg ions to the AAS matrix resulted in a reduction in early compressive strength but no negative effects were noticed after 28 days of hydration. Meanwhile, 2% Hg ions can be effectively immobilized in the AAS matrix with the leachate meeting the USEPA TCLP mercury limit. For a 2% Zn-doped AAS matrix, the hydration of the AAS paste was greatly retarded and the zinc concentration in the leachate from this matrix was higher than 5mg/l even at 28 days. Based on these results, we conclude that the physical encapsulation and chemical fixation mechanisms were likely to be responsible for the immobilization of Hg ions in the AAS matrix while only chemical fixation mechanisms were responsible for the immobilization of Zn ions in the AAS matrix.

A hands-on activity for teaching product-process matrix: roadmap and application

Directory of Open Access Journals (Sweden)

Luciano Costa Santos

2014-08-01

Full Text Available The product-process matrix is a well-known framework proposed by Hayes and Wheelwright (1979 that is commonly used to identify processes types and to analyze the alignment of these processes with the products of a company. For didactic purposes, the matrix helps undergraduates beginners from Production Engineering to understand the logic of production systems, providing knowledge that will be essential for various course subjects. Considering the high level of abstraction of the concepts underlying the product-process matrix, this paper presents a way to facilitate the learning of them through the application of a hands-on activity which relies on the active learning philosophy. The proposed dynamic uses colored plastic sheets and PVC pipes as main materials, differing from the original proposal of Penlesky and Treleven (2005 . In addition to presenting an extremely simple exercise, which encourages its application in the classroom, another contribution of this paper is to define a complete roadmap for conducting the activity. This roadmap describes the assembly of fictitious products in customization and standardization scenarios for the comparison of two processes types of product-process matrix, job shop and assembly line. The activity revealed very successful after its application to two groups of Production Engineering undergraduates, confirmed with positive feedback from the students surveyed.

Matrix metalloproteinases with gelatinolytic activity induced by Paracoccidioides brasiliensis infection

Science.gov (United States)

Nishikaku, Angela Satie; Ribeiro, Luciana Cristina; Molina, Raphael Fagnani Sanchez; Albe, Bernardo Paulo; Cunha, Cláudia da Silva; Burger, Eva

2009-01-01

Matrix metalloproteinases (MMPs) modulate extracellular matrix turnover, inflammation and immunity. We studied MMP-9 and MMP-2 in experimental paracoccidioidomycosis. At 15 and 120 days after infection (DAI) with virulent Paracoccidioides brasiliensis, MMP-9 was positive by immunohistochemistry in multinucleated giant cells, in mononuclear cells with macrophage and lymphocyte morphologies and also in fungal cells in the lesions of susceptible and resistant mice. Using gelatin zymography, pro- and active MMP-9 and active MMP-2 were detected in all infected mice, but not in controls. Gelatinolytic activity was not observed in P. brasiliensis extracts. Semiquantitative analysis of gelatinolytic activities revealed weak or absent MMP-2 and strong MMP-9 activity in both mouse strains at 15 DAI, declining at 120 DAI. Avirulent P. brasiliensis-infected mice had residual lesions with MMP-9-positive pseudoxantomatous macrophages, but no gelatinase activity at 120 DAI. Our findings demonstrate the induction of MMPs, particularly MMP-9, in experimental paracoccidioidomycosis, suggesting a possible influence in the pattern of granulomas and in fungal dissemination. PMID:19765107

Acrolein Exposure Blocks Down-Regulation of Cytokines and IgE Antibody in a Mucosal Tolerance Model but does not Alter Phenotypic Markers of Allergic Lung Disease

Science.gov (United States)

Acrolein (ACR) is a highly reactive upper airway toxicant that humans are exposed in a variety of environmental situations. Here we examined the effect of ACR exposure on development of immune tolerance in mice. To induce tolerance, female BALB/C mice were intranasally inoculate...

Approximate inclusion of triple excitations in combined coupled cluster/molecular mechanics: Calculations of electronic excitation energies in solution for acrolein, water, formamide, and n-methylacetamide

DEFF Research Database (Denmark)

Sneskov, Kristian; Gras, Eduard Matito; Kongsted, Jacob

2010-01-01

as being applicable for averaging over many solvent configurations derived from, for example, molecular simulations. We test the proposed model using as a benchmark the two lowest-lying valence singlet excitations (n → π* and π → π*) of acrolein, formamide, and N-methylacetamide in aqueous solution as well...

Study of ternary-component bismuth molybdate catalysts by 18O2 tracer in the oxidation of propylene to acrolein

International Nuclear Information System (INIS)

Ueda, W.; Moro-oka, Y.; Ikawa, T.

1981-01-01

Participation of lattice oxide ions of ternary-component bismuth molybdate catalysts M-Bi-Mo-O (M = Ni, Co, Mg, Mn, Ca, Sr, Ba, and Pb) was investigated using the 18 O 2 tracer in the selective oxidation of propylene to acrolein. The participation of the lattice oxide ions in the oxidation is prominent on every catalyst but the extent of the participation varies significantly depending on the structure of the catalyst. Only lattice oxide ions in the bismuth molybdate phase are incorporated into the oxidized products on the catalysts (M = Ni, Co, Mg, and Mn) where M have smaller ionic radius than Bi 3+ ; catalyst particles are composed of a shell of bismuth molybdates and a core of MMoO 4 . On the other hand, whole oxide ions in the active particles are involved in the oxidation on catalysts having a scheelite-type structure (M = Ca, Sr, Ba, and Pb) where M has a comparable ionic radius to Bi 3+

Superoxide activates mitochondrial uncoupling protein 2 from the matrix side. Studies using targeted antioxidants.

Science.gov (United States)

Echtay, Karim S; Murphy, Michael P; Smith, Robin A J; Talbot, Darren A; Brand, Martin D

2002-12-06

Superoxide activates nucleotide-sensitive mitochondrial proton transport through the uncoupling proteins UCP1, UCP2, and UCP3 (Echtay, K. S., et al. (2002) Nature 415, 1482-1486). Two possible mechanisms were proposed: direct activation of the UCP proton transport mechanism by superoxide or its products and a cycle of hydroperoxyl radical entry coupled to UCP-catalyzed superoxide anion export. Here we provide evidence for the first mechanism and show that superoxide activates UCP2 in rat kidney mitochondria from the matrix side of the mitochondrial inner membrane: (i) Exogenous superoxide inhibited matrix aconitase, showing that external superoxide entered the matrix. (ii) Superoxide-induced uncoupling was abolished by low concentrations of the mitochondrially targeted antioxidants 10-(6'-ubiquinonyl)decyltriphenylphosphonium (mitoQ) or 2-[2-(triphenylphosphonio)ethyl]-3,4-dihydro-2,5,7,8-tetramethyl-2H-1-benzopyran-6-ol bromide (mitoVit E), which are ubiquinone (Q) or tocopherol derivatives targeted to the matrix by covalent attachment to triphenylphosphonium cation. However, superoxide-induced uncoupling was not affected by similar concentrations of the nontargeted antioxidants Q(o), Q(1), decylubiquinone, vitamin E, or 6-hydroxy-2,5,7,8-tetramethylchroman 2-carboxylic acid (TROLOX) or of the mitochondrially targeted but redox-inactive analogs decyltriphenylphosphonium or 4-chlorobutyltriphenylphosphonium. Thus matrix superoxide appears to be necessary for activation of UCP2 by exogenous superoxide. (iii) When the reduced to oxidized ratio of mitoQ accumulated by mitochondria was increased by inhibiting cytochrome oxidase, it induced nucleotide-sensitive uncoupling that was not inhibited by external superoxide dismutase. Under these conditions quinols are known to produce superoxide, and because mitoQ is localized within the mitochondrial matrix this suggests that production of superoxide in the matrix was sufficient to activate UCP2. Furthermore, the superoxide

Immunogold electron microscopic localization of timothy grass (Phleum pratense) pollen major allergens Phl p I and Phl p V after anhydrous fixation in acrolein vapor

NARCIS (Netherlands)

Grote, M.; Dolecek, C.; van Ree, R.; Valenta, R.

1994-01-01

We used the vapor phase of acrolein as an anhydrous fixative for timothy grass pollen in an immunogold double-labeling localization study of two different major allergens, Phl p I and Phl p V. More than 48 hr of fixation were needed for the subcellular pollen structures to be satisfactorily

Influence of tool pin in friction stir welding on activated carbon reinforced aluminium metal matrix composite

Science.gov (United States)

DijuSamuel, G.; Raja Dhas, J. Edwin

2017-10-01

This paper focus on impact of tool pin in friction stir welding on activated carbon reinforced aluminium metal matrix composite. For fabrication of metal matrix composite AA6061 is used as matrix and activated carbon is used as reinforcement and it is casted using modified stir casting technique. After casting metal matrix composite has undergone various microstructure tests like SEM,EDAX and XRD. FSW is carried out in this metal matrix composite by choosing various tool pin profile like square,round,Threaded round, hexagon and taper. The quality of welded plates is measured in terms of ultimate tensile strength and hardness.

Matrix viscoplasticity and its shielding by active mechanics in microtissue models: experiments and mathematical modeling

Science.gov (United States)

Liu, Alan S.; Wang, Hailong; Copeland, Craig R.; Chen, Christopher S.; Shenoy, Vivek B.; Reich, Daniel H.

2016-01-01

The biomechanical behavior of tissues under mechanical stimulation is critically important to physiological function. We report a combined experimental and modeling study of bioengineered 3D smooth muscle microtissues that reveals a previously unappreciated interaction between active cell mechanics and the viscoplastic properties of the extracellular matrix. The microtissues’ response to stretch/unstretch actuations, as probed by microcantilever force sensors, was dominated by cellular actomyosin dynamics. However, cell lysis revealed a viscoplastic response of the underlying model collagen/fibrin matrix. A model coupling Hill-type actomyosin dynamics with a plastic perfectly viscoplastic description of the matrix quantitatively accounts for the microtissue dynamics, including notably the cells’ shielding of the matrix plasticity. Stretch measurements of single cells confirmed the active cell dynamics, and were well described by a single-cell version of our model. These results reveal the need for new focus on matrix plasticity and its interactions with active cell mechanics in describing tissue dynamics. PMID:27671239

VANGL2 interacts with integrin αv to regulate matrix metalloproteinase activity and cell adhesion to the extracellular matrix.

Science.gov (United States)

Jessen, Tammy N; Jessen, Jason R

2017-12-15

Planar cell polarity (PCP) proteins are implicated in a variety of morphogenetic processes including embryonic cell migration and potentially cancer progression. During zebrafish gastrulation, the transmembrane protein Vang-like 2 (VANGL2) is required for PCP and directed cell migration. These cell behaviors occur in the context of a fibrillar extracellular matrix (ECM). While it is thought that interactions with the ECM regulate cell migration, it is unclear how PCP proteins such as VANGL2 influence these events. Using an in vitro cell culture model system, we previously showed that human VANGL2 negatively regulates membrane type-1 matrix metalloproteinase (MMP14) and activation of secreted matrix metalloproteinase 2 (MMP2). Here, we investigated the functional relationship between VANGL2, integrin αvβ3, and MMP2 activation. We provide evidence that VANGL2 regulates cell surface integrin αvβ3 expression and adhesion to fibronectin, laminin, and vitronectin. Inhibition of MMP14/MMP2 activity suppressed the cell adhesion defect in VANGL2 knockdown cells. Furthermore, our data show that MMP14 and integrin αv are required for increased proteolysis by VANGL2 knockdown cells. Lastly, we have identified integrin αvβ3 as a novel VANGL2 binding partner. Together, these findings begin to dissect the molecular underpinnings of how VANGL2 regulates MMP activity and cell adhesion to the ECM. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Platelet activation by extracellular matrix proteins in haemostasis and thrombosis.

Science.gov (United States)

Watson, Steve P

2009-01-01

The prevention of excessive blood loss to avoid fatal haemorrhage is a pivotal process for all organisms possessing a circulatory system. Increased circulating blood volume and pressure, as required in larger animals, make this process all the more important and challenging. It is essential to have a powerful and rapid system to detect damage and generate an effective seal, and which is also exquisitely regulated to prevent unwanted, excessive or systemic activation so as to avoid blockage of vessels. Thus, a highly specialised and efficient haemostatic system has evolved that consists of cellular (platelets) and protein (coagulation factors) components. Importantly, this is able to support haemostasis in both the low shear environment of the venous system and the high shear environment of the arterial system. Endothelial cells, lining the entire circulation system, play a crucial role in the delicate balance between activation and inhibition of the haemostatic system. An intact and healthy endothelium supports blood flow by preventing attachment of cells and proteins which is required for initiation of coagulation and platelet activation. Endothelial cells produce and release the two powerful soluble inhibitors of platelet activation, nitric oxide and prostacyclin, and express high levels of CD39 which rapidly metabolises the major platelet feedback agonist, ADP. This antithrombotic environment however can rapidly change following activation or removal of endothelial cells through injury or rupture of atherosclerotic plaques. Loss of endothelial cells exposes the subendothelial extracellular matrix which creates strong signals for activation of the haemostatic system including powerful platelet adhesion and activation. Quantitative and qualitative changes in the composition of the subendothelial extracellular matrix influence these prothrombotic characteristics with life threatening thrombotic and bleeding complications, as illustrated by formation of

Conversion Matrix Analysis of GaAs HEMT Active Gilbert Cell Mixers

DEFF Research Database (Denmark)

Jiang, Chenhui; Johansen, Tom Keinicke; Krozer, Viktor

2006-01-01

In this paper, the nonlinear model of the GaAs HEMT active Gilbert cell mixer is investigated. Based on the model, the conversion gain expression of active Gilbert cell mixers is derived theoretically by using conversion matrix analysis method. The expression is verified by harmonic balance simul...

