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Kazuei Igarashi - One of the best experts on this subject based on the ideXlab platform.
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Protein-conjugated Acrolein as a biochemical marker of brain infarction.
Molecular Nutrition & Food Research, 2011Co-Authors: Kazuei Igarashi, Keiko KashiwagiAbstract:The relationship between Acrolein (CH(2) =CH-CHO) and brain infarction is the focus of this review. It has been found that Acrolein is produced mainly within cells from polyamines by polyamine oxidases (PAOs), especially from spermine by spermine oxidase during cell damage, and that Acrolein is more toxic than reactive oxygen species (ROS) in a cell culture system. Thus, the possibility that Acrolein and PAOs are good biochemical markers of stroke was tested because there are no other reliable biochemical markers at the early stage of stroke. Levels of protein-conjugated Acrolein (PC-Acro) and PAOs (Acrolein-producing enzymes) were significantly increased in the plasma of stroke patients. The multiplied value of PC-Acro by PAOs was nearly parallel with the size of stroke. Furthermore, when the combined measurements of PC-Acro, interleukin-6 (IL-6) and C-reactive protein (CRP) were evaluated along with age using a receiver operating characteristic (ROC) curve, even silent brain infarction (SBI), which is a small brain infarction, was indicated with approximately 84% sensitivity and specificity. These findings clearly indicate that Acrolein is strongly correlated with cell damage during brain infarction.
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intense correlation between brain infarction and protein conjugated Acrolein
Stroke, 2009Co-Authors: Ryotaro Saiki, Keiko Kashiwagi, Kazuhiro Nishimura, Itsuko Ishii, Tomohiro Omura, Shigeru Okuyama, Kazuei IgarashiAbstract:Background and Purpose— 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. Methods— 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. Results— The level of protein-conjugated Acrolein was greatly increased, and levels of spermine an...
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Acrolein toxicity comparison with reactive oxygen species
Biochemical and Biophysical Research Communications, 2009Co-Authors: Madoka Yoshida, Keiko Kashiwagi, Hideyuki Tomitori, Yoshiki Machi, Motofumi Hagihara, Kyohei Higashi, Hitomi Goda, Takeshi Ohya, Masaru Niitsu, Kazuei IgarashiAbstract:Abstract The toxicity of Acrolein was compared with that of reactive oxygen species using a mouse mammary carcinoma FM3A cell culture system. Complete inhibition of cell growth was accomplished with 10 μM Acrolein, 100 μM H2O2, and 20 μM H2O2 plus 1 mM vitamin C, which produce OH, suggesting that toxicity of Acrolein is more severe than H2O2 and nearly equal to that of OH, when these compounds were added extracellularly. Acrolein toxicity was prevented by N-acetyl- l -cysteine and N-benzylhydroxylamine, and attenuated by putrescine and spermidine. Toxicity of H2O2 was prevented by glutathione peroxidase plus N-acetyl- l -cysteine, pyruvate, catalase, and reduced by polyphenol, and toxicity of OH was prevented by glutathione peroxidase plus N-acetyl- l -cysteine, pyruvate, catalase and reduced by N-acetyl- l -cysteine. The results indicate that prevention of cell toxicity by N-acetyl- l -cysteine was more effective with Acrolein than with OH. Protein and DNA synthesis was damaged primarily by Acrolein and reactive oxygen species, respectively.
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polyamine oxidase and Acrolein as novel biochemical markers for diagnosis of cerebral stroke
Stroke, 2005Co-Authors: Hideyuki Tomitori, Keiko Kashiwagi, Kazuhiro Nishimura, Teruyoshi Usui, Naokatsu Saeki, Shiro Ueda, Hiroshi Kase, Kazuei IgarashiAbstract:Background and Purpose— We found previously that plasma levels of Acrolein (CH2=CHCHO) and spermine oxidase (SMO) were well correlated with the degree of severity of chronic renal failure. The aim of this study was to test whether the levels of these 2 markers and of acetylpolyamine oxidase (AcPAO) were increased in the plasma of stroke patients. Methods— The activity of AcPAO and SMO and the level of protein-conjugated Acrolein in plasma of the stroke patients and normal subjects were measured by high-performance liquid chromatography and ELISA, respectively. Focal infarcts were estimated by MRI or computed tomography (CT). Results— The levels of AcPAO, SMO, and Acrolein were significantly increased in the plasma of stroke patients. The size of stroke was nearly parallel with the multiplied value of Acrolein and total polyamine oxidase (AcPAO plus SMO). After the onset of stroke, an increase in AcPAO first occurred, followed by increased levels of SMO and finally Acrolein. In 1 case, an increase in AcPAO...
