Induction of Apoptotic Cell Death by Methylglyoxal and 3-Deoxyglucosone in Macrophage-Derived Cell Lines

Okado, Ayako; Kawasaki, Yoichi; Hasuike, Yukiko; Takahashi, M.; Teshima, Tadashi; Fujii, Junichi; Taniguchi, Naoyuki

doi:10.1006/bbrc.1996.1157

Cited by 170 publications

(97 citation statements)

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“…9) This result consists with our present observation in BAECs. However, the levels of intracellular GSH were little changed in U937 cells incubated with MG, 9) though MG affected GSH levels in BAECs. 17) This discrepancy may be related to the differences in cells.…”

Section: Discussionsupporting

confidence: 91%

“…In the case of rat Schwann cells or human monocytic leukemia U937 cells, MG-induced apoptosis was inhibited by NAC (2 or 20 mM). 8,9) The sulfhydryl group of NAC provides a substrate for GSH synthesis. However, NAC reacts directly with MG. 32) Exogenous GSH does not permeate the cell membrane easily.…”

Section: Discussionmentioning

confidence: 99%

“…[7][8][9][10] We examined the effect of BSO on MG-induced apoptosis of BAECs. An early feature of cells undergoing apoptosis is the externalization of phosphatidylserine from the inner leaflet of the plasma membrane to the outer surface of the cells.…”

Section: Effect Of Bso On Viability Of Baecs Exposed To Mgmentioning

confidence: 99%

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Buthionine Sulfoximine Promotes Methylglyoxal-Induced Apoptotic Cell Death and Oxidative Stress in Endothelial Cells

Takahashi

Tatsunami

Oba

et al. 2010

Biological & Pharmaceutical Bulletin

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Methylglyoxal (MG) is a reactive dicarbonyl compound that is formed as a metabolic byproduct of glycolysis. 1,2) MG is found at high levels in the blood of diabetic patients. 3) MG causes nonenzymatic glycation of proteins to yield irreversible advanced glycation end products (AGEs), leading to cross-linking or degradation of proteins. 4) MG has been linked to the development of diabetic complications related to vascular injury. [3][4][5] MG might contribute to not only the development of diabetes but also the pathogenesis of hypertension. 6) MG induces the apoptosis of Schwann cells, 7,8) human monocytic leukemia U937 cells, 9) and human umbilical vein endothelial cells. 10) It is suggested that oxidative stress is involved in MG-induced apoptosis. Oxidative stress resulting from the accumulation of reactive oxygen species (ROS) has been well characterized in diabetic complications. 11,12) MG inactivates antioxidant enzymes, such as glutathione peroxidase and Cu,Zn-superoxide dismutase. 13,14) The dysfunction of antioxidant defense systems may lead to the progression of oxidative stress and finally cell death, such as apoptosis.Reduced glutathione (GSH), the most abundant non-protein thiol antioxidant in cells, is important for protection against oxidative injury. Chronic intake of MG by mice caused the depletion of blood GSH. 15) Intracellular GSH was depleted in Schwann cells incubated with MG. 8) It was also revealed that N-acetyl-L-cysteine, an antioxidant, restored the MG-induced GSH depletion in Schwann cells and prevented apoptosis. In human monocytic leukemia U937 cells, MG-induced apoptosis and oxidative stress were enhanced by DLbuthionine-(S,R)-sulfoximine (BSO), an inhibitor of GSH biosynthesis, and partially blocked by N-acetyl-L-cysteine. 9) However, it remains unknown whether BSO or N-acetyl-Lcysteine affects MG-induced apoptosis and oxidative stress in endothelial cells. Recently, we reported that MG induces apoptosis and oxidative stress in bovine aortic endothelial cells (BAECs). 16,17) MG affected GSH levels in BAECs. 17) In this study, we examined the effect of BSO on MG-induced apoptosis and oxidative stress by using BAECs. MATERIALS AND METHODSMaterials MG (40% aqueous solution), BSO, and p-nitrophenyl phosphate were purchased from Sigma Chemical Co. (St. Louis, MO, U.S.A.). Fetal bovine serum (FBS) was from Lonza (Walkersville, MD, U.S.A.). Dulbecco's modified Eagle's medium (DMEM), Dulbecco's phosphate-buffered saline (DPBS), phosphate-buffered saline (PBS) at pH 7.4, Lglutamine, penicillin, and streptomycin were from Gibco BRL (Grand Island, NY, U.S.A.). All other chemicals used were of reagent grade.Endothelial Cell Culture BAECs were purchased from Lonza. Cells were obtained at the third passage, transferred to 75 cm 2 filter vent flasks, and grown to 80-90% confluence in DMEM containing 10% FBS, 4 nM L-glutamine, 100 U/ml penicillin, and 100 mg/ml streptomycin, with incubation at 37°C in a humidified atmosphere of 5% CO 2 and 95% air. Cells were passaged by trypsinization and those b...