Acrolein, A Reactive Product of Lipid Peroxidation, Induces Oxidative Modification of Cytochrome c

Energy Technology Data Exchange (ETDEWEB)

Kang, Jung Hoon [Cheongju Univ., Cheongju (Korea, Republic of)

2013-11-15

Acrolein (ACR) is a well-known carbonyl toxin produced by lipid peroxidation of polyunsaturated fatty acids, which is involved in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). In Alzheimer's brain, ACR was found to be elevated in hippocampus and temporal cortex where oxidative stress is high. In this study, we evaluated oxidative modification of cytochrome c occurring after incubation with ACR. When cytochrome c was incubated with ACR, protein aggregation increased in a dose-dependent manner. The formation of carbonyl compounds and the release of iron were obtained in ACR-treated cytochrome c. Reactive oxygen species scavengers and iron specific chelator inhibited the ACR-mediated cytochrome c modification and carbonyl compound formation. Our data demonstrate that oxidative damage of cytochrome c by ACR might induce disruption of cyotochrome c structure and iron mishandling as a contributing factor to the pathology of AD.

Acrolein, A Reactive Product of Lipid Peroxidation, Induces Oxidative Modification of Cytochrome c

International Nuclear Information System (INIS)

Kang, Jung Hoon

2013-01-01

Acrolein (ACR) is a well-known carbonyl toxin produced by lipid peroxidation of polyunsaturated fatty acids, which is involved in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). In Alzheimer's brain, ACR was found to be elevated in hippocampus and temporal cortex where oxidative stress is high. In this study, we evaluated oxidative modification of cytochrome c occurring after incubation with ACR. When cytochrome c was incubated with ACR, protein aggregation increased in a dose-dependent manner. The formation of carbonyl compounds and the release of iron were obtained in ACR-treated cytochrome c. Reactive oxygen species scavengers and iron specific chelator inhibited the ACR-mediated cytochrome c modification and carbonyl compound formation. Our data demonstrate that oxidative damage of cytochrome c by ACR might induce disruption of cyotochrome c structure and iron mishandling as a contributing factor to the pathology of AD

EMMPRIN mediates beta-adrenergic receptor-stimulated matrix metalloproteinase activity in cardiac myocytes.

OpenAIRE

Siwik Deborah A; Kuster Gabriela M; Brahmbhatt Jamin V; Zaidi Zaheer; Malik Julia; Ooi Henry; Ghorayeb Ghassan

2008-01-01

Extracellular matrix metalloproteinase inducer (EMMPRIN) expression is increased in myocardium from patients with dilated cardiomyopathy and animal models of heart failure. However little is known about the regulated expression or functional role of EMMPRIN in the myocardium. In rat cardiac cells EMMPRIN is expressed on myocytes but not endothelial cells or fibroblasts. Therefore we tested the hypothesis that EMMPRIN expression regulates matrix metalloproteinase (MMP) activity in rat ventricu...

Matrix metalloproteinases (MMP) and cathepsin K contribute differently to osteoclastic activities

DEFF Research Database (Denmark)

Delaissé, Jean-Marie; Andersen, Thomas L; Engsig, Michael T

2003-01-01

The best established proteolytic event of osteoclasts is bone matrix solubilization by the cysteine proteinase cathepsin K. Here, however, we draw the attention on osteoclastic activities depending on matrix metalloproteinases (MMPs). We discuss the observations supporting that MMPs contribute...... significantly to bone matrix solubilization in specific areas of the skeleton and in some developmental and pathological situations. Our discussion takes into account (1) the characteristics of the bone remodeling persisting in the absence of cathepsin K, (2) the ultrastructure of the resorption zone...... in response to inactivation of MMPs and of cathepsin K in different bone types, (3) bone resorption levels in MMP knockout mice compared to wild-type mice, (4) the identification of MMPs in osteoclasts and surrounding cells, and (5) the effect of different bone pathologies on the serum concentrations...

Analysis of Enzymatic Activity of Matrix Metalloproteinase (MMP) by Collagen Zymography in Melanoma.

Science.gov (United States)

Walia, Vijay; Samuels, Yardena

2018-01-01

Protein zymography is the most commonly used technique to study the enzymatic activity of matrix metalloproteinases (MMPs) and their inhibitors. MMPs are proteolytic enzymes that promote extracellular matrix degradation. MMPs are frequently mutated in malignant melanomas as well as other cancers and are linked to increasing incidence of tumor metastasis. Substrate zymography characterizes MMP activity by their ability to degrade preferred substrates. Here we describe the collagen zymography technique to measure the active or latent form of MMPs using MMP-8 as an example, which is a frequently mutated MMP family member in malignant melanomas. The same technique can be used with the modification of substrate to detect metalloproteinase activity of other MMPs. Both wild-type and mutated forms of MMPs can be analyzed using a single gel using this method.

Hydrogenation of the alpha,beta-Unsaturated Aldehydes Acrolein, Crotonaldehyde, and Prenal over Pt Single Crystals: A Kinetic and Sum-Frequency Generation Vibrational Spectroscopy Study

Energy Technology Data Exchange (ETDEWEB)

Kliewer, C.J.; Somorjai, G.A.

2008-11-26

Sum-frequency generation vibrational spectroscopy (SFG-VS) and kinetic measurements using gas chromatography have been used to study the surface reaction intermediates during the hydrogenation of three {alpha},{beta}-unsaturated aldehydes, acrolein, crotonaldehyde, and prenal, over Pt(111) at Torr pressures (1 Torr aldehyde, 100 Torr hydrogen) in the temperature range of 295K to 415K. SFG-VS data showed that acrolein has mixed adsorption species of {eta}{sub 2}-di-{sigma}(CC)-trans, {eta}{sub 2}-di-{sigma}(CC)-cis as well as highly coordinated {eta}{sub 3} or {eta}{sub 4} species. Crotonaldehyde adsorbed to Pt(111) as {eta}{sub 2} surface intermediates. SFG-VS during prenal hydrogenation also suggested the presence of the {eta}{sub 2} adsorption species, and became more highly coordinated as the temperature was raised to 415K, in agreement with its enhanced C=O hydrogenation. The effect of catalyst surface structure was clarified by carrying out the hydrogenation of crotonaldehyde over both Pt(111) and Pt(100) single crystals while acquiring the SFG-VS spectra in situ. Both the kinetics and SFG-VS showed little structure sensitivity. Pt(100) generated more decarbonylation 'cracking' product while Pt(111) had a higher selectivity for the formation of the desired unsaturated alcohol, crotylalcohol.

Impulsive IR-multiphoton dissociation of acrolein: observation of non-statistical product vibrational excitation in CO ( v=1-12) by time resolved IR fluorescence spectroscopy

Science.gov (United States)

Chowdhury, P. K.

2000-10-01

On IR-multiphoton excitation, vibrationally highly excited acrolein molecules undergo concerted dissociation generating CO and ethylene. The vibrationally excited products, CO and ethylene, are detected immediately following the CO 2 laser pulse by observing IR fluorescence at 4.7 and 3.2 μm, respectively. The nascent CO is formed with significant vibrational excitation, with a Boltzmann population distribution for v=1-12 levels corresponding to T v=12 950±50 K. The average vibrational energy in the product CO is found to be 26 kcal mol -1, in contrast to its statistical share of 5 kcal mol -1, available from the product energy distribution. The nascent vibrationally excited ethylene either dissociates by absorbing further infrared laser photons from the tail of the CO 2 laser pulse or relaxes by collisional deactivation. Ethylene IR-fluorescence excitation spectrum showed a structure in the quasi-continuum, with a facile resonance at 10.53 μm corresponding to the 10P(14) CO 2 laser line, which explains the higher acetylene yield observed at a higher pressure. A hydrogen atom transfer mechanism followed by C-C impulsive break in the acrolein transition state may be responsible for such non-statistical product energy distribution.

Understanding the Relationship between Red Wine Matrix, Tannin Activity, and Sensory Properties.

Science.gov (United States)

Watrelot, Aude A; Byrnes, Nadia K; Heymann, Hildegarde; Kennedy, James A

2016-11-30

One major red wine mouthfeel characteristic, astringency, is derived from grape-extracted tannins and is considered to be a result of interaction with salivary proteins and the oral mucosa. To improve our understanding of the role that the enthalpy of interaction of tannin with a hydrophobic surface (tannin activity) has in astringency perception, a chromatographic method was used to determine the tannin concentration and activity of 34 Cabernet Sauvignon wines, as well as sensory analysis done on 13 of those wines. In addition, astringency-relevant matrix parameters (pH, titratable acidity, ethanol, glucose, and fructose) were measured across all wines. Tannin activity was not significantly correlated with any matrix variables, and the perception of drying and grippy was not correlated with tannin concentration and activity. However, ethanol content was well related to mouthfeel attributes and appeared to drive perceived drying. Although fructose and glucose content were well correlated, they did not drive the perception of sweetness, which is explained by the well-known mixture suppression effect.

Bi-layered nanocomposite bandages for controlling microbial infections and overproduction of matrix metalloproteinase activity.

Science.gov (United States)

Anjana, J; Mohandas, Annapoorna; Seethalakshmy, S; Suresh, Maneesha K; Menon, Riju; Biswas, Raja; Jayakumar, R

2018-04-15

Chronic diabetic wounds is characterised by increased microbial contamination and overproduction of matrix metalloproteases that would degrade the extracellular matrix. A bi-layer bandage was developed, that promotes the inhibition of microbial infections and matrix metalloprotease (MMPs) activity. Bi-layer bandage containing benzalkonium chloride loaded gelatin nanoparticles (BZK GNPs) in chitosan-Hyaluronic acid (HA) as a bottom layer and sodium alendronate containing chitosan as top layer was developed. We hypothesized that the chitosan-gelatin top layer with sodium alendronate could inhibit the MMPs activity, whereas the chitosan-HA bottom layer with BZK GNPs (240±66nm) would enable the elimination of microbes. The porosity, swelling and degradation nature of the prepared Bi-layered bandage was studied. The bottom layer could degrade within 4days whereas the top layer remained upto 7days. The antimicrobial activity of the BZK NPs loaded bandage was determined using normal and clinical strains. Gelatin zymography shows that the proteolytic activity of MMP was inhibited by the bandage. Copyright © 2017 Elsevier B.V. All rights reserved.

Antibacterial and anti-breast cancer cell line activities of ...

African Journals Online (AJOL)

against acrolein toxicity in vitro, and against stroke in a mouse model [13]. Chang et al. [14] and Ayala-Zavala et al. [6] found that extracts from P. merrillii, P. gilvus, P. rimosus and P. badius have antioxidant activity. Moreover, the extracts from P. gilvus, P. rimosus and P. badius could inhibit growth of the fungus Alternaria.

Time dependent transition of the levels of protein-conjugated acrolein (PC-Acro), IL-6 and CRP in plasma during stroke.

Science.gov (United States)

Yoshida, Madoka; Kato, Naoki; Uemura, Takeshi; Mizoi, Mutsumi; Nakamura, Mizuho; Saiki, Ryotaro; Hatano, Keisuke; Sato, Kunitomo; Kakizaki, Shota; Nakamura, Aya; Ishii, Takuya; Terao, Tohru; Murayama, Yuichi; Kashiwagi, Keiko; Igarashi, Kazuei

2017-06-01

Measurement of plasma levels of protein-conjugated acrolein (PC-Acro) together with IL-6 and CRP can be used to identify silent brain infarction (SBI) with high sensitivity and specificity. The aim of this study was to determine how these biomarkers vary during stroke. Levels of PC-Acro, IL-6 and CRP in plasma were measured on day 0, 2, 7 and 14 after the onset of ischemic or hemorrhagic stroke. After the onset of stroke, the level of PC-Acro in plasma was elevated corresponding to the size of stroke. It returned to near control levels by day 2, and remained similar through day 14. The degree of the decrease in PC-Acro on day 2 was greater when the size of brain infarction or hemorrhage was larger. An increase in IL-6 and CRP occurred after the increase in PC-Acro, and it was well correlated with the size of the injury following infarction or hemorrhage. The results suggest that acrolein becomes a trigger for the production of IL-6 and CRP, as previously observed in a mouse model of stroke and in cell culture systems. The increase in IL-6 and CRP was also correlated with poor outcome judging from mRS. The results indicate that the degree of the decrease in PC-Acro and the increase in IL-6 and CRP from day 0 to day 2 was correlated with the size of brain infarction, and the increase in IL-6 and CRP with poor outcome at discharge.

Plastic Substrate Active Matrix Displays Final Report CRADA No. TC-2011-00

Energy Technology Data Exchange (ETDEWEB)

Bernhardt, A. F. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Smith, P. M. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

2017-09-28

This project was a collaborative effort between the University of California, Lawrence Livermore National Laboratory (LLNL) and FlexICs, Inc. to develop thin film transistor (TFT) electronics for active matrix displays.

Analysis of methods for calculating the transition frequencies of the torsional vibration of acrolein isomers in the ground ( S 0) electronic state

Science.gov (United States)

Koroleva, L. A.; Tyulin, V. I.; Matveev, V. K.; Pentin, Yu. A.

2013-05-01

B3LYP, MP2, CCSD(T), and MP4/MP2 in the 6-311G( d, p), 6-311++G( d, p), cc-pVTZ, aug-cc-pVTZ bases used to calculate the transition frequencies of torsional vibration of trans- and cis-isomers of acrolein in the ground electronic state ( S 0) are analyzed. It is found that for trans-isomers, all methods of calculation except for B3LYP in the cc-pVTZ basis yield good agreement between the calculated and experimental values. It is noted that for the cis-isomer of acrolein, no method of calculation confirms the experimental value of the frequency of torsional vibration (138 cm-1). It is shown that the calculated and experimental values for obertones at 273.0 cm-1 and other transitions of torsional vibration are different for this isomer in particular. However, it is established that in some calculation methods (B3LYP, MP2), the frequency of the torsional vibration of the cis-isomer coincides with another experimental value of this frequency (166.5 cm-1). It is concluded that in analyzing the vibrational structure of the UV spectrum, the calculated and experimental values of its obertone (331.3 cm-1) coincide, along with its frequency. It is also noted that the frequency of torsional vibration for the cis-isomer (166.5 cm-1) can also be found in other experimental works if we change the allocation of torsional transition 18{1/1}.

Peptide-Based Selective Inhibitors of Matrix Metalloproteinase-Mediated Activities

Directory of Open Access Journals (Sweden)

Margaret W. Ndinguri

2012-11-01

Full Text Available The matrix metalloproteinases (MMPs exhibit a broad array of activities, some catalytic and some non-catalytic in nature. An overall lack of selectivity has rendered small molecule, active site targeted MMP inhibitors problematic in execution. Inhibitors that favor few or individual members of the MMP family often take advantage of interactions outside the enzyme active site. We presently focus on peptide-based MMP inhibitors and probes that do not incorporate conventional Zn2+ binding groups. In some cases, these inhibitors and probes function by binding only secondary binding sites (exosites, while others bind both exosites and the active site. A myriad of MMP mediated-activities beyond selective catalysis can be inhibited by peptides, particularly cell adhesion, proliferation, motility, and invasion. Selective MMP binding peptides comprise highly customizable, unique imaging agents. Areas of needed improvement for MMP targeting peptides include binding affinity and stability.