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increase in putrescine amine oxidase and Acrolein in plasma of renal failure patients
Biochemical and Biophysical Research Communications, 2003Co-Authors: Kaori Sakata, Keiko Kashiwagi, Shiro Ueda, Shahana Sharmin, Yasubumi Irie, Noriyoshi Murotani, Kazuei IgarashiAbstract:Since polyamines have been suggested to be one of the uremic "toxins," the levels of each polyamine, its oxidized product, Acrolein, and amine oxidase in plasma of patients with renal failure were investigated. The level of putrescine was increased, whereas the level of spermine was decreased in the plasma of patients with renal failure. The patients also had increased serum amine oxidase activity leading to increased degradation of spermine. Both levels of free and protein-conjugated Acrolein were also increased in plasma of patients with renal failure. The accumulated Acrolein found as protein conjugates was equivalent to 180 microM, which was 6-fold higher than in plasma of normal subjects. It was found that Acrolein is mainly produced by polyamine oxidase in plasma. A cell lysate containing polyamine oxidase was cytotoxic in the presence of spermine. Our results indicate that the level of Acrolein is well correlated with the degree of seriousness of chronic renal failure.
Koji Uchida - One of the best experts on this subject based on the ideXlab platform.
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quantitative analysis of Acrolein specific adducts generated during lipid peroxidation modification of proteins in vitro identification of nτ 3 propanal histidine as the major adduct
Chemical Research in Toxicology, 2012Co-Authors: Takuya Maeshima, Yoshichika Kawai, Kazuya Honda, Takahiro Shibata, Miho Chikazawa, Mitsugu Akagawa, Koji UchidaAbstract:Acrolein, a ubiquitous pollutant in the environment, is endogenously formed through oxidation reactions and is believed to be involved in cytopathological effects observed during oxidative stress. Acrolein exerts these effects because of its facile reactivity with biological materials, particularly proteins. In the present study, we quantitatively analyzed the Acrolein-specific adducts generated during lipid peroxidation–modification of proteins and identified the Acrolein adduct most abundantly generated in the in vitro oxidized low-density lipoproteins (LDL). Taking advantage of the fact that the Acrolein–lysine adducts, Ne-(3-formyl-3,4-dehydropiperidino)lysine (FDP-lysine) and Ne-(3-methylpyridinium)lysine (MP-lysine), have stable core structures resistant to the acid hydrolysis condition of proteins, we examined the formation of these adducts in proteins using high performance liquid chromatography with online electrospray ionization tandem mass spectrometry. However, only MP-lysine was detected as a...
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monoclonal antibody against protein bound glutathione use of glutathione conjugate of Acrolein modified proteins as an immunogen
Chemical Research in Toxicology, 2012Co-Authors: Atsunori Furuhata, Yoshichika Kawai, Kazuya Honda, Takahiro Shibata, Miho Chikazawa, Noriyuki Shibata, Koji UchidaAbstract:Acrolein shows a facile reactivity with the e-amino group of lysine to form Ne-(3-formyl-3,4-dehydropiperidino)lysine (FDP-lysine) as the major product. In addition, FDP-lysine generated in the Acrolein-modified protein could function as an electrophile, reacting with thiol compounds, to form an irreversible thioether adduct. In the present study, to establish the utility of this irreversible conjugate, we attempted to use it as an immunogen to raise a monoclonal antibody (mAb), which specifically recognized protein-bound thiol compounds. Using the glutathione (GSH) conjugate of the Acrolein-modified protein as an immunogen, we raised the mAb 2C4, which cross-reacted with the GSH conjugate of Acrolein-modified proteins. Specificity studies revealed that mAb 2C4 recognized both the GSH conjugate of an Acrolein–lysine adduct, FDP-lysine, and oxidized GSH (GSSG). In addition, mAb 2C4 cross-reacted not only with the GSH conjugates of the Acrolein-modified protein but also with the GSH-treated, oxidized protei...
