Erythrocyte membrane interactions with menadione and the mechanism of menadione-induced hemolysis

Mezick, James A.; Settlemire, C. T.; Brierley, Gerald P.; Barefield, Kaye P.; Jensen, Wallace N.; Cornwell, David G.

doi:10.1016/0005-2736(70)90213-0

Cited by 51 publications

(30 citation statements)

References 23 publications

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“…6, which is published as supporting information on the PNAS web site). Because quinone-thiol Michael adducts also function as redox cycling agents (4,9), these data strongly suggest that NAC or DTT abolished ␥-TQ toxicity by eliminating its ability to form Michael adduct with intracellular nucleophiles.…”

Section: Alleviation Of Arylating Quinone Toxicity By Prior Michael Amentioning

confidence: 92%

“…Although all quinones are redox cycling agents that generate reactive oxygen species (ROS), partially substituted quinones also function as arylating agents (1-3, 5, 6). The arylating quinones react with cellular nucleophiles such as thiols on cysteine residues of proteins, glutathione (GSH), and detoxifying agents such as N-acetylcysteine (NAC), forming covalently linked quinonethiol Michael adducts (1-3, 5, 6) that retain the ability to function as redox cycling agents (4,9). In contrast to well studied ROS generation and consequent oxidative stress in living cells (1)(2)(3), the role of Michael adduct formation in quinone toxicity is not well understood.…”

mentioning

confidence: 99%

“…Arylating quinones do have unique biologic properties, such as high cytotoxicity, that are not always shared by nonarylating quinones and arylating quinone-thiol adducts (4)(5)(6)(9)(10)(11)(12). Cellular mechanisms responsible for this cytotoxicity are not well established.…”

mentioning

confidence: 99%

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Mechanism of arylating quinone toxicity involving Michael adduct formation and induction of endoplasmic reticulum stress

Wang¹,

Thomas

Sachdeva

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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154

128

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Quinones permeate our biotic environment, contributing to both homeostasis and cytotoxicity. All quinones generate reactive oxygen species through redox cycling, while partially substituted quinones also undergo arylation (Michael adduct formation) yielding covalent bonds with nucleophiles such as cysteinyl thiols. In contrast to reactive oxygen species, the role of arylation in quinone cytotoxicity is not well understood. We found that the arylating quinones, including unsubstituted 1,4-benzoquinone (1,4-BzQ) and partially substituted vitamin E congener ␥-tocopherol quinone (␥-TQ), were cytotoxic, with ␥-TQ > 1,4-BzQ, whereas the fully substituted nonarylating vitamin E congener ␣-tocopherol quinone was not. In vitro, both arylating quinones formed Michael adducts with the thiol nucleophile N-acetylcysteine (NAC) at rates where 1,4-BzQ > ␥-TQ. In cultured cells, concurrent addition of NAC eliminated 1,4-BzQ caused toxicity, but preincubation was required for the same NAC detoxification effect on ␥-TQ. These data clearly established the role of arylation in quinone toxicity and revealed that arylating quinone structure affects cytotoxicity by governing detoxification through the rate of adduct formation. Furthermore, arylating quinones induced endoplasmic reticulum (ER) stress by activating the pancreatic ER kinase (PERK) signaling pathway including elF2␣, ATF4, and C͞EBP homologous protein (CHOP). Detoxification by NAC greatly attenuates CHOP induction in arylating quinone-treated cells, suggesting that ER stress is a cellular mechanism for arylating quinone cytotoxicity.quinone adduction ͉ thiol nucleophiles ͉ tocopherols ͉ CHOP ͉ cytotoxicity Q uinones and their phenolic precursors are present throughout the biotic environment and include polyphenols and tocopherols in the diet, drugs in medicine, environmental pollutants such as polycyclic aromatic hydrocarbons, and their metabolic products (1-8). They are involved in a wide variety of biological and chemical processes, including electron transport in animals and plants, photosynthesis, posttranslational modification of proteins, metabolism of cellular signaling molecules such as estrogens and catecholamines, metabolism of antioxidant and signaling tocopherol congeners (vitamin E), and the elimination of polycyclic aromatic hydrocarbons introduced by combustion processes associated with our petroleum-based chemical environment.Quinones are a class of highly reactive compounds. Although all quinones are redox cycling agents that generate reactive oxygen species (ROS), partially substituted quinones also function as arylating agents (1-3, 5, 6). The arylating quinones react with cellular nucleophiles such as thiols on cysteine residues of proteins, glutathione (GSH), and detoxifying agents such as N-acetylcysteine (NAC), forming covalently linked quinonethiol Michael adducts (1-3, 5, 6) that retain the ability to function as redox cycling agents (4, 9). In contrast to well studied ROS generation and consequent oxidative stress in living cells (1-3), the role o...