On the influence of matrix's heterogeneity on uncertainty of gamma-spectrometry at activity assay of radioactive waste

Directory of Open Access Journals (Sweden)

V. S. Prokopenko

2009-09-01

Full Text Available The influence of the waste matrix heterogeneity on the flux density value of initial gamma quanta at the transport of quanta in the matrix was considered. It is shown that the waste heterogeneity leads to the positive shift of the average flux density value comparing with corresponding value for homogeneous waste if average value of the attenuation factor in heterogeneous matrix is equal to the attenuation factor of homogeneous matrix. Due to this the activity assay of heterogeneous waste by a technique which was calibrated by using a homogeneous standard (surrogate container the measurement results will be positively shifted, or, in other words, conservative estimation of the waste activity will be obtained.

Differential in vivo zymography: a method for observing matrix metalloproteinase activity in the zebrafish embryo.

Science.gov (United States)

Keow, Jonathan Y; Herrmann, Kurt M; Crawford, Bryan D

2011-04-01

Investigations into the molecular mechanisms of, and cellular signaling pathways modulating ECM remodeling are especially challenging due to the complex post-translational regulation of the primary effectors of ECM catabolism - the matrix metalloproteinases (MMPs). Recently a variety of approaches to the detection of MMP activity have been developed, and the prospect of visualizing ECM remodeling activity in living tissues is now opening exciting avenues of research for matrix biologists. In particular the use of FRET-quenched MMP substrates, which generate a fluorescent signal upon hydrolysis, is becoming increasingly popular, especially because linkers with defined and/or restricted proteolytic sensitivity can be used to bind fluorophore-quencher pairs, making these probes useful in characterizing the activity of specific proteases. We have taken advantage of the transparency and amenability to reverse genetics of the zebrafish embryo, in combination with these fluorogenic MMP substrates, to develop a multiplex in vivo assay for MMP activity that we dub "differential in vivo zymography." Copyright © 2011 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

Ramiprilate inhibits functional matrix metalloproteinase activity in Crohn's disease fistulas

DEFF Research Database (Denmark)

Efsen, Eva; Saermark, Torben; Hansen, Alastair

2011-01-01

Increased expression of matrix metalloproteinase (MMP)-2, -3 and -9 has been demonstrated in Crohn's disease fistulas, but it is unknown whether these enzymes are biologically active and represent a therapeutic target. Therefore, we investigated the proteolytic activity of MMPs in fistula tissue...... from six controls were also included. Total functional MMP activity was measured by a high-pressure liquid chromatography (HPLC)-based, fluorogenic MMP-substrate cleavage assay, and the specific activity of MMP-2, -3 and -9 by the MMP Biotrak Activity Assay. The MMP inhibitors comprised ethylene......-9.83) compared with non-Crohn's fistulas, [0.32 ng/ml, range 0-2.66, (p MMP-9 activity [0.64 ng/ml, range 0-5.66 and 0.17 ng/ml, range 0-1.1, respectively (p MMP activity level by 42% and suppressed the specific MMP-3...

Risk matrix model applied to the outsourcing of logistics' activities

Directory of Open Access Journals (Sweden)

Fouad Jawab

2015-09-01

Full Text Available Purpose: This paper proposes the application of the risk matrix model in the field of logistics outsourcing. Such an application can serve as the basis for decision making regarding the conduct of a risk management in the logistics outsourcing process and allow its prevention. Design/methodology/approach: This study is based on the risk management of logistics outsourcing in the field of the retail sector in Morocco. The authors identify all possible risks and then classify and prioritize them using the Risk Matrix Model. Finally, we have come to four possible decisions for the identified risks. The analysis was made possible through interviews and discussions with the heads of departments and agents who are directly involved in each outsourced activity. Findings and Originality/value: It is possible to improve the risk matrix model by proposing more personalized prevention measures according to each company that operates in the mass-market retailing. Originality/value: This study is the only one made in the process of logistics outsourcing in the retail sector in Morocco through Label’vie as a case study. First, we had identified as thorough as we could all possible risks, then we applied the Risk Matrix Model to sort them out in an ascending order of importance and criticality. As a result, we could hand out to the decision-makers the mapping for an effective control of risks and a better guiding of the process of risk management.

AMP-Activated Protein Kinase Alleviates Extracellular Matrix Accumulation in High Glucose-Induced Renal Fibroblasts through mTOR Signaling Pathway

Directory of Open Access Journals (Sweden)

Xia Luo

2015-01-01

Full Text Available Background/Aims: Extracellular matrix accumulation contributes significantly to the pathogenesis of diabetic nephropathy. Although AMP-activated protein kinase (AMPK has been found to inhibit extracellular matrix synthesis by experiments in vivo and vitro, its role in alleviating the deposition of extracellular matrix in renal interstitial fibroblasts has not been well defined. Methods: Currently, we conducted this study to investigate the effects of AMPK on high glucose-induced extracellular matrix synthesis and involved intracellular signaling pathway by using western blot in the kidney fibroblast cell line (NRK-49f. Results: Collagen IV protein levels were significantly increased by high glucose in a time-dependent manner. This was associated with a decrease in Thr72 phosphorylation of AMPK and an increase in phosphorylation of mTOR on Ser2448. High glucose-induced extracellular matrix accumulation and mTOR activation were significantly inhibited by the co-treatment of rAAV-AMPKα1312 (encoding constitutively active AMPKα1 whereas activated by r-AAV-AMPKα1D157A (encoding dominant negative AMPKα1. In cultured renal fibroblasts, overexpression of AMPKα1D157A upregulated mTOR signaling and matrix synthesis, which were ameliorated by co-treatment with the inhibitor of mTOR, rapamycin. Conclusion: Collectively, these findings indicate that AMPK exerts renoprotective effects by inhibiting the accumulation of extracellular matrix through mTOR signaling pathway.

Improvement of the matrix effect compensation in active neutron measurement by simulated annealing algorithm (June 2009)

International Nuclear Information System (INIS)

Raoux, A. C.; Loridon, J.; Mariani, A.; Passard, C.

2009-01-01

Active neutron measurements such as the Differential Die-Away (DDA) technique involving pulsed neutron generator, are widely applied to determine the fissile content of waste packages. Unfortunately, the main drawback of such techniques is coming from the lack of knowledge of the waste matrix composition. Thus, the matrix effect correction for the DDA measurement is an essential improvement in the field of fissile material content determination. Different solutions have been developed to compensate the effect of the matrix on the neutron measurement interpretation. In this context, this paper describes an innovative matrix correction method we have developed with the goal of increasing the accuracy of the matrix effect correction and reducing the measurement time. The implementation of this method is based on the analysis of the raw signal with an optimisation algorithm called the simulated annealing algorithm. This algorithm needs a reference data base of Multi-Channel Scaling (MCS) spectra, to fit the raw signal. The construction of the MCS library involves a learning phase to define and acquire the DDA signals. This database has been provided by a set of active signals from experimental matrices (mock-up waste drums of 118 litres) recorded in a specific device dedicated to neutron measurement research and development of the Nuclear Measurement Laboratory of CEA-Cadarache, called PROMETHEE 6. The simulated annealing algorithm is applied to make use of the effect of the matrices on the total active signal of DDA measurement. Furthermore, as this algorithm is directly applied to the raw active signal, it is very useful when active background contributions can not be easily estimated and removed. Most of the cases tested during this work which represents the feasibility phase of the method, are within a 4% agreement interval with the expected experimental value. Moreover, one can notice that without any compensation of the matrix effect, the classical DDA prompt

Improvement of the matrix effect compensation in active neutron measurement by simulated annealing algorithm (June 2009)

Energy Technology Data Exchange (ETDEWEB)

Raoux, A. C.; Loridon, J.; Mariani, A.; Passard, C. [French Atomic Energy Commission, DEN, Cadarache, F-3108 Saint-Paul-Lez-Durance (France)

2009-07-01

Active neutron measurements such as the Differential Die-Away (DDA) technique involving pulsed neutron generator, are widely applied to determine the fissile content of waste packages. Unfortunately, the main drawback of such techniques is coming from the lack of knowledge of the waste matrix composition. Thus, the matrix effect correction for the DDA measurement is an essential improvement in the field of fissile material content determination. Different solutions have been developed to compensate the effect of the matrix on the neutron measurement interpretation. In this context, this paper describes an innovative matrix correction method we have developed with the goal of increasing the accuracy of the matrix effect correction and reducing the measurement time. The implementation of this method is based on the analysis of the raw signal with an optimisation algorithm called the simulated annealing algorithm. This algorithm needs a reference data base of Multi-Channel Scaling (MCS) spectra, to fit the raw signal. The construction of the MCS library involves a learning phase to define and acquire the DDA signals. This database has been provided by a set of active signals from experimental matrices (mock-up waste drums of 118 litres) recorded in a specific device dedicated to neutron measurement research and development of the Nuclear Measurement Laboratory of CEA-Cadarache, called PROMETHEE 6. The simulated annealing algorithm is applied to make use of the effect of the matrices on the total active signal of DDA measurement. Furthermore, as this algorithm is directly applied to the raw active signal, it is very useful when active background contributions can not be easily estimated and removed. Most of the cases tested during this work which represents the feasibility phase of the method, are within a 4% agreement interval with the expected experimental value. Moreover, one can notice that without any compensation of the matrix effect, the classical DDA prompt

Aldehyde-sequestering drugs: tools for studying protein damage by lipid peroxidation products.

Science.gov (United States)

Burcham, Philip C; Kaminskas, Lisa M; Fontaine, Frank R; Petersen, Dennis R; Pyke, Simon M

2002-12-27

Elevated levels of reactive alpha,beta-unsaturated aldehydes (e.g. malondialdehyde, 4-hydroxynonenal and acrolein) in the affected tissues of various degenerative conditions suggest these substances are active propagators of the disease process. One experimental approach to attenuating damage by these intermediates employs 'aldehyde-sequestering drugs' as sacrificial nucleophiles, thereby sparing cell macromolecules and perhaps slowing disease progression. Drugs with demonstrated trapping activity toward lipid-derived aldehydes include various amine compounds such as aminoguanidine, carnosine and pyridoxamine. We have focused on identifying scavengers of acrolein, perhaps the most toxic aldehyde formed during lipid peroxidation cascades. Various phthalazine compounds (hydralazine and dihydralazine) were found to trap acrolein readily, forming hydrazone derivatives in a rapid Schiff-type reaction. These compounds strongly protect against acrolein-mediated toxicity in isolated hepatocytes.

DANTE, Activation Analysis Neutron Spectra Unfolding by Covariance Matrix Method

International Nuclear Information System (INIS)

Petilli, M.

1981-01-01

1 - Description of problem or function: The program evaluates activation measurements of reactor neutron spectra and unfolds the results for dosimetry purposes. Different evaluation options are foreseen: absolute or relative fluxes and different iteration algorithms. 2 - Method of solution: A least-square fit method is used. A correlation between available data and their uncertainties has been introduced by means of flux and activity variance-covariance matrices. Cross sections are assumed to be constant, i.e. with variance-covariance matrix equal to zero. The Lagrange multipliers method has been used for calculating the solution. 3 - Restrictions on the complexity of the problem: 9 activation experiments can be analyzed. 75 energy groups are accepted

Pesticide-exposure Matrix helps identify active ingredients in pesticides used in past years

Science.gov (United States)

Pesticide-exposure Matrix was developed to help epidemiologists and other researchers identify the active ingredients to which people were likely exposed when their homes and gardens were treated for pests in past years

PPARγ agonist pioglitazone reduces matrix metalloproteinase-9 activity and neuronal damage after focal cerebral ischemia

International Nuclear Information System (INIS)

Lee, Seong-Ryong; Kim, Hahn-Young; Hong, Jung-Suk; Baek, Won-Ki; Park, Jong-Wook

2009-01-01

Pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, has shown protective effects against ischemic insult in various tissues. Pioglitazone is also reported to reduce matrix metalloproteinase (MMP) activity. MMPs can remodel extracellular matrix components in many pathological conditions. The current study was designed to investigate whether the neuroprotection of pioglitazone is related to its MMP inhibition in focal cerebral ischemia. Mice were subjected to 90 min focal ischemia and reperfusion. In gel zymography, pioglitazone reduced the upregulation of active form of MMP-9 after ischemia. In in situ zymograms, pioglitazone also reduced the gelatinase activity induced by ischemia. After co-incubation with pioglitazone, in situ gelatinase activity was directly reduced. Pioglitazone reduced the infarct volume significantly compared with controls. These results demonstrate that pioglitazone may reduce MMP-9 activity and neuronal damage following focal ischemia. The reduction of MMP-9 activity may have a possible therapeutic effect for the management of brain injury after focal ischemia.