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Acrolein impairs atp binding cassette transporter a1 dependent cholesterol export from cells through site specific modification of apolipoprotein a i
Journal of Biological Chemistry, 2005Co-Authors: Baohai Shao, Koji Uchida, Thomas O Mcdonald, Pattie S Green, Kevin D Obrien, John F Oram, Jay W HeineckeAbstract:Acrolein is a highly reactive alpha,beta-unsaturated aldehyde, but the factors that control its reactions with nucleophilic groups on proteins remain poorly understood. Lipid peroxidation and threonine oxidation by myeloperoxidase are potential sources of Acrolein during inflammation. Because both pathways are implicated in atherogenesis and high density lipoprotein (HDL) is anti-atherogenic, we investigated the possibility that Acrolein might target the major protein of HDL, apolipoprotein A-I (apoA-I), for modification. Tandem mass spectrometric analysis demonstrated that lysine 226, located near the center of helix 10 in apoA-I, was the major site modified by Acrolein. Importantly, this region plays a critical role in the cellular interactions and ability of apoA-I to transport lipid. Indeed, we found that conversion of Lys-226 to N(epsilon)-(3-methylpyridinium)lysine by Acrolein associated quantitatively with decreased cholesterol efflux from cells via the ATP-binding cassette transporter A1 pathway. In the crystal structure of truncated apoA-I, Glu-234 lies adjacent to Lys-226, suggesting that negatively charged residues might direct the modification of specific lysine residues in proteins. Finally, immunohistochemical studies with a monoclonal antibody revealed co-localization of apoA-I with Acrolein adducts in human atherosclerotic lesions. Our observations suggest that Acrolein might interfere with normal reverse cholesterol transport by HDL by modifying specific sites in apoA-I. Thus, Acrolein might contribute to atherogenesis by impairing cholesterol removal from the artery wall.
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formation of Acrolein derived 2 deoxyadenosine adduct in an iron induced carcinogenesis model
Journal of Biological Chemistry, 2003Co-Authors: Yoshichika Kawai, Shinya Toyokuni, Atsunori Furuhata, Yasuaki Aratani, Koji UchidaAbstract:Abstract Acrolein is a representative carcinogenic aldehyde found ubiquitously in the environment and formed endogenously through oxidation reactions, such as lipid peroxidation and myeloperoxidase-catalyzed amino acid oxidation. It shows facile reactivity toward DNA to form an exocyclic DNA adduct. To verify the formation of Acrolein-derived DNA adduct under oxidative stress in vivo, we raised a novel monoclonal antibody (mAb21) against the Acrolein-modified DNA and found that the antibody most significantly recognized an Acrolein-modified 2′ -deoxyadenosine. On the basis of chemical and spectroscopic evidence, the major antigenic product of mAb21 was the 1,N6-propano-2′ -deoxyadenosine adduct. The exposure of rat liver epithelial RL34 cells to Acrolein resulted in a significant accumulation of the Acrolein-2′ -deoxyadenosine adduct in the nuclei. Formation of this adduct under oxidative stress in vivo was immunohistochemically examined in rats exposed to ferric nitrilotriacetate, a carcinogenic iron chelate that specifically induces oxidative stress in the kidneys of rodents. It was observed that the Acrolein-2′ -deoxyadenosine adduct was formed in the nuclei of the proximal tubular cells, the target cells of this carcinogenesis model. The same cells were stained with a monoclonal antibody 5F6 that recognizes an Acrolein-lysine adduct, by which cytosolic accumulation of Acrolein-modified proteins appeared. Similar results were also obtained from myeloperoxidase knockout mice exposed to the iron complex, suggesting that the myeloperoxidase-catalyzed oxidation system might not be essential for the generation of Acrolein in this experimental animal carcinogenesis model. The data obtained in this study suggest that the formation of a carcinogenic aldehyde through lipid peroxidation may be causally involved in the pathophysiological effects associated with oxidative stress.