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Section: Alleviation Of Arylating Quinone Toxicity By Prior Michael Amentioning

confidence: 92%

mentioning

confidence: 99%

See 1 more Smart Citation

Mechanism of arylating quinone toxicity involving Michael adduct formation and induction of endoplasmic reticulum stress

Wang¹,

Thomas

Sachdeva

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

154

128

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“…A similar reaction is known to occur with GSH and other thiols (1,(82)(83)(84). When menadione reacts with methemoglobin, formation of the thioether is accompanied by heme reduction to oxyhemoglobin (75).…”

Section: Reaction Of Hemoglobin With Oxidizing Compoundsmentioning

confidence: 73%

Free-radical production and oxidative reactions of hemoglobin.

Winterbourn¹

1985

Environ Health Perspect

153

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Mechanisms of autoxidation of hemoglobin, and its reactions with H2O2, O2-, and oxidizing or reducing xenobiotics are discussed. Reactive intermediates of such reactions can include drug free radicals, H2O2, and O2-, as well as peroxidatively active ferrylhemoglobin and methemoglobin-H2O2. The contributions of these species to hemoglobin denaturation and drug-induced hemolysis, and the actions of various protective agents, are considered.

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“…A modification of the 2-thiobarbituric acid test (13) was used to measure the lipid peroxides. A 0.5 mL aliquot of the erythrocyte membrane suspension was mixed with 1.0 mL of 10% trichloroacetic acid and 2.0 mL of 0.67% of 2-thiobarbituric acid.…”

Section: Modified 2-thiobarbituric Acid Testmentioning

confidence: 99%

Antioxidative Effect of Sesame Lignans in Diabetes Mellitus Blood: an in vitro study

Dhar¹,

Chattopadhyay

Bhattacharyya

et al. 2005

J. Oleo Sci.

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Refined and bleached sesame oil (Sesamum indicum L.) contains sesame lignans, mainly sesamin and episesamin, and they are isolated from refined sesame oil. The in vitro antioxidant properties of sesame lignans and sesamol are investigated on oxidative modification of human plasma, low-density lipoprotein (LDL) and erythrocyte membrane lipid. Blood samples are collected from diabetic and non-diabetic (normal) healthy individuals. Sesame lignans and sesamol are added at 0.05% and 0.1% concentrations to plasma, LDL and erythrocyte membrane isolated from the respective blood samples and peroxidations are determined against control samples. A significant increase of peroxidation levels was observed consequently in diabetic control blood and the non-diabetic control blood. Sesamol and sesame lignans decreased lipid peroxidation. The findings suggest that sesamol and sesame lignans (mainly sesamin and episesamin) are potentially effective antioxidants that can protect plasma, LDL and erythrocyte membrane from oxidation which may be effective in reducing the risk of coronary heart disease in diabetes.

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Erythrocyte membrane interactions with menadione and the mechanism of menadione-induced hemolysis

Cited by 51 publications

References 23 publications

Mechanism of arylating quinone toxicity involving Michael adduct formation and induction of endoplasmic reticulum stress

Mechanism of arylating quinone toxicity involving Michael adduct formation and induction of endoplasmic reticulum stress

Free-radical production and oxidative reactions of hemoglobin.

Antioxidative Effect of Sesame Lignans in Diabetes Mellitus Blood: an in vitro study

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