Neutron activation analysis on determination of arsenic in biological matrixes

International Nuclear Information System (INIS)

Menezes, Maria Angela de B.C.; Silva, Maria Aparecida

2013-01-01

Aiming at giving support to the Worker's Health Awareness Program of the Municipal Department of Health of Belo Horizonte, an assessment related arsenic was carried out in two galvanising factories by means of hair and toenail samples analysis as biomonitors. The arsenic was determined in all matrixes from the factories where gold electrodeposition process was applied. This is because arsenic salts are usually added to gold bath to improve the metal covering. The high concentration results surprised the health surveillance professionals, and alerted for the need of assessing the influence of a long-term exposure. Studies concerning galvanising process have usually been developed broaching many aspects, but so far few works has pointed out the detection and measurement of other elements like arsenic. The k 0 -Instrumental Neutron Activation method was applied confirming to be a suitable technique on determination of arsenic in biological matrixes. (author)

Neutron activation analysis on determination of arsenic in biological matrixes

Energy Technology Data Exchange (ETDEWEB)

Menezes, Maria Angela de B.C.; Silva, Maria Aparecida, E-mail: menezes@cdtn.br, E-mail: cida@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)

2013-07-01

Aiming at giving support to the Worker's Health Awareness Program of the Municipal Department of Health of Belo Horizonte, an assessment related arsenic was carried out in two galvanising factories by means of hair and toenail samples analysis as biomonitors. The arsenic was determined in all matrixes from the factories where gold electrodeposition process was applied. This is because arsenic salts are usually added to gold bath to improve the metal covering. The high concentration results surprised the health surveillance professionals, and alerted for the need of assessing the influence of a long-term exposure. Studies concerning galvanising process have usually been developed broaching many aspects, but so far few works has pointed out the detection and measurement of other elements like arsenic. The k{sub 0}-Instrumental Neutron Activation method was applied confirming to be a suitable technique on determination of arsenic in biological matrixes. (author)

Activity and expression of urokinase-type plasminogen activator and matrix metalloproteinases in human colorectal cancer

International Nuclear Information System (INIS)

Kim, Tae-Dong; Song, Kyoung-Sub; Li, Ge; Choi, Hoon; Park, Hae-Duck; Lim, Kyu; Hwang, Byung-Doo; Yoon, Wan-Hee

2006-01-01

Matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and urokinase-type plasminogen activator (uPA) are involved in colorectal cancer invasion and metastasis. There is still debate whether the activity of MMP-2 and MMP-9 differs between tumors located in the colon and rectum. We designed this study to determine any differences in the expression of MMP-2, MMP-9 and uPA system between colon and rectal cancer tissues. Cancer tissue samples were obtained from colon carcinoma (n = 12) and rectal carcinomas (n = 10). MMP-2 and MMP-9 levels were examined using gelatin zymography and Western blotting; their endogenous inhibitors, tissue inhibitor of metalloproteinase-2 (TIMP-2) and tissue inhibitor of metalloproteinase-1 (TIMP-1), were assessed by Western blotting. uPA, uPAR and PAI-1 were examined using enzyme-linked immunosorbent assay (ELISA). The activity of uPA was assessed by casein-plasminogen zymography. In both colon and rectal tumors, MMP-2, MMP-9 and TIMP-1 protein levels were higher than in corresponding paired normal mucosa, while TIMP-2 level in tumors was significantly lower than in normal mucosa. The enzyme activities or protein levels of MMP-2, MMP-9 and their endogenous inhibitors did not reach a statistically significant difference between colon and rectal cancer compared with their normal mucosa. In rectal tumors, there was an increased activity of uPA compared with the activity in colon tumors (P = 0.0266), however urokinase-type plasminogen activator receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1) showed no significant difference between colon and rectal cancer tissues. These findings suggest that uPA may be expressed differentially in colon and rectal cancers, however, the activities or protein levels of MMP-2, MMP-9, TIMP-1, TIMP-2, PAI-1 and uPAR are not affected by tumor location in the colon or the rectum

Matrix Metalloproteinase Activities And Some Hormones Levels During Gestation Period In Cows

International Nuclear Information System (INIS)

TEAMA, F.E.

2010-01-01

Many factors including proteases, growth factors and hormones play important role in implantation and tissue remodelling of endometrium during different stages of gestation.Matrix metalloproteinases (MMP) such as gelatinases mainly MMP-2 and MMP-9 are implicated in the degradation of extracellular matrix for tissue remodelling.The aim of the present study is to evaluate the role of matrix metalloproteinases (MMP-2 and MMP-9) and hormones including progesterone (P4) and estradiol (E2) in the gestation process. The enzyme activities of MMP-2 and MMP-9 in serum collected from 8 Brown Swiss cows during different periods of gestation using zymography technique were examined. Hormonal levels for both P4 and E2 were determined using radioimmunoassay and also total proteins were estimated. A significant increase in MMP-2 activity by about 98%, 115% and 110% in the 1 st , 2 nd and 3 rd trimester of gestation were recorded, respectively, whereas it increased to be 185% in the pre-partum period as compared to non-pregnant cows (P nd trimester was recorded where the activity elevated by about 85% of non-pregnant controls (P st and 3 rd trimesters, the enzyme activity was not detectable. P4 level was increased gradually until its maximum at the 2 nd trimester then decreased until pre-partum.E2 level recorded too little increase at the beginning of the 1 st and 2 nd trimesters then sharply increased at the 3 rd one reached its maximum at pre-partum. There were significant decreases in total protein concentrations in the 2 nd and 3 rd trimesters then reached the lowest level before parturition .It could be concluded that the high activity of MMP-2 but not MMP-9 enzyme has important role throughout the gestation period in cows and P4 has important role in the fetal growth and E2 in the placental loss.

Elevated levels of mercapturic acids of acrolein and crotonaldehyde in the urine of Chinese women in Singapore who regularly cook at home.

Directory of Open Access Journals (Sweden)

Stephen S Hecht

Full Text Available Lung cancer is unusually common among non-smoking women in Southeastern Asia but the causes of this frequently fatal disease are not well understood. Several epidemiology studies indicate that inhalation of fumes from high temperature Chinese style cooking with a wok may be a cause. Only one previous study investigated uptake of potential toxicants and carcinogens by women who cook with a wok. We enrolled three-hundred twenty-eight non-smoking women from Singapore for this study. Each provided a spot urine sample and answered a questionnaire concerning their cooking habits and other factors. The urine samples were analyzed by liquid chromatography-tandem mass spectrometry for mercapturic acid metabolites of acrolein (3-hydroxypropylmercapturic acid, crotonaldehyde (3-hydroxy-1-methylpropylmercapturic acid, and benzene (S-phenylmercapturic acid, accepted biomarkers of uptake of these toxic and carcinogenic compounds. We observed statistically significant effects of wok cooking frequency on levels of 3-hydroxypropylmercapturic acid and 3-hydroxy-1-methylpropylmercapturic acid, but not S-phenylmercapturic acid. Women who cooked greater than 7 times per week had a geometric mean of 2600 (95% CI, 2189-3090 pmol/mg creatinine 3-hydroxypropylmercapturic acid compared to 1901 (95% CI, 1510-2395 pmol/mg creatinine when cooking less than once per week (P for trend 0.018. The corresponding values for 3-hydroxy-1-methylpropylmercapturic acid were 1167 (95% CI, 1022-1332 and 894 (95% CI, 749-1067 pmol/mg creatinine (P for trend 0.008. We conclude that frequent wok cooking leads to elevated exposure to the toxicants acrolein and crotonaldehyde, but not benzene. Kitchens should be properly ventilated to decrease exposure to potentially toxic and carcinogenic fumes produced during Chinese style wok cooking.

A new kinetic model based on the remote control mechanism to fit experimental data in the selective oxidation of propene into acrolein on biphasic catalysts

Energy Technology Data Exchange (ETDEWEB)

Abdeldayem, H.M.; Ruiz, P.; Delmon, B. [Unite de Catalyse et Chimie des Materiaux Divises, Universite Catholique de Louvain, Louvain-La-Neuve (Belgium); Thyrion, F.C. [Unite des Procedes Faculte des Sciences Appliquees, Universite Catholique de Louvain, Louvain-La-Neuve (Belgium)

1998-12-31

A new kinetic model for a more accurate and detailed fitting of the experimental data is proposed. The model is based on the remote control mechanism (RCM). The RCM assumes that some oxides (called `donors`) are able to activate molecular oxygen transforming it to very active mobile species (spillover oxygen (O{sub OS})). O{sub OS} migrates onto the surface of the other oxide (called `acceptor`) where it creates and/or regenerates the active sites during the reaction. The model contains tow terms, one considering the creation of selective sites and the other the catalytic reaction at each site. The model has been tested in the selective oxidation of propene into acrolein (T=380, 400, 420 C; oxygen and propene partial pressures between 38 and 152 Torr). Catalysts were prepared as pure MoO{sub 3} (acceptor) and their mechanical mixtures with {alpha}-Sb{sub 2}O{sub 4} (donor) in different proportions. The presence of {alpha}-Sb{sub 2}O{sub 4} changes the reaction order, the activation energy of the reaction and the number of active sites of MoO{sub 3} produced by oxygen spillover. These changes are consistent with a modification in the degree of irrigation of the surface by oxygen spillover. The fitting of the model to experimental results shows that the number of sites created by O{sub SO} increases with the amount of {alpha}-Sb{sub 2}O{sub 4}. (orig.)

High matrix metalloproteinase activity is a hallmark of periapical granulomas.

Science.gov (United States)

de Paula-Silva, Francisco Wanderley Garcia; D'Silva, Nisha J; da Silva, Léa Assed Bezerra; Kapila, Yvonne Lorraine

2009-09-01

The inability to distinguish periapical cysts from granulomas before performing root canal treatment leads to uncertainty in treatment outcomes because cysts have lower healing rates. Searching for differential expression of molecules within cysts or granulomas could provide information with regard to the identity of the lesion or suggest mechanistic differences that may form the basis for future therapeutic intervention. Thus, we investigated whether granulomas and cysts exhibit differential expression of extracellular matrix (ECM) molecules. Human periapical granulomas, periapical cysts, and healthy periodontal ligament tissues were used to investigate the differential expression of ECM molecules by microarray analysis. Because matrix metalloproteinases (MMP) showed the highest differential expression in the microarray analysis, MMPs were further examined by in situ zymography and immunohistochemistry. Data were analyzed by using one-way analysis of variance followed by the Tukey test. We observed that cysts and granulomas differentially expressed several ECM molecules, especially those from the MMP family. Compared with cysts, granulomas exhibited higher MMP enzymatic activity in areas stained for MMP-9. These areas were composed of polymorphonuclear cells (PMNs) in contrast to cysts. Similarly, MMP-13 was expressed by a greater number of cells in granulomas compared with cysts. Our findings indicate that high enzymatic MMP activity in PMNs together with MMP-9 and MMP-13 stained cells could be a molecular signature of granulomas unlike periapical cysts.

Determination of acrolein, ethanol, volatile acidity, and copper in different samples of sugarcane spirits Determinação de acroleína, etanol, acidez volátil e cobre em diferentes amostras de aguardentes de cana

Directory of Open Access Journals (Sweden)

José Masson

2012-09-01

Full Text Available Seventy-one samples of sugarcane spirits from small and average size stills produced in the northern and southern Minas Gerais (Brazil were analyzed for acrolein using HPLC (High Performance Liquid Chromatography. Ethanol and copper concentrations and volatile acidity were also determined according to methods established by the Ministry of Agriculture, Livestock and Supply (MAPA. A total of 9.85% of the samples tested showed levels of acrolein above the legal limits, while the copper concentrations of 21.00% of the samples and the volatile acidity of 8.85% of the samples were higher than the limits established by the Brazilian legislation. The concentration of acrolein varied from 0 to 21.97 mg.100 mL-1 of ethanol. However, no significant difference at 5% of significance was observed between the samples produced in the northern and southern Minas Gerais. The method used for determination of acrolein in sugarcane spirits involved the formation of a derivative with 2,4-dinitrophenylhydrazine (2,4-DNPH and subsequent analysis by HPLC.As setenta e uma amostras de aguardentes de cana coletadas em alambiques de pequeno e médio porte, provenientes das regiões norte e sul de Minas Gerais, foram avaliadas por CLAE (Cromatografia Líquida de Alta Eficiência quanto ao teor de acroleína. Avaliaram-se também as concentrações de etanol, acidez volátil e cobre, utilizando-se as metodologias estabelecidas pelo Ministério da Agricultura, Pecuária e Abastecimento (MAPA. Do total de amostras, 9,85% apresentaram níveis de acroleína acima do limite legal, 21,00% apresentaram teores de cobre e 8,85% de acidez volátil acima dos limites estabelecidos pela legislação brasileira. Os teores de acroleína variaram de 0 a 21,97 mg.100 mL-1 de etanol. Entretanto, não ocorreu diferença significativa no nível de 5% de significância entre as amostras do norte e as do sul de Minas Gerais. O método aplicado para a determinação de acroleína em aguardente de

Vibrationally specific photoionization cross sections of acrolein leading to the Χ~A' ionic state

International Nuclear Information System (INIS)

López-Domínguez, Jesús A.; Lucchese, Robert R.; Fulfer, K. D.; Hardy, David; Poliakoff, E. D.; Aguilar, A. A.

2014-01-01

The vibrational branching ratios in the photoionization of acrolein for ionization leading to the Χ ~ A ' ion state were studied. Computed logarithmic derivatives of the cross section and the corresponding experimental data derived from measured vibrational branching ratios for several normal modes (ν 9 , ν 10 , ν 11 , and ν 12 ) were found to be in relatively good agreement, particularly for the lower half of the 11–100 eV photon energy range considered. Two shape resonances have been found near photon energies of 15.5 and 23 eV in the photoionization cross section and have been demonstrated to originate from the partial cross section of the A ′ scattering symmetry. The wave functions computed at the resonance complex energies are delocalized over the whole molecule. By looking at the dependence of the cross section on the different normal mode displacements together with the wave function at the resonant energy, a qualitative explanation is given for the change of the cross sections with respect to changing geometry

Correlation between telomerase activity and matrix metalloproteinases 2 expression in gastric cancer.

Science.gov (United States)

Wang, Gang; Wang, Wenling; Zhou, Jianjiang; Yang, Xiaofeng

2013-01-01

To investigate the relationship between telomerase activity (TA) and matrix metallo proteinases 2 (MMP-2) on malignant behavior and prognosis predictable value in gastric cancer. Telomerase activity and MMP-2 protein expressions were tested in 40 gastric surgical resected cancer samples and the clinicopathological data of enrolled patients were obtained to get correlation analysis results. The expression of telomerase was up-regulated with infiltrating depth, lymph node metastasis and stage (P correlated with infiltrating depth (P < 0.05). Combined detections of telomerase activity and MMP2 protein could identify patients at high risk in disease recurrence and prognosis more efficiently.

Photolysis of allene-ozone mixtures at 647 nm in cryogenic matrices. Part 1. Formation of allene oxide

Science.gov (United States)

Singmaster, Karen A.; Pimentel, George C.