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immunohistochemical detection of lipid peroxidation products protein bound Acrolein and 4 hydroxynonenal protein adducts in actinic elastosis of photodamaged skin
Archives of Dermatological Research, 2001Co-Authors: Nobuhiko Tanaka, Koji Uchida, Shingo Tajima, Akira Ishibashi, Takeshi ShigematsuAbstract:Acrolein and 4-hydroxy-2-nonenal (HNE) are both byproducts of a lipid peroxidation reaction. Actinic elastosis in photodamaged skin of aged individuals is characterized by the accumulation of fragmented elastic fibers in the sun-exposed areas. To study whether a lipid peroxidation reaction is involved in the accumulation of altered elastic fibers in actinic elastosis, skin specimens obtained from sun-damaged areas were immunohistochemically examined using the antibodies against Acrolein and HNE. Both antibodies were found to react with the accumulations of elastic material. Double immunofluorescence labeling demonstrated that Acrolein/elastin and HNE/elastin were colocalized in the actinic elastosis. Western blot analysis showed that the polypeptide with a molecular weight of 62 kDa reacted with anti-Acrolein, anti-HNE and anti-elastin antibodies. The results suggest that Acrolein and HNE may be associated with actinic elastosis.
Thomas Henle - One of the best experts on this subject based on the ideXlab platform.
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identification and quantitation of the lipation product 2 amino 6 3 methylpyridin 1 ium 1 yl hexanoic acid mp lysine in peanuts
Journal of Agricultural and Food Chemistry, 2016Co-Authors: Martin Globisch, Meike Deuber, Thomas HenleAbstract:The lipid peroxidation product Acrolein was semiquantitated by GC-MS (EI) in unheated and heated peanut oil, respectively, representing a model system for peanut roasting. Depending on the heating time, Acrolein levels significantly increased from 0.2 to 10.7 mg/kg oil. As a result of heating Nα-acetyl-l-lysine and Acrolein, the pyridinium derivative 2-acetamido-6-(3-methylpyridin-1-ium-1-yl)hexanoic acid (MP-acetyl lysine) was identified. In addition, the lysine derivative 2-amino-6-[5-(hydroxymethyl)-3,6-dihydro-2H-pyridin-1-yl]hexanoic acid was identified after reduction and hydrolysis. After preparation of 2-amino-6-(3-methylpyridin-1-ium-1-yl)hexanoic acid (MP-lysine) as reference material, its amounts were quantitated in Acrolein-modified peanut proteins by HPLC-ESI-MS/MS after acid hydrolysis, showing that at low Acrolein concentrations, the modification of lysine could be entirely explained by the formation of MP-lysine. Furthermore, for the first time, MP-lysine was quantitated in peanut samples ...
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Identification and Quantitation of the Lipation Product 2‑Amino-6-(3-methylpyridin-1-ium-1-yl)hexanoic Acid (MP-Lysine) in Peanuts
2016Co-Authors: Martin Globisch, Meike Deuber, Thomas HenleAbstract:The lipid peroxidation product Acrolein was semiquantitated by GC-MS (EI) in unheated and heated peanut oil, respectively, representing a model system for peanut roasting. Depending on the heating time, Acrolein levels significantly increased from 0.2 to 10.7 mg/kg oil. As a result of heating Nα-acetyl-l-lysine and Acrolein, the pyridinium derivative 2-acetamido-6-(3-methylpyridin-1-ium-1-yl)hexanoic acid (MP-acetyl lysine) was identified. In addition, the lysine derivative 2-amino-6-[5-(hydroxymethyl)-3,6-dihydro-2H-pyridin-1-yl]hexanoic acid was identified after reduction and hydrolysis. After preparation of 2-amino-6-(3-methylpyridin-1-ium-1-yl)hexanoic acid (MP-lysine) as reference material, its amounts were quantitated in Acrolein-modified peanut proteins by HPLC-ESI-MS/MS after acid hydrolysis, showing that at low Acrolein concentrations, the modification of lysine could be entirely explained by the formation of MP-lysine. Furthermore, for the first time, MP-lysine was quantitated in peanut samples in amounts up to 10.2 mg/kg, showing an increase depending on the roasting time. Thus, MP-lysine might represent a marker to evaluate the extent of food protein lipation by Acrolein
Keiko Kashiwagi - One of the best experts on this subject based on the ideXlab platform.