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

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Buthionine Sulfoximine Promotes Methylglyoxal-Induced Apoptotic Cell Death and Oxidative Stress in Endothelial Cells

Takahashi

Tatsunami

Oba

et al. 2010

Biological & Pharmaceutical Bulletin

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“…MG rapidly generates ROS including superoxides, during the glycation reaction (36), increases ROS in hepatocytes (35). MG and 3-DG also induce apoptotic cell death in macrophage-derived cell lines (44). Chronic exposure to abnormally high concentrations of these dicarbonyl, therefore, may be a contributing factor in oxidative stress in diabetes mellitus.…”

Section: Discussionmentioning

confidence: 99%

Selective Induction of Heparin-binding Epidermal Growth Factor-like Growth Factor by Methylglyoxal and 3-Deoxyglucosone in Rat Aortic Smooth Muscle Cells

Che

Asahi

Takahashi

et al. 1997

Journal of Biological Chemistry

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103

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Methylglyoxal (MG) and 3-deoxyglucosone (3-DG), reactive dicarbonyl metabolites in the glyoxalase system and glycation reaction, respectively, selectively induced heparin-binding epidermal growth factor (HB-EGF)-like growth factor mRNA in a dose-and time-dependent manner in rat aortic smooth muscle cells (RASMC). A nuclear run-on assay revealed that the dicarbonyl may regulate expression of HB-EGF at the transcription level. The dicarbonyl also increased the secretion of HB-EGF from RASMC. However, platelet-derived growth factor, another known growth factor of smooth muscle cells (SMC), was not induced by both dicarbonyls. The dicarbonyl augmented intracellular peroxides prior to the induction of HB-EGF mRNA as judged by flow cytometric analysis using 2 ,7 -dichlorofluorescin diacetate. N-Acetyl-L-cysteine and aminoguanidine suppressed both dicarbonyl-increased HB-EGF mRNA and intracellular peroxide levels in RASMC. DL-Buthionine-(S,R)-sulfoximine increased the levels of 3-DG-induced HB-EGF mRNA. Furthermore, hydrogen peroxide alone also induced HB-EGF mRNA in RASMC. These results indicate that MG and 3-DG induce HB-EGF by increasing the intracellular peroxide levels. In addition, the pretreatment with 12-O-tetra-decanoylphorbol-13-acetate failed to alter dicarbonyl-induced HB-EGF mRNA expression in RASMC, suggesting that the signal transducing mechanism is not mediated by protein kinase C. Since HB-EGF is known as a potent mitogen for smooth muscle cells and is abundant in atherosclerotic plaques, the induction of HB-EGF by MG and 3-DG, as well as the concomitant increment of intracellular peroxides, may trigger atherogenesis during diabetes.Methylglyoxal (2-oxopropanal; MG), 1 a reactive ␣,␤-dicarbonyl metabolite and physiological substrate for the glyoxalase system (1), is formed by the non-enzymatic and enzymatic elimination of phosphate from dihydroxyacetone phosphate, glyceraldehyde-3-phosphate (2, 3), and by the oxidation of hydroxyacetone and aminoacetone (4 -6). The estimated rate of formation of methylglyoxal in tissues of normal healthy subjects is approximately 125 M/day which can largely be accounted for as a result of fragmentation of triose phosphates (2). The glyoxalase system, using reduced glutathione as a cofactor, catalyzes the conversion of methylglyoxal to D-lactate via the intermediate S-D-lactoylglutathione. The formation of methylglyoxal in cultured human red blood cells is increased under hyperglycemic conditions and by the addition of fructose,

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“…Moreover, previous reports have shown that carbonated drinks contain methylglyoxal (MG), which is a highly reactive carbonyl compound and major precursor of advanced glycation end products (AGEs), and displays toxicity in cells and tissues (Tan et al, 2008;Fukunaga et al, 2004;Okado et al, 1996;Ramasamy et al, 2006). Food and beverages represent exogenous sources of MG (Nemet et al, 2006); however, few reports have evaluated the actual effects of drinking and eating such products on plasma MG levels.…”

Section: Introductionmentioning

confidence: 99%

Carbonated soft drinks and carbonyl stress burden

Nakayama

Terawaki

et al. 2009

J. Toxicol. Sci.

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-Carbonated soft drinks reportedly contain methylglyoxal (MG), which is strongly associated with human carbonyl stress. We sought to evaluate the effects of carbonated drink intake on human carbonyl stress. We measured MG levels in 4 commercial beverage brands, and evaluated the changes in plasma MG in healthy subjects following the intake of carbonated drinks. By 30 min after intake of samples containing high glucose and high MG, the levels of plasma MG, glucose, insulin and uric acid had -bonated samples containing little MG, there were no increases in plasma MG. Our results suggest that glucose-containing carbonated soft drinks are associated with increases in not only glucose but also carbonyl burden.

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Induction of Apoptotic Cell Death by Methylglyoxal and 3-Deoxyglucosone in Macrophage-Derived Cell Lines

Cited by 170 publications

References 0 publications

Buthionine Sulfoximine Promotes Methylglyoxal-Induced Apoptotic Cell Death and Oxidative Stress in Endothelial Cells

Buthionine Sulfoximine Promotes Methylglyoxal-Induced Apoptotic Cell Death and Oxidative Stress in Endothelial Cells

Selective Induction of Heparin-binding Epidermal Growth Factor-like Growth Factor by Methylglyoxal and 3-Deoxyglucosone in Rat Aortic Smooth Muscle Cells

Carbonated soft drinks and carbonyl stress burden

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