1989-03-01

Matrix studies of the photolytic reaction at 647 nm between allene and ozone were carried out at 12 K. Primary photoproducts include carbon monoxide, acrolein ( cis and trans), cyclopropanone, ketene, ethylene, allene oxide and formaldehyde. In Ar and Kr matrices both acrolein and cyclopropanone are produced in high yields, whereas in Xe matrices cyclopropanone is the major product. Infrared spectra for cyclopropanone and its oxygen-18 and deuterium substitutes are reported. The carbonyl stretch for cyclopropanone is observed at 1815 cm -1 in an Ar matrix. Also reported is the first synthesis of allene oxide. The carbon—carbon double bond stretch is observed at 1823.4 cm -1 and it exhibits a small oxygen-18 shift. The change in product distribution is discussed in terms of heavy atom spin—orbit enhancement of singlet—triplet excitation, so that in xenon reaction takes place on a triplet surface, whereas in argon it occurs on a singlet surface.

Cortisol/cortisone ratio and matrix metalloproteinase-9 activity are associated with pediatric primary hypertension.

Science.gov (United States)

Martinez-Aguayo, Alejandro; Campino, Carmen; Baudrand, Rene; Carvajal, Cristian A; García, Hernán; Aglony, Marlene; Bancalari, Rodrigo; García, Lorena; Loureiro, Carolina; Vecchiola, Andrea; Tapia-Castillo, Alejandra; Valdivia, Carolina; Sanhueza, Sebastian; Fuentes, Cristobal A; Lagos, Carlos F; Solari, Sandra; Allende, Fidel; Kalergis, Alexis M; Fardella, Carlos E

2016-09-01

To identify novel biomarkers associated with pediatric primary hypertension. We recruited 350 participants (4-16 years). Anthropometric parameters and aldosterone, plasma renin activity, cortisol, cortisone, Homeostasis Model Assessment Insulin Resistance (HOMA-IR), high-sensitivity C-reactive protein, adiponectin, IL-6, plasminogen activator inhibitor type 1 levels and matrix metalloproteinase-9 and matrix metalloproteinase-2 (MMP-9 and MMP-2) activities were measured. Genomic DNA was isolated. Patients with altered glucose metabolism, severe obesity [BMI-SD score (BMI-SDS) > 2.5], renovascular disease, primary aldosteronism and apparent mineralocorticoid excess syndrome were excluded. In selected participants (n = 320), SBP was positively correlated with BMI-SDS (r = 0.382, P cortisol/cortisone ratio (r = 0.231, P cortisol/cortisone ratio (P cortisol/cortisone ratio (OR = 3.92; 95% CI = 1.98-7.71) and increased MMP-9 activity (OR = 4.23; 95% CI = 2.15-8.32). We report that MMP-9 activity and the cortisol/cortisone ratio were higher in pediatric primary hypertensive patients, and these associations were independent of the effect of obesity. The potential role of these novel biomarkers in predicting hypertension risk and blood pressure regulation warrants further investigation.

Chromosomal loop/nuclear matrix organization of transcriptionally active and inactive RNA polymerases in HeLa nuclei.

Science.gov (United States)

Roberge, M; Dahmus, M E; Bradbury, E M

1988-06-05

The relative distribution of transcriptionally active and inactive RNA polymerases I and II between the nuclear matrix/scaffold and chromosomal loops of HeLa cells was determined. Total RNA polymerase was assessed by immunoblotting and transcribing RNA polymerase by a photoaffinity labeling technique in isolated nuclei. Nuclear matrix/scaffold was isolated by three methods using high-salt, intermediate-salt or low-salt extraction. The distribution of RNA polymerases I and II were very similar within each of the methods, but considerable differences in distributions were found between the different preparation methods. Either intermediate-salt or high-salt treatment of DNase I-digested nuclei showed significant association of RNA polymerases with the nuclear matrix. However, intermediate-salt followed by high-salt treatment released all transcribing and non-transcribing RNA polymerases. Nuclear scaffolds isolated with lithium diiodosalicylate (low-salt) contained very little of the RNA polymerases. This treatment, however, caused the dissociation of RNA polymerase II transcription complexes. These results show unambiguously that RNA polymerases, both in their active and inactive forms, are not nuclear matrix proteins. The data support models in which the transcriptional machinery moves around DNA loops during transcription.

The Exopolysaccharide Matrix

Science.gov (United States)

Koo, H.; Falsetta, M.L.; Klein, M.I.

2013-01-01

Many infectious diseases in humans are caused or exacerbated by biofilms. Dental caries is a prime example of a biofilm-dependent disease, resulting from interactions of microorganisms, host factors, and diet (sugars), which modulate the dynamic formation of biofilms on tooth surfaces. All biofilms have a microbial-derived extracellular matrix as an essential constituent. The exopolysaccharides formed through interactions between sucrose- (and starch-) and Streptococcus mutans-derived exoenzymes present in the pellicle and on microbial surfaces (including non-mutans) provide binding sites for cariogenic and other organisms. The polymers formed in situ enmesh the microorganisms while forming a matrix facilitating the assembly of three-dimensional (3D) multicellular structures that encompass a series of microenvironments and are firmly attached to teeth. The metabolic activity of microbes embedded in this exopolysaccharide-rich and diffusion-limiting matrix leads to acidification of the milieu and, eventually, acid-dissolution of enamel. Here, we discuss recent advances concerning spatio-temporal development of the exopolysaccharide matrix and its essential role in the pathogenesis of dental caries. We focus on how the matrix serves as a 3D scaffold for biofilm assembly while creating spatial heterogeneities and low-pH microenvironments/niches. Further understanding on how the matrix modulates microbial activity and virulence expression could lead to new approaches to control cariogenic biofilms. PMID:24045647

CCR5 delta32, matrix metalloproteinase-9 and disease activity in multiple sclerosis

DEFF Research Database (Denmark)

Sellebjerg, Finn; Madsen, Hans O; Jensen, Claus V

2000-01-01

Chemokines and matrix metalloproteinases (MMPs) appear to be crucial in leukocyte recruitment to the central nervous system in multiple sclerosis (MS). CCR5 delta32, a truncated allele of the CC chemokine receptor CCR5 gene encoding a non-functional receptor, did not confer protection from MS. CCR5...... delta32 was, however, associated with a lower risk of recurrent clinical disease activity. High CSF levels of MMP-9 activity were also associated with recurrent disease activity. These results directly link intrathecal inflammation to disease activity in patients with MS, suggesting that treatments...... targeting CCR5 or treatment with MMP inhibitors may attenuate disease activity in MS...

Acrolein—an α,ß-Unsaturated Aldehyde: A Review of Oral Cavity Exposure and Oral Pathology Effects

Directory of Open Access Journals (Sweden)

Dror Aizenbud

2016-07-01

Full Text Available Acrolein is a highly reactive unsaturated aldehyde widely present in the environment, particularly as a product of tobacco smoke. Our previous studies indicated the adverse consequences of even short-term acrolein exposure and proposed a molecular mechanism of its potential harmful effect on oral cavity keratinocytic cells. In this paper we chose to review the broad spectrum of acrolein sources such as pollution, food, and smoking. Consequently, in this paper we consider a high level of oral exposure to acrolein through these sources and discuss the noxious effects it has on the oral cavity including on salivary quality and contents, oral resistance to oxidative stress, and stress mechanism activation in a variety of oral cells.

Stretchable Active Matrix Temperature Sensor Array of Polyaniline Nanofibers for Electronic Skin.

Science.gov (United States)

Hong, Soo Yeong; Lee, Yong Hui; Park, Heun; Jin, Sang Woo; Jeong, Yu Ra; Yun, Junyeong; You, Ilhwan; Zi, Goangseup; Ha, Jeong Sook

2016-02-03

A stretchable polyaniline nanofiber temperature sensor array with an active matrix consisting of single-walled carbon nanotube thin-film transistors is demonstrated. The integrated temperature sensor array gives mechanical stability under biaxial stretching of 30%, and the resultant spatial temperature mapping does not show any mechanical or electrical degradation. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Glutathione S-transferases YcYfetus and YcYc - kinetic and inhibitor ...

African Journals Online (AJOL)

1991-03-16

Mar 16, 1991 ... enzyme. It is therefore attractive to suggest that should a similar situation arise in 11;110, this resistance to peroxidase inhibition may play a role in preventing ..... EFFECT OF KCI CONCENTRATION ON ACROLEIN. INHIBITION OF GSH PEROXIDASE ACTIVITY. Acrolein. KCI. " concentration concentration.

Monolithic Active Pixel Matrix with Binary Counters ASIC with nested wells

International Nuclear Information System (INIS)

Fahim, F; Deptuch, G; Holm, S; Shenai, A; Lipton, R

2013-01-01

Monolithic Active Matrix with Binary Counters (MAMBO) V ASIC has been designed for detecting and measuring low energy X-rays. A nested well structure with a buried n-well (BNW) and a deeper buried p-well (BPW) is used to electrically isolate the detector from the electronics. BNW acts as an AC ground to electrical signals and behaves as a shield. BPW allows for a homogenous electric field in the entire detector volume. The ASIC consists of a matrix of 50 × 52 pixels, each of 105x105μm 2 . Each pixel contains analog functionality accomplished by a charge preamplifier, CR-RC 2 shaper and a baseline restorer. It also contains a window comparator with Upper and Lower thresholds which can be individually trimmed by 4 bit DACs to remove systematic offsets. The hits are registered by a 12 bit counter which is reconfigured as a shift register to serially output the data from the entire ASIC.

Fully Screen-Printed, Large-Area, and Flexible Active-Matrix Electrochromic Displays Using Carbon Nanotube Thin-Film Transistors.

Science.gov (United States)

Cao, Xuan; Lau, Christian; Liu, Yihang; Wu, Fanqi; Gui, Hui; Liu, Qingzhou; Ma, Yuqiang; Wan, Haochuan; Amer, Moh R; Zhou, Chongwu

2016-11-22

Semiconducting single-wall carbon nanotubes are ideal semiconductors for printed electronics due to their advantageous electrical and mechanical properties, intrinsic printability in solution, and desirable stability in air. However, fully printed, large-area, high-performance, and flexible carbon nanotube active-matrix backplanes are still difficult to realize for future displays and sensing applications. Here, we report fully screen-printed active-matrix electrochromic displays employing carbon nanotube thin-film transistors. Our fully printed backplane shows high electrical performance with mobility of 3.92 ± 1.08 cm 2 V -1 s -1 , on-off current ratio I on /I off ∼ 10 4 , and good uniformity. The printed backplane was then monolithically integrated with an array of printed electrochromic pixels, resulting in an entirely screen-printed active-matrix electrochromic display (AMECD) with good switching characteristics, facile manufacturing, and long-term stability. Overall, our fully screen-printed AMECD is promising for the mass production of large-area and low-cost flexible displays for applications such as disposable tags, medical electronics, and smart home appliances.

High resolution in situ zymography reveals matrix metalloproteinase activity at glutamatergic synapses.

Science.gov (United States)

Gawlak, M; Górkiewicz, T; Gorlewicz, A; Konopacki, F A; Kaczmarek, L; Wilczynski, G M

2009-01-12

Synaptic plasticity involves remodeling of extracellular matrix. This is mediated, in part, by enzymes of the matrix metalloproteinase (MMP) family, in particular by gelatinase MMP-9. Accordingly, there is a need of developing methods to visualize gelatinolytic activity at the level of individual synapses, especially in the context of neurotransmitters receptors. Here we present a high-resolution fluorescent in situ zymography (ISZ), performed in thin sections of the alcohol-fixed and polyester wax-embedded brain tissue of the rat (Rattus norvegicus), which is superior to the current ISZ protocols. The method allows visualization of structural details up to the resolution-limit of light microscopy, in conjunction with immunofluorescent labeling. We used this technique to visualize and quantify gelatinolytic activity at the synapses in control and seizure-affected rat brain. In particular, we demonstrated, for the first time, frequent colocalization of gelatinase(s) with synaptic N-methyl-D-aspartic acid (NMDA)- and AMPA-type glutamate receptors. We believe that our method represents a valuable tool to study extracellular proteolytic processes at the synapses, it could be used, as well, to investigate proteinase involvement in a range of physiological and pathological phenomena in the nervous system.

Development of immobilizing matrix for radioactive hearth ash of low activity level

International Nuclear Information System (INIS)

Greben'kov, A.J.; Kopets, Z.V.; Rytvinskaya, E.V.; Vecher, V.A.

2004-01-01

The incorporation of a certain quantity of the sorbing admixtures, i.e. the clay containing about 80 mas.% of montmorillonite, natural molding flask, into an ash-cement matrix allowed obtaining the hardened compounds with radioactive ash mass fraction of 40-60 mas.%, which physicochemical characteristics are significantly better that those required by regulations. This will facilitate the development of effective low active hearth ash utilization technologies. (authors)

Correcting the effects of the matrix using capture gamma-ray spectrometry: Application to measurement by Active Neutron Interrogation

International Nuclear Information System (INIS)

Baudry, G.

2003-11-01

In the field of the measurement of low masses of fissile material ( 235 U, 239 Pu, 241 Pu) in radioactive waste drums, the Active Neutron Interrogation is a non-destructive method achieving good results. It does however remain reliant upon uncertainties related to the matrix effects on interrogation and fission neutrons. The aim of this thesis is to develop a correction method able to take into account these matrix effects by quantifying the amount of absorbent materials (chlorine and hydrogen) in a 118- liter homogeneous matrix. The main idea is to use the gamma-ray spectrometry of gamma emitted by neutron captures to identify and quantify the composition of the matrix. An indicator from its chlorine content is then deduced in order to choose the calibration coefficient which best represents the real composition of the matrix. This document firstly presents the needs of control and characterization of radioactive objects, and the means used in the field of nuclear measurement. Emphases is put in particular on the Active Neutron Interrogation method. The matrices of interest are those made of light technological waste (density ≤ 0,4 g/cm 3 ) containing hydrogenated and chlorinated materials. The advantages of gamma-rays emitted by neutron captures for the determination of a chlorine content indicator of the matrices and the principles of the correction method are then explained. Measurements have been firstly realized with an existing Neutron Interrogation device (PROMETHEE 6). Such measurements have proven its inadequacy: no signal from the matrix hydrogen was detected, due to an intense signal from the polyethylene contained in some cell elements. Moreover, the matrix chlorine content appeared difficult to be measured. A new and specific device, named REGAIN and dedicated to active gamma-rays spectrometry, was defined with the Monte-Carlo N-Particle (MCNP) code. The experiments conducted with this new device made it possible to detect the hydrogen from the

Resveratrol increases nucleus pulposus matrix synthesis through activating the PI3K/Akt signaling pathway under mechanical compression in a disc organ culture.