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Protein-conjugated Acrolein as a biochemical marker of brain infarction.
Molecular Nutrition & Food Research, 2011Co-Authors: Kazuei Igarashi, Keiko KashiwagiAbstract:The relationship between Acrolein (CH(2) =CH-CHO) and brain infarction is the focus of this review. It has been found that Acrolein is produced mainly within cells from polyamines by polyamine oxidases (PAOs), especially from spermine by spermine oxidase during cell damage, and that Acrolein is more toxic than reactive oxygen species (ROS) in a cell culture system. Thus, the possibility that Acrolein and PAOs are good biochemical markers of stroke was tested because there are no other reliable biochemical markers at the early stage of stroke. Levels of protein-conjugated Acrolein (PC-Acro) and PAOs (Acrolein-producing enzymes) were significantly increased in the plasma of stroke patients. The multiplied value of PC-Acro by PAOs was nearly parallel with the size of stroke. Furthermore, when the combined measurements of PC-Acro, interleukin-6 (IL-6) and C-reactive protein (CRP) were evaluated along with age using a receiver operating characteristic (ROC) curve, even silent brain infarction (SBI), which is a small brain infarction, was indicated with approximately 84% sensitivity and specificity. These findings clearly indicate that Acrolein is strongly correlated with cell damage during brain infarction.
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intense correlation between brain infarction and protein conjugated Acrolein
Stroke, 2009Co-Authors: Ryotaro Saiki, Keiko Kashiwagi, Kazuhiro Nishimura, Itsuko Ishii, Tomohiro Omura, Shigeru Okuyama, Kazuei IgarashiAbstract:Background and Purpose— 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. Methods— 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. Results— The level of protein-conjugated Acrolein was greatly increased, and levels of spermine an...
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Acrolein toxicity comparison with reactive oxygen species
Biochemical and Biophysical Research Communications, 2009Co-Authors: Madoka Yoshida, Keiko Kashiwagi, Hideyuki Tomitori, Yoshiki Machi, Motofumi Hagihara, Kyohei Higashi, Hitomi Goda, Takeshi Ohya, Masaru Niitsu, Kazuei IgarashiAbstract:Abstract The toxicity of Acrolein was compared with that of reactive oxygen species using a mouse mammary carcinoma FM3A cell culture system. Complete inhibition of cell growth was accomplished with 10 μM Acrolein, 100 μM H2O2, and 20 μM H2O2 plus 1 mM vitamin C, which produce OH, suggesting that toxicity of Acrolein is more severe than H2O2 and nearly equal to that of OH, when these compounds were added extracellularly. Acrolein toxicity was prevented by N-acetyl- l -cysteine and N-benzylhydroxylamine, and attenuated by putrescine and spermidine. Toxicity of H2O2 was prevented by glutathione peroxidase plus N-acetyl- l -cysteine, pyruvate, catalase, and reduced by polyphenol, and toxicity of OH was prevented by glutathione peroxidase plus N-acetyl- l -cysteine, pyruvate, catalase and reduced by N-acetyl- l -cysteine. The results indicate that prevention of cell toxicity by N-acetyl- l -cysteine was more effective with Acrolein than with OH. Protein and DNA synthesis was damaged primarily by Acrolein and reactive oxygen species, respectively.