Science.gov (United States)

Han, Xiaorui; Leng, Xiaoming; Zhao, Man; Wu, Mei; Chen, Amei; Hong, Guoju; Sun, Ping

2017-12-22

Disc nucleus pulposus (NP) matrix homeostasis is important for normal disc function. Mechanical overloading seriously decreases matrix synthesis and increases matrix degradation. The present study aims to investigate the effects of resveratrol on disc NP matrix homeostasis under a relatively high-magnitude mechanical compression and the potential mechanism underlying this process. Porcine discs were perfusion-cultured and subjected to a relatively high-magnitude mechanical compression (1.3 MPa at a frequency of 1.0 Hz for 2 h once per day) for 7 days in a mechanically active bioreactor. The non-compressed discs were used as controls. Resveratrol was added along with culture medium to observe the effects of resveratrol on NP matrix synthesis under mechanical load respectively. NP matrix synthesis was evaluated by histology, biochemical content (glycosaminoglycan (GAG) and hydroxyproline (HYP)), and expression of matrix macromolecules (aggrecan and collagen II). Results showed that this high-magnitude mechanical compression significantly decreased NP matrix content, indicated by the decreased staining intensity of Alcian Blue and biochemical content (GAG and HYP), and the down-regulated expression of NP matrix macromolecules (aggrecan and collagen II). Further analysis indicated that resveratrol partly stimulated NP matrix synthesis and increased activity of the PI3K/Akt pathway in a dose-dependent manner under mechanical compression. Together, resveratrol is beneficial for disc NP matrix synthesis under mechanical overloading, and the activation of the PI3K/Akt pathway may participate in this regulatory process. Resveratrol may be promising to regenerate mechanical overloading-induced disc degeneration. © 2017 The Author(s).

The effect of tomatine on metastasis related matrix metalloproteinase (MMP) activities in breast cancer cell model.

Science.gov (United States)

Yelken, Besra Özmen; Balcı, Tuğçe; Süslüer, Sunde Yılmaz; Kayabaşı, Çağla; Avcı, Çığır Biray; Kırmızıbayrak, Petek Ballar; Gündüz, Cumhur

2017-09-05

Breast cancer is one of the most common malignancies in women and metastasis is the cause of morbidity and mortality in patients. In the development of metastasis, the matrix metalloproteinase (MMP) family has a very important role in tumor development. MMP-2 and MMP-9 work together for extracellular matrix (ECM) cleavage to increase migration. Tomatine is a secondary metabolite that has a natural defense role against plants, fungi, viruses and bacteria that are synthesized from tomato. In additıon, tomatine is also known that it breaks down the cell membrane and is a strong inhibitor in human cancer cells. In this study, it was aimed to evaluate the effect of tomatine on cytotoxicity, apoptosis and matrix metalloproteinase inhibition in MCF-7 cell lines. Human breast cancer cell line (MCF-7) was used as a cell line. In MCF-7 cells, the IC 50 dose of tomatine was determined to be 7.07μM. According to the control cells, apoptosis increased 3.4 fold in 48thh. Activation of MMP-2, MMP-9 and MMP-9\\NGAL has been shown to decrease significantly in cells treated with tomatine by gelatin zymography compared to the control. As a result, matrix metalloproteinase activity and cell proliferation were suppressed by tomatine and this may provide support in treatment methods. Copyright © 2017 Elsevier B.V. All rights reserved.

Preferential binding of DNA primase to the nuclear matrix

International Nuclear Information System (INIS)

Wood, S.H.; Collins, J.M.

1986-01-01

Several lines of research have stimulated interest in the nuclear matrix as the subcellular site of DNA replication. The authors have recently reported a relationship between rates of DNA synthesis and the differential binding of polymerase α to the nuclear matrix. They now report the detection of DNA primase bound to the HeLa nuclear matrix. Matrix-bound primase can be measured either indirectly, by the incorporation of [ 32 P] dAMP into an unprimed single-stranded template, or directly, by the incorporation of [ 3 H] AMP into matrix DNA. Characteristics of this system include a requirement for ATP, inhibition by adenosine-5'-0-(3'-thiotriphosphate), a primase inhibitor, and insensitivity to aphidicolin and α-amanitine, inhibitors of polymerase α and RNA polymerase, respectively. Subcellular quantification of primase and polymerase α activity revealed that while a majority of primase activity is bound to the matrix (72%), only 32% of polymerase α activity is matrix-bound. Treatment of the nuclear matrix with β-D-Octylglucoside allowed the solubilization of 54% of primase activity and 39% of polymerase α activity. This data provides further evidence of a structural and functional role for the nuclear matrix in DNA replication. The ability to solubilize matrix-bound replicative enzymes may prove to be an important tool in the elucidation of the spatial organization of DNA replication

Integrins and extracellular matrix in mechanotransduction

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Ramage L

2011-12-01

Full Text Available Lindsay RamageQueen’s Medical Research Institute, University of Edinburgh, Edinburgh, UKAbstract: Integrins are a family of cell surface receptors which mediate cell–matrix and cell–cell adhesions. Among other functions they provide an important mechanical link between the cells external and intracellular environments while the adhesions that they form also have critical roles in cellular signal-transduction. Cell–matrix contacts occur at zones in the cell surface where adhesion receptors cluster and when activated the receptors bind to ligands in the extracellular matrix. The extracellular matrix surrounds the cells of tissues and forms the structural support of tissue which is particularly important in connective tissues. Cells attach to the extracellular matrix through specific cell-surface receptors and molecules including integrins and transmembrane proteoglycans. Integrins work alongside other proteins such as cadherins, immunoglobulin superfamily cell adhesion molecules, selectins, and syndecans to mediate cell–cell and cell–matrix interactions and communication. Activation of adhesion receptors triggers the formation of matrix contacts in which bound matrix components, adhesion receptors, and associated intracellular cytoskeletal and signaling molecules form large functional, localized multiprotein complexes. Cell–matrix contacts are important in a variety of different cell and tissue properties including embryonic development, inflammatory responses, wound healing, and adult tissue homeostasis. This review summarizes the roles and functions of integrins and extracellular matrix proteins in mechanotransduction.Keywords: ligand binding, α subunit, ß subunit, focal adhesion, cell differentiation, mechanical loading, cell–matrix interaction

Vibrationally specific photoionization cross sections of acrolein leading to the Χ{sup ~}A{sup '} ionic state

Energy Technology Data Exchange (ETDEWEB)

López-Domínguez, Jesús A.; Lucchese, Robert R., E-mail: lucchese@mail.chem.tamu.edu [Department of Chemistry, Texas A and M University, College Station, Texas 77843-3255 (United States); Fulfer, K. D.; Hardy, David; Poliakoff, E. D. [Department of Chemistry, Louisiana State University, Baton Rouge, Louisiana 70803 (United States); Aguilar, A. A. [Advanced Light Source, Lawrence Berkeley National Laboratory, University of California, Berkeley, California 94720 (United States)

2014-09-07

The vibrational branching ratios in the photoionization of acrolein for ionization leading to the Χ{sup ~}A{sup '} ion state were studied. Computed logarithmic derivatives of the cross section and the corresponding experimental data derived from measured vibrational branching ratios for several normal modes (ν{sub 9}, ν{sub 10}, ν{sub 11}, and ν{sub 12}) were found to be in relatively good agreement, particularly for the lower half of the 11–100 eV photon energy range considered. Two shape resonances have been found near photon energies of 15.5 and 23 eV in the photoionization cross section and have been demonstrated to originate from the partial cross section of the A{sup ′} scattering symmetry. The wave functions computed at the resonance complex energies are delocalized over the whole molecule. By looking at the dependence of the cross section on the different normal mode displacements together with the wave function at the resonant energy, a qualitative explanation is given for the change of the cross sections with respect to changing geometry.

Matrix Metalloproteinase Enzyme Family

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Ozlem Goruroglu Ozturk

2013-04-01

Full Text Available Matrix metalloproteinases play an important role in many biological processes such as embriogenesis, tissue remodeling, wound healing, and angiogenesis, and in some pathological conditions such as atherosclerosis, arthritis and cancer. Currently, 24 genes have been identified in humans that encode different groups of matrix metalloproteinase enzymes. This review discuss the members of the matrix metalloproteinase family and their substrate specificity, structure, function and the regulation of their enzyme activity by tissue inhibitors. [Archives Medical Review Journal 2013; 22(2.000: 209-220

Omega-3 and Omega-6 Fatty Acids Act as Inhibitors of the Matrix Metalloproteinase-2 and Matrix Metalloproteinase-9 Activity.

Science.gov (United States)

Nicolai, Eleonora; Sinibaldi, Federica; Sannino, Gianpaolo; Laganà, Giuseppina; Basoli, Francesco; Licoccia, Silvia; Cozza, Paola; Santucci, Roberto; Piro, Maria Cristina

2017-08-01

Polyunsaturated fatty acids have been reported to play a protective role in a wide range of diseases characterized by an increased metalloproteinases (MMPs) activity. The recent finding that omega-3 and omega-6 fatty acids exert an anti-inflammatory effect in periodontal diseases has stimulated the present study, designed to determine whether such properties derive from a direct inhibitory action of these compounds on the activity of MMPs. To this issue, we investigated the effect exerted by omega-3 and omega-6 fatty acids on the activity of MMP-2 and MMP-9, two enzymes that actively participate to the destruction of the organic matrix of dentin following demineralization operated by bacteria acids. Data obtained (both in vitro and on ex-vivo teeth) reveal that omega-3 and omega-6 fatty acids inhibit the proteolytic activity of MMP-2 and MMP-9, two enzymes present in dentin. This observation is of interest since it assigns to these compounds a key role as MMPs inhibitors, and stimulates further study to better define their therapeutic potentialities in carious decay.

Efficiency criterion for teleportation via channel matrix, measurement matrix and collapsed matrix

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Xin-Wei Zha

Full Text Available In this paper, three kinds of coefficient matrixes (channel matrix, measurement matrix, collapsed matrix associated with the pure state for teleportation are presented, the general relation among channel matrix, measurement matrix and collapsed matrix is obtained. In addition, a criterion for judging whether a state can be teleported successfully is given, depending on the relation between the number of parameter of an unknown state and the rank of the collapsed matrix. Keywords: Channel matrix, Measurement matrix, Collapsed matrix, Teleportation

Active matrix metalloproteases are expressed early on and are high during the Barrett's esophagus malignancy sequence

NARCIS (Netherlands)

Davelaar, Akueni L.; Straub, Daniëlle; Buttar, Navtej S.; Fockens, Paul; Krishnadath, Kausilia K.

2015-01-01

Objective. Molecular processes underlying Barrett's malignant development are poorly understood. Matrix metalloproteases (MMPs) are enzymes involved in inflammation, tissue remodeling, and malignant development. Therefore, active MMPs may have a role in early metaplasia development and Barrett's

Tissue- and Cell-Specific Co-localization of Intracellular Gelatinolytic Activity and Matrix Metalloproteinase 2

Science.gov (United States)

Solli, Ann Iren; Fadnes, Bodil; Winberg, Jan-Olof; Uhlin-Hansen, Lars

2013-01-01

Matrix metalloproteinase 2 (MMP-2) is a proteolytic enzyme that degrades extracellular matrix proteins. Recent studies indicate that MMP-2 also has a role in intracellular proteolysis during various pathological conditions, such as ischemic injuries in heart and brain and in tumor growth. The present study was performed to map the distribution of intracellular MMP-2 activity in various mouse tissues and cells under physiological conditions. Samples from normal brain, heart, lung, liver, spleen, pancreas, kidney, adrenal gland, thyroid gland, gonads, oral mucosa, salivary glands, esophagus, intestines, and skin were subjected to high-resolution in situ gelatin zymography and immunohistochemical staining. In hepatocytes, cardiac myocytes, kidney tubuli cells, epithelial cells in the oral mucosa as well as in excretory ducts of salivary glands, and adrenal cortical cells, we found strong intracellular gelatinolytic activity that was significantly reduced by the metalloprotease inhibitor EDTA but not by the cysteine protease inhibitor E-64. Furthermore, the gelatinolytic activity was co-localized with MMP-2. Western blotting and electron microscopy combined with immunogold labeling revealed the presence of MMP-2 in different intracellular compartments of isolated hepatocytes. Our results indicate that MMP-2 takes part in intracellular proteolysis in specific tissues and cells during physiological conditions. PMID:23482328

Atmospheric-Pressure Cold Plasmas Used to Embed Bioactive Compounds in Matrix Material for Active Packaging of Fruits and Vegetables

Science.gov (United States)

Fernandez, Sulmer; Pedrow, Patrick; Powers, Joseph; Pitts, Marvin

2009-10-01

Active thin film packaging is a technology with the potential to provide consumers with new fruit and vegetable products-if the film can be applied without deactivating bioactive compounds.Atmospheric pressure cold plasma (APCP) processing can be used to activate monomer with concomitant deposition of an organic plasma polymerized matrix material and to immobilize a bioactive compound all at or below room temperature.Aims of this work include: 1) immobilize an antimicrobial in the matrix; 2) determine if the antimicrobial retains its functionality and 3) optimize the reactor design.The plasma zone will be obtained by increasing the voltage on an electrode structure until the electric field in the feed material (argon + monomer) yields electron avalanches. Results will be described using Red Delicious apples.Prospective matrix precursors are vanillin and cinnamic acid.A prospective bioactive compound is benzoic acid.

Buddleja officinalis inhibits high glucose-induced matrix metalloproteinase activity in human umbilical vein endothelial cells.

Science.gov (United States)

Lee, Yun Jung; Kang, Dae Gill; Kim, Jin Sook; Lee, Ho Sub

2008-12-01

The aim of the present investigation was to investigate whether an aqueous extract of Buddleja officinalis (ABO), a traditional Korean herbal medicine, suppresses the endothelial extracellular matrix degradation under high glucose condition. The incubation with high concentration of glucose (25 mM) increased significantly matrix metalloproteinase (MMP)-2/-9 expressions and activities in primary cultured human umbilical vein endothelial cells (HUVEC). Pretreatment with ABO decreased high glucose-induced increase of MMP-2/-9 activities in a dose-dependent manner. Real time qRT-PCR revealed that high glucose-induced MMP-2/-9 mRNA expression levels were attenuated by pretreatment with ABO. High glucose-induced MCP-1 and IL-8 mRNA expression levels also decreased by ABO. ABO decreased high glucose-induced hydrogen peroxide production, oxidative stress marker. These results provide new insights into the pathophysiological mechanisms for anti-inflammatory properties of ABO in vascular diseases associated with diabetes mellitus. (c) 2008 John Wiley & Sons, Ltd.

Large-Area High-Performance Flexible Pressure Sensor with Carbon Nanotube Active Matrix for Electronic Skin.

Science.gov (United States)

Nela, Luca; Tang, Jianshi; Cao, Qing; Tulevski, George; Han, Shu-Jen

2018-03-14

Artificial "electronic skin" is of great interest for mimicking the functionality of human skin, such as tactile pressure sensing. Several important performance metrics include mechanical flexibility, operation voltage, sensitivity, and accuracy, as well as response speed. In this Letter, we demonstrate a large-area high-performance flexible pressure sensor built on an active matrix of 16 × 16 carbon nanotube thin-film transistors (CNT TFTs). Made from highly purified solution tubes, the active matrix exhibits superior flexible TFT performance with high mobility and large current density, along with a high device yield of nearly 99% over 4 inch sample area. The fully integrated flexible pressure sensor operates within a small voltage range of 3 V and shows superb performance featuring high spatial resolution of 4 mm, faster response than human skin (<30 ms), and excellent accuracy in sensing complex objects on both flat and curved surfaces. This work may pave the road for future integration of high-performance electronic skin in smart robotics and prosthetic solutions.

Photorefractive keratectomy: measuring the matrix metalloproteinase activity and chondroitin sulfate concentration in tear fluid

Directory of Open Access Journals (Sweden)

Tetsuya Mutoh

2010-09-01

Full Text Available Tetsuya Mutoh, Masaya Nishio, Yukihiro Matsumoto, Kiyomi Arai, Makoto ChikudaDepartment of Ophthalmology, Dokkyo Medical University Koshigaya Hospital, Saitama, JapanAbstract: We herein report the case of a 20-year-old man who underwent a photorefractive keratectomy (PRK. We measured matrix metalloproteinase-9 (MMP-9 activity and chondroitin 4 sulfate and chondroitin 6 sulfate concentrations in tear fluid. Tear fluid was collected preoperatively via microcapillary tube, and was collected postoperatively on the first and fourth days, and after one week, one month, three months, and six months. Samples were formulated by dilution with 200 µL of saline. MMP-9 activity was analyzed by an enzyme immunocapture activity assay, and the concentrations of chondroitin sulfate were analyzed by enzyme-linked immunosorbent assay. No complications were observed after surgery, except for a minimal subepithelial haze. Although MMP-9 activity changed on the fourth postoperative day, the activity changed only minimally at this time. Chondroitin 4 sulfate concentrations in tear fluid increased dramatically from one week to one month, decreased transiently at three months, and increased by six months. The chondroitin 6 sulfate concentration did not normalize within one week, and decreased from one week to three months compared with the preoperative score, and was close to the preoperative score at six months. We conclude that corneal wound healing was still incomplete six months after PRK, and chondroitin 4 sulfate appears to be critical in this process.Keywords: matrix metalloproteinase, chondroitin sulfate, human tear fluid, photorefractive keratectomy, corneal wound healing

Respiratory Effects and Systemic Stress Response Following ...

Science.gov (United States)

Previous studies have demonstrated that exposure to the pulmonary irritant ozone causes myriad systemic metabolic and pulmonary effects attributed to sympathetic and hypothalamus-pituitary-adrenal (HPA) axis activation, which are exacerbated in metabolically impaired models. We examined respiratory and systemic effects following exposure to a sensory irritant acrolein to elucidate the systemic and pulmonary consequences in healthy and diabetic rat models. Male Wistar and Goto Kakizaki (GK) rats, a nonobese type II diabetic Wistar-derived model, were exposed by inhalation to 0, 2, or 4 ppm acrolein, 4 h/d for 1 or 2 days. Exposure at 4 ppm significantly increased pulmonary and nasal inflammation in both strains with vascular protein leakage occurring only in the nose. Acrolein exposure (4 ppm) also caused metabolic impairment by inducing hyperglycemia and glucose intolerance (GK > Wistar). Serum total cholesterol (GKs only), low-density lipoprotein (LDL) cholesterol (both strains), and free fatty acids (GK > Wistar) levels increased; however, no acrolein-induced changes were noted in branched-chain amino acid or insulin levels. These responses corresponded with a significant increase in corticosterone and modest but insignificant increases in adrenaline in both strains, suggesting activation of the HPA axis. Collectively, these data demonstrate that acrolein exposure has a profound effect on nasal and pulmonary inflammation, as well as glucose and lipid metabolis

Ulex europaeus I lectin induces activation of matrix-metalloproteinase-2 in endothelial cells.

Science.gov (United States)

Gomez, D E; Yoshiji, H; Kim, J C; Thorgeirsson, U P

1995-11-02

In this report, we show that the lectin Ulex europaeus agglutinin I (UEA I), which binds to alpha-linked fucose residues on the surface of endothelial cells, mediates activation of the 72-kDa matrix metalloproteinase-2 (MMP-2). A dose-dependent increase in the active 62-kDa form of MMP-2 was observed in conditioned medium from monkey aortic endothelial cells (MAEC) following incubation with concentrations of UEA I ranging from 2 to 100 micrograms/ml. The increase in the 62-kDa MMP-2 gelatinolytic activity was not reflected by a rise in MMP-2 gene expression. The UEA I-mediated activation of MMP-2 was blocked by L-fucose, which competes with UEA I for binding to alpha-fucose. These findings may suggest that a similar in vivo mechanism exists, whereby adhesive interactions between tumor cell lectins and endothelial cells can mediate MMP-2 activation.

Atypical protein kinase C activity is required for extracellular matrix degradation and invasion by Src-transformed cells.

Science.gov (United States)

Rodriguez, Elena M; Dunham, Elizabeth E; Martin, G Steven

2009-10-01

Atypical protein kinase C (aPKC) isoforms have been shown to mediate Src-dependent signaling in response to growth factor stimulation. To determine if aPKC activity contributes to the transformed phenotype of cells expressing oncogenic Src, we have examined the activity and function of aPKCs in 3T3 cells expressing viral Src (v-Src). aPKC activity and tyrosine phosphorylation were found to be elevated in some but not all clones of mouse fibroblasts expressing v-Src. aPKC activity was inhibited either by addition of a membrane-permeable pseudosubstrate, by expression of a dominant-negative aPKC, or by RNAi-mediated knockdown of specific aPKC isoforms. aPKC activity contributes to morphological transformation and stress fiber disruption, and is required for migration of Src-transformed cells and for their ability to polarize at the edge of a monolayer. The lambda isoform of aPKC is specifically required for invasion through extracellular matrix in Boyden chamber assays and for degradation of the extracellular matrix in in situ zymography assays. Tyrosine phosphorylation of aPKClambda is required for its ability to promote cell invasion. The defect in invasion upon aPKC inhibition appears to result from a defect in the assembly and/or function of podosomes, invasive adhesions on the ventral surface of the cell that are sites of protease secretion. aPKC was also found to localize to podosomes of v-Src transformed cells, suggesting a direct role for aPKC in podosome assembly and/or function. We conclude that basal or elevated aPKC activity is required for the ability of Src-transformed cells to degrade and invade the extracellular matrix. Copyright 2009 Wiley-Liss, Inc.

Matrix Metalloproteinase Activity in Infections by an Encephalitic Virus, Mouse Adenovirus Type 1

Science.gov (United States)

Ashley, Shanna L.; Pretto, Carla D.; Stier, Matthew T.; Kadiyala, Padma; Castro-Jorge, Luiza; Hsu, Tien-Huei; Doherty, Robert; Carnahan, Kelly E.; Castro, Maria G.; Lowenstein, Pedro R.

2017-01-01

ABSTRACT Mouse adenovirus type 1 (MAV-1) infection causes encephalitis in susceptible strains of mice and alters the permeability of infected brains to small molecules, which indicates disruption of the blood-brain barrier (BBB). Under pathological conditions, matrix metalloproteinases (MMPs) can disrupt the BBB through their proteolytic activity on basement membrane and tight junction proteins. We examined whether MAV-1 infection alters MMP activity in vivo and in vitro. Infected MAV-1-susceptible SJL mice had higher MMP2 and MMP9 activity in brains, measured by gelatin zymography, than mock-infected mice. Infected MAV-1-resistant BALB/c mice had MMP activity levels equivalent to those in mock infection. Primary SJL mouse brain endothelial cells (a target of MAV-1 in vivo) infected ex vivo with MAV-1 had no difference in activities of secreted MMP2 and MMP9 from mock cells. We show for the first time that astrocytes and microglia are also infected in vivo by MAV-1. Infected mixed primary cultures of astrocytes and microglia had higher levels of MMP2 and MMP9 activity than mock-infected cells. These results indicate that increased MMP activity in the brains of MAV-1-infected susceptible mice may be due to MMP activity produced by endothelial cells, astrocytes, and microglia, which in turn may contribute to BBB disruption and encephalitis in susceptible mice. IMPORTANCE RNA and DNA viruses can cause encephalitis; in some cases, this is accompanied by MMP-mediated disruption of the BBB. Activated MMPs degrade extracellular matrix and cleave tight-junction proteins and cytokines, modulating their functions. MAV-1 infection of susceptible mice is a tractable small-animal model for encephalitis, and the virus causes disruption of the BBB. We showed that MAV-1 infection increases enzymatic activity of two key MMPs known to be secreted and activated in neuroinflammation, MMP2 and MMP9, in brains of susceptible mice. MAV-1 infects endothelial cells, astrocytes, and

Neutron activation of chlorine in zirconium and zirconium alloys use of the matrix as comparator

International Nuclear Information System (INIS)

Cohen, I.M.; Gomez, C.D.; Mila, M.I.

1981-01-01

A procedure is described for neutron activation analysis of chlorine in zirconium and zirconium alloys. Calculation of chlorine concentration is performed relative to zirconium concentration in the matrix in order to minimize effects of differences in irradiation and counting geometry. Principles of the method and the results obtained are discussed. (author)

Food matrix and processing influence on carotenoid bioaccessibility and lipophilic antioxidant activity of fruit juice-based beverages.

Science.gov (United States)

Rodríguez-Roque, María Janeth; de Ancos, Begoña; Sánchez-Vega, Rogelio; Sánchez-Moreno, Concepción; Cano, M Pilar; Elez-Martínez, Pedro; Martín-Belloso, Olga

2016-01-01

The biological activity of carotenoids depends on their bioaccessibility and solubilization in the gastrointestinal tract. These compounds are poorly dispersed in the aqueous media of the digestive tract due to their lipophilic nature. Thus, it is important to analyze the extent to which some factors, such as the food matrix and food processing, may improve their bioaccessibility. Beverages formulated with a blend of fruit juices and water (WB), milk (MB) or soymilk (SB) were treated by high-intensity pulsed electric fields (HIPEF) (35 kV cm(-1) with 4 μs bipolar pulses at 200 Hz for 1800 μs), high-pressure processing (HPP) (400 MPa at 40 °C for 5 min) or thermal treatment (TT) (90 °C for 1 min) in order to evaluate the influence of food matrix and processing on the bioaccessibility of carotenoids and on the lipophilic antioxidant activity (LAA). The bioaccessibility of these compounds diminished after applying any treatment (HIPEF, HPP and TT), with the exception of cis-violaxanthin + neoxanthin, which increased by 79% in HIPEF and HPP beverages. The lowest carotenoid bioaccessibility was always obtained in TT beverages (losses up to 63%). MB was the best food matrix for improving the bioaccessibility of carotenoids, as well as the LAA. The results demonstrate that treatment and food matrix modulated the bioaccessibility of carotenoids as well as the lipophilic antioxidant potential of beverages. Additionally, HIPEF and HPP could be considered as promising technologies to obtain highly nutritional and functional beverages.

Immobilization of cellulase using porous polymer matrix

International Nuclear Information System (INIS)

Kumakura, M.; Kaetsu, I.

1984-01-01

A new method is discussed for the immobilization of cellulase using porous polymer matrices, which were obtained by radiation polymerization of hydrophilic monomers. In this method, the immobilized enzyme matrix was prepared by enzyme absorbtion in the porous polymer matrix and drying treatment. The enzyme activity of the immobilized enzyme matrix varied with monomer concentration, cooling rate of the monomer solution, and hydrophilicity of the polymer matrix, takinn the change of the nature of the porous structure in the polymer matrix. The leakage of the enzymes from the polymer matrix was not observed in the repeated batch enzyme reactions

How to get the Matrix Organization to Work

DEFF Research Database (Denmark)

Burton, Richard M.; Obel, Børge; Håkonsson, Dorthe Døjbak

2015-01-01

a matrix to work, taking a multi-contingency perspective. We translate the matrix concept for designers and managers who are considering a matrix organization and argue that three factors are critical for its success: (1) Strong purpose: Only choose the matrix structure if there are strong reasons...... for doing so, (2) Alignment among contingencies: A matrix can only be successful if key contingencies are aligned with the matrix’s purpose, and (3) Management of junctions: The success of a matrix depends on how well activities at the junctions of the matrix are managed....

Matrix Metalloproteinases in Non-Neoplastic Disorders

Science.gov (United States)

Tokito, Akinori; Jougasaki, Michihisa

2016-01-01

The matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases belonging to the metzincin superfamily. There are at least 23 members of MMPs ever reported in human, and they and their substrates are widely expressed in many tissues. Recent growing evidence has established that MMP not only can degrade a variety of components of extracellular matrix, but also can cleave and activate various non-matrix proteins, including cytokines, chemokines and growth factors, contributing to both physiological and pathological processes. In normal conditions, MMP expression and activity are tightly regulated via interactions between their activators and inhibitors. Imbalance among these factors, however, results in dysregulated MMP activity, which causes tissue destruction and functional alteration or local inflammation, leading to the development of diverse diseases, such as cardiovascular disease, arthritis, neurodegenerative disease, as well as cancer. This article focuses on the accumulated evidence supporting a wide range of roles of MMPs in various non-neoplastic diseases and provides an outlook on the therapeutic potential of inhibiting MMP action. PMID:27455234

Effect Of Neutron Activation Factor On The Physico-Chemical Properties Of Hydrophilic And Hydrophobic Polymer Formulation Of Matrix Tablets

International Nuclear Information System (INIS)

Ibrahim Ijang; Bohari Yaacob; Nordiana, N.R.