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polyamine oxidase and Acrolein as novel biochemical markers for diagnosis of cerebral stroke
Stroke, 2005Co-Authors: Hideyuki Tomitori, Keiko Kashiwagi, Kazuhiro Nishimura, Teruyoshi Usui, Naokatsu Saeki, Shiro Ueda, Hiroshi Kase, Kazuei IgarashiAbstract:Background and Purpose— We found previously that plasma levels of Acrolein (CH2=CHCHO) and spermine oxidase (SMO) were well correlated with the degree of severity of chronic renal failure. The aim of this study was to test whether the levels of these 2 markers and of acetylpolyamine oxidase (AcPAO) were increased in the plasma of stroke patients. Methods— The activity of AcPAO and SMO and the level of protein-conjugated Acrolein in plasma of the stroke patients and normal subjects were measured by high-performance liquid chromatography and ELISA, respectively. Focal infarcts were estimated by MRI or computed tomography (CT). Results— The levels of AcPAO, SMO, and Acrolein were significantly increased in the plasma of stroke patients. The size of stroke was nearly parallel with the multiplied value of Acrolein and total polyamine oxidase (AcPAO plus SMO). After the onset of stroke, an increase in AcPAO first occurred, followed by increased levels of SMO and finally Acrolein. In 1 case, an increase in AcPAO...
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increase in putrescine amine oxidase and Acrolein in plasma of renal failure patients
Biochemical and Biophysical Research Communications, 2003Co-Authors: Kaori Sakata, Keiko Kashiwagi, Shiro Ueda, Shahana Sharmin, Yasubumi Irie, Noriyoshi Murotani, Kazuei IgarashiAbstract:Since polyamines have been suggested to be one of the uremic "toxins," the levels of each polyamine, its oxidized product, Acrolein, and amine oxidase in plasma of patients with renal failure were investigated. The level of putrescine was increased, whereas the level of spermine was decreased in the plasma of patients with renal failure. The patients also had increased serum amine oxidase activity leading to increased degradation of spermine. Both levels of free and protein-conjugated Acrolein were also increased in plasma of patients with renal failure. The accumulated Acrolein found as protein conjugates was equivalent to 180 microM, which was 6-fold higher than in plasma of normal subjects. It was found that Acrolein is mainly produced by polyamine oxidase in plasma. A cell lysate containing polyamine oxidase was cytotoxic in the presence of spermine. Our results indicate that the level of Acrolein is well correlated with the degree of seriousness of chronic renal failure.
Riyi Shi - One of the best experts on this subject based on the ideXlab platform.
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dimercaprol is an Acrolein scavenger that mitigates Acrolein mediated pc 12 cells toxicity and reduces Acrolein in rat following spinal cord injury
Journal of Neurochemistry, 2017Co-Authors: Ran Tian, Riyi ShiAbstract: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.
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Acrolein-mediated injury in nervous system trauma and diseases.
Molecular nutrition & food research, 2011Co-Authors: Riyi Shi, Todd Rickett, Wenjing SunAbstract: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.
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chitosan nanoparticle based neuronal membrane sealing and neuroprotection following Acrolein induced cell injury
Journal of Biological Engineering, 2010Co-Authors: Youngnam Cho, Riyi Shi, Richard B BorgensAbstract: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.
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Acrolein induced cell death in pc12 cells role of mitochondria mediated oxidative stress
Neurochemistry International, 2005Co-Authors: Jian Luo, Paul J Robinson, Riyi ShiAbstract: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.
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Acrolein inflicts axonal membrane disruption and conduction loss in isolated guinea pig spinal cord
Neuroscience, 2002Co-Authors: Riyi Shi, Jian Luo, Melissa A PeasleyAbstract:We have examined the effect of Acrolein, an aldehyde product of lipid peroxidation, on axons in isolated guinea-pig spinal cord white matter. We found that 200 μM Acrolein, but not 50 μM, induced a time-dependent loss of compound action potential conduction. Such conduction loss was irreversible within 1 h after Acrolein perfusion. Parallel anatomical assessment indicates membrane integrity breakdown based on a horseradish peroxidase-exclusion assay. This is the first report to suggest that Acrolein inflicts severe axonal damage. Since axonal damage within white matter plays a key role in the pathology of traumatic spinal cord injury, we suggest that Acrolein may be a critical factor in mediating secondary functional loss.