2011-01-01

This study was to investigate effect of neutron activation on the physicochemical properties and in vitro dissolution of sustained-release matrix tablets. The tablets incorporation of Samarium oxide (Sm 2 O 3 ) and were compared before and after irradiation with thermal neutron for 5 minutes at 1.2 x 10 12 neutron cm -2 s -1 . The neutron activation factor did not influence the compression properties of the tablets. The dissolution tests showed that irradiation increased the release of the model drug ketoprofen from the tablets. This effect might be explained by polymer degradation. Incorporation of Sm 2 O 3 in the matrix tablets did not influence the release. (author)

Respiratory Effects and Systemic Stress Response Following ...

Science.gov (United States)

Previous studies have demonstrated that exposure to ozone, a pulmonary irritant, causes myriad systemic metabolic and pulmonary effects that are attributed to neuronal and hypothalamus-pituitary-adrenal (HPA) axis activation, which are exacerbated in metabolically-impaired models. In order to elucidate the systemic consequences and the contribution of the HPA axis in mediating metabolic and respiratory effects of acrolein, a sensory irritant, we examined pulmonary, nasal, and systemic effects in rats following exposure. Male, 10 week old Wistar and Goto Kakizaki (GK) rats, a non-obese type II diabetic Wistar-derived model, were exposed to 0, 2 or 4 ppm acrolein, 4h/day for 1 or 2 days. Acrolein exposure at 4 ppm significantly increased pulmonary and nasal damage in both strains as demonstrated by increased inspiratory and expiratory times indicating labored breathing, elevated biomarkers of injury, and neutrophilic inflammation. Overall, at both time points acrolein exposure caused noticeably more damage in the nasal passages as opposed to the lung with vascular protein leakage occurring only in the nose. Acrolein exposure (4 ppm) also led to metabolic impairment by inducing hyperglycemia and glucose intolerance (GK>Wistar) as indicated by glucose tolerance testing. In addition, serum total cholesterol (GKs only), LDL cholesterol (both strains), and free fatty acids (GK>Wistar) levels increased; however, no acrolein-induced changes were noted in branched-c

Curcumin influences hepatic expression patterns of matrix metalloproteinases in liver toxicity.

Science.gov (United States)

Rukkumani, Rajagopalan; Aruna, Kode; Varma, Penumathsa Suresh; Menon, Venugopal Padmanabhan

2004-07-01

Hepatic fibrosis is a result of an imbalance between enhanced matrix synthesis and diminished breakdown of connective tissue proteins, the net result of which is increased deposition of Extra Cellular Matrix. In this concept Matrix Metalloproteinases play an important role because their activity is largely responsible for extra cellular matrix breakdown. In the present study we have tested the influence of curcumin, the active principle of turmeric, on matrix metalloproteinase expression during alcohol and thermally oxidised sunflower oil induced liver toxicity. Male albino Wistar rats were used for the study. The matrix metalloproteinase expressions were found to be increased significantly in alcohol as well as thermally oxidised sunflower oil groups and on treatment with curcumin there was a significant decrease. In alcohol + thermally oxidised sunflower oil group, we found a significant decrease in matrix metalloproteinase activities. Administration of curcumin significantly improved their activities. From the results obtained, we could conclude that curcumin influences the hepatic matrix metalloproteinases and effectively protects liver against alcohol and delta PUFA induced toxicity.

Strategy BMT Al-Ittihad Using Matrix IE, Matrix SWOT 8K, Matrix SPACE and Matrix TWOS

Directory of Open Access Journals (Sweden)

Nofrizal Nofrizal

2018-03-01

Full Text Available This research aims to formulate and select BMT Al-Ittihad Rumbai strategy to face the changing of business environment both from internal environment such as organization resources, finance, member and external business such as competitor, economy, politics and others. This research method used Analysis of EFAS, IFAS, IE Matrix, SWOT-8K Matrix, SPACE Matrix and TWOS Matrix. our hope from this research it can assist BMT Al-Ittihad in formulating and selecting strategies for the sustainability of BMT Al-Ittihad in the future. The sample in this research is using purposive sampling technique that is the manager and leader of BMT Al-IttihadRumbaiPekanbaru. The result of this research shows that the position of BMT Al-Ittihad using IE Matrix, SWOT-8K Matrix and SPACE Matrix is in growth position, stabilization and aggressive. The choice of strategy after using TWOS Matrix is market penetration, market development, vertical integration, horizontal integration, and stabilization (careful.

Peroxisome proliferator-activated receptor δ inhibits Porphyromonas gingivalis lipopolysaccharide-induced activation of matrix metalloproteinase-2 by downregulating NADPH oxidase 4 in human gingival fibroblasts.

Science.gov (United States)

Yoo, T; Ham, S A; Hwang, J S; Lee, W J; Paek, K S; Oh, J W; Kim, J H; Do, J T; Han, C W; Kim, J H; Seo, H G

2016-10-01

We investigated the roles of peroxisome proliferator-activated receptor δ (PPARδ) in Porphyromonas gingivalis-derived lipopolysaccharide (Pg-LPS)-induced activation of matrix metalloproteinase 2 (MMP-2). In human gingival fibroblasts (HGFs), activation of PPARδ by GW501516, a specific ligand of PPARδ, inhibited Pg-LPS-induced activation of MMP-2 and generation of reactive oxygen species (ROS), which was associated with reduced expression of NADPH oxidase 4 (Nox4). These effects were significantly smaller in the presence of small interfering RNA targeting PPARδ or the specific PPARδ inhibitor GSK0660, indicating that PPARδ is involved in these events. In addition, modulation of Nox4 expression by small interfering RNA influenced the effect of PPARδ on MMP-2 activity, suggesting a mechanism in which Nox4-derived ROS modulates MMP-2 activity. Furthermore, c-Jun N-terminal kinase and p38, but not extracellular signal-regulated kinase, mediated PPARδ-dependent inhibition of MMP-2 activity in HGFs treated with Pg-LPS. Concomitantly, PPARδ-mediated inhibition of MMP-2 activity was associated with the restoration of types I and III collagen to levels approaching those in HGFs not treated with Pg-LPS. These results indicate that PPARδ-mediated downregulation of Nox4 modulates cellular redox status, which in turn plays a critical role in extracellular matrix homeostasis through ROS-dependent regulation of MMP-2 activity. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

MT1-MMP promotes cell growth and ERK activation through c-Src and paxillin in three-dimensional collagen matrix

International Nuclear Information System (INIS)

Takino, Takahisa; Tsuge, Hisashi; Ozawa, Terumasa; Sato, Hiroshi

2010-01-01

Membrane-type 1 matrix metalloproteinase (MT1-MMP) is essential for tumor invasion and growth. We show here that MT1-MMP induces extracellular signal-regulated kinase (ERK) activation in cancer cells cultured in collagen gel, which is indispensable for their proliferation. Inhibition of MT1-MMP by MMP inhibitor or small interfering RNA suppressed activation of focal adhesion kinase (FAK) and ERK in MT1-MMP-expressing cancer cells, which resulted in up-regulation of p21 WAF1 and suppression of cell growth in collagen gel. Cell proliferation was also abrogated by the inhibitor against ERK pathway without affecting FAK phosphorylation. MT1-MMP and integrin α v β 3 were shown to be involved in c-Src activation, which induced FAK and ERK activation in collagen gel. These MT1-MMP-mediated signal transductions were paxillin dependent, as knockdown of paxillin reduced cell growth and ERK activation, and co-expression of MT1-MMP with paxillin induced ERK activation. The results suggest that MT1-MMP contributes to proliferation of cancer cells in the extracellular matrix by activating ERK through c-Src and paxillin.

Optical Imaging of Matrix Metalloproteinase-7 Activity in Vivo Using a Proteolytic Nanobeacon

Directory of Open Access Journals (Sweden)

Randy L. Scherer

2008-05-01

Full Text Available Matrix metalloproteinases (MMPs are extracellular proteolytic enzymes involved in tumor progression. We present the in vivo detection and quantitation of MMP7 activity using a specific near-infrared polymer-based proteolytic beacon, PB-M7NIR. PB-M7NIR is a pegylated polyamidoamine PAMAM-Generation 4 dendrimer core covalently coupled to a Cy5.5-labeled peptide representing a selective substrate that monitors MMP7 activity (sensor and AF750 as an internal reference to monitor relative substrate concentration (reference. In vivo imaging of tumors expressing MMP7 had a median sensor to reference ratio 2.2-fold higher than a that of a bilateral control tumor. Ex vivo imaging of intestines of multiple intestinal neoplasia (APCMin mice injected systemically with PB-M7NIR revealed a sixfold increase in the sensor to reference ratio in the adenomas of APCMin mice compared with control intestinal tissue or adenomas from MMP7-null Min mice. PB-M7NIR detected tumor sizes as small as 0.01 cm2, and the sensor to reference ratio was independent of tumor size. Histologic sectioning of xenograft tumors localized the proteolytic signal to the extracellular matrix; MMP7-overexpressing tumors displayed an approximately 300-fold enhancement in the sensor to reference ratio compared with nonexpressing tumor cells. In APCMin adenomas, the proteolytic signal colocalized with the endogenously expressed MMP7 protein, with sensor to reference ratios approximately sixfold greater than that of normal intestinal epithelium. PB-M7NIR provides a useful reagent for the in vivo and ex vivo quantitation and localization of MMP-selective proteolytic activity.

A novel assay for extracellular matrix remodeling associated with liver fibrosis

DEFF Research Database (Denmark)

Barascuk, N; Veidal, S S; Larsen, L

2010-01-01

Accumulation of extracellular matrix (ECM) components and increased matrix-metalloprotease (MMPs) activity are hallmarks of fibrosis. We developed an ELISA for quantification of MMP-9 derived collagen type III (CO3) degradation.......Accumulation of extracellular matrix (ECM) components and increased matrix-metalloprotease (MMPs) activity are hallmarks of fibrosis. We developed an ELISA for quantification of MMP-9 derived collagen type III (CO3) degradation....

Spontaneous and cytokine induced expression and activity of matrix metalloproteinases in human colonic epithelium

DEFF Research Database (Denmark)

Pedersen, G; Saermark, T; Kirkegaard, T

2009-01-01

levels in cells from inflamed IBD mucosa. MMP-2 and -8 mRNA were expressed inconsistently and MMP-11, -13 and -14 mRNA undetectable. Proteolytic MMP activity was detected in CEC supernatants and the level was increased significantly in inflamed IBD epithelium. The enzyme activity was inhibited strongly......Matrix metalloproteinases (MMPs) have been implicated in tissue damage associated with inflammatory bowel disease (IBD).As the role of the intestinal epithelium in this process is unknown, we determined MMP expression and enzyme activity in human colonic epithelial cells (CEC). MMP mRNA expression...... was assessed by reverse transcription-polymerase chain reaction in HT-29 and DLD-1 cells and in CEC isolated from biopsies from IBD and control patients. Total MMP activity in the cells was measured by a functional assay, based on degradation of a fluorescent synthetic peptide containing the specific bond...

Ultrasound-responsive gene-activated matrices for osteogenic gene therapy using matrix-assisted sonoporation.

Science.gov (United States)

Nomikou, N; Feichtinger, G A; Saha, S; Nuernberger, S; Heimel, P; Redl, H; McHale, A P

2018-01-01

Gene-activated matrix (GAM)-based therapeutics for tissue regeneration are limited by efficacy, the lack of spatiotemporal control and availability of target cells, all of which impact negatively on their translation to the clinic. Here, an advanced ultrasound-responsive GAM is described containing target cells that facilitates matrix-assisted sonoporation (MAS) to induce osteogenic differentiation. Ultrasound-responsive GAMs consisting of fibrin/collagen hybrid-matrices containing microbubbles, bone morphogenetic protein BMP2/7 coexpression plasmids together with C2C12 cells were treated with ultrasound either in vitro or following parenteral intramuscular implantation in vivo. Using direct measurement for alkaline phosphatase activity, von Kossa staining and immunohistochemical analysis for osteocalcin expression, MAS-stimulated osteogenic differentiation was confirmed in the GAMs in vitro 7 days after treatment with ultrasound. At day 30 post-treatment with ultrasound, ectopic osteogenic differentiation was confirmed in vivo using X-ray microcomputed tomography and histological analysis. Osteogenic differentiation was indicated by the presence of ectopic bone structures in all animals treated with MAS. In addition, bone volumes in this group were statistically greater than those in the control groups. This novel approach of incorporating a MAS capability into GAMs could be exploited to facilitate ex vivo gene transfer with subsequent surgical implantation or alternatively provide a minimally invasive means of stimulating in situ transgene delivery for osteoinductive gene-based therapies. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Simulation of sparse matrix array designs

Science.gov (United States)

Boehm, Rainer; Heckel, Thomas

2018-04-01

Matrix phased array probes are becoming more prominently used in industrial applications. The main drawbacks, using probes incorporating a very large number of transducer elements, are needed for an appropriate cabling and an ultrasonic device offering many parallel channels. Matrix arrays designed for extended functionality feature at least 64 or more elements. Typical arrangements are square matrices, e.g., 8 by 8 or 11 by 11 or rectangular matrixes, e.g., 8 by 16 or 10 by 12 to fit a 128-channel phased array system. In some phased array systems, the number of simultaneous active elements is limited to a certain number, e.g., 32 or 64. Those setups do not allow running the probe with all elements active, which may cause a significant change in the directivity pattern of the resulting sound beam. When only a subset of elements can be used during a single acquisition, different strategies may be applied to collect enough data for rebuilding the missing information from the echo signal. Omission of certain elements may be one approach, overlay of subsequent shots with different active areas may be another one. This paper presents the influence of a decreased number of active elements on the sound field and their distribution on the array. Solutions using subsets with different element activity patterns on matrix arrays and their advantages and disadvantages concerning the sound field are evaluated using semi-analytical simulation tools. Sound field criteria are discussed, which are significant for non-destructive testing results and for the system setup.