Analysis of DNA–protein crosslinking activity of malondialdehyde in vitro

Voitkun, Victoria; Zhitkovich, Anatoly

doi:10.1016/s0027-5107(99)00011-1

Cited by 101 publications

(73 citation statements)

References 38 publications

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“…An age-related accumulation of DPCs has also been observed in mouse organs (2), supporting the hypothesis that oxidative mechanisms contribute to the formation of these DNA damages (2,3). DPC levels increase dramatically upon exposure to a variety of physical or chemical agents, including UV light (4), ionizing radiation (5), ␤-propiolactone (6), aldehydes (1,(7)(8)(9), arsenite (10), ferric nitrilotriacetate (11), chromate (12), nickel (13), and others. Chemotherapeutic agents, such as cisplatin (12,14), bisplatinum (15), and neocarcinostatin (16), have also been shown to induce DPC formation.…”

mentioning

confidence: 61%

“…Many endogenous compounds (e.g., metabolites of lipid peroxidation) as well as environmental agents are reactive with both DNA and proteins and thus can produce covalent linkage between these two types of macromolecules (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). DNA-protein crosslinks (DPCs) represent a relatively abundant form of DNA damage as evidenced by data indicating that the background level of DPCs in human white blood cells ranged from 0.5 to 4.5 per 10 7 bases (1).…”

mentioning

confidence: 99%

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Incision of DNA–protein crosslinks by UvrABC nuclease suggests a potential repair pathway involving nucleotide excision repair

Minko

Zou

Lloyd

2002

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

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DNA-protein crosslinks (DPCs) arise in biological systems as a result of exposure to a variety of chemical and physical agents, many of which are known or suspected carcinogens. The biochemical pathways for the recognition and repair of these lesions are not well understood in part because of methodological difficulties in creating site-specific DPCs. Here, a strategy for obtaining site-specific DPCs is presented, and in vitro interactions of the Escherichia coli nucleotide excision repair (NER) UvrABC nuclease at sites of DPCs are investigated. To create site-specific DPCs, the catalytic chemistry of the T4 pyrimidine dimer glycosylase͞apurinic͞apyrimidinic site lyase (T4-pdg) has been exploited, namely, its ability to be covalently trapped to apurinic͞apyrimidinic sites within duplex DNA under reducing conditions. Incubation of the DPCs with UvrABC proteins resulted in DNA incision at the 8th phosphate 5 and the 5th and 6th phosphates 3 to the protein-adducted site, generating as a major product of the reaction a 12-mer DNA fragment crosslinked with the protein. The incision occurred only in the presence of all three protein subunits, and no incisions were observed in the nondamaged complementary strand. The UvrABC nuclease incises DPCs with a moderate efficiency. The proper assembly and catalytic function of the NER complex on DNA containing a covalently attached 16-kDa protein suggest that the NER pathway may be involved in DPC repair and that at least some subset of DPCs can be removed by this mechanism without prior proteolytic degradation.I n cells, DNA is tightly associated with a variety of proteins that serve both to maintain the structural organization of the genetic material and to coordinate cellular processes including replication, repair, recombination, and transcription. Many endogenous compounds (e.g., metabolites of lipid peroxidation) as well as environmental agents are reactive with both DNA and proteins and thus can produce covalent linkage between these two types of macromolecules (1-13). DNA-protein crosslinks (DPCs) represent a relatively abundant form of DNA damage as evidenced by data indicating that the background level of DPCs in human white blood cells ranged from 0.5 to 4.5 per 10 7 bases (1). An age-related accumulation of DPCs has also been observed in mouse organs (2), supporting the hypothesis that oxidative mechanisms contribute to the formation of these DNA damages (2, 3). DPC levels increase dramatically upon exposure to a variety of physical or chemical agents, including UV light (4), ionizing radiation (5), ␤-propiolactone (6), aldehydes (1, 7-9), arsenite (10), ferric nitrilotriacetate (11), chromate (12), nickel (13), and others. Chemotherapeutic agents, such as cisplatin (12,14), bisplatinum (15), and neocarcinostatin (16), have also been shown to induce DPC formation. Exposure to several DPC-inducing agents gives rise to genotoxic and carcinogenic effects, and for some agents, such as formaldehyde, their primary mutagenic effects are believed to be mediated through the ...

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confidence: 61%

mentioning

confidence: 99%

Incision of DNA–protein crosslinks by UvrABC nuclease suggests a potential repair pathway involving nucleotide excision repair

Minko

Zou

Lloyd

2002

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

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“…Bis-aldehydes are another category of important short-chain oxidation products and, like the α,β-substituted-alkenals, they are bifunctional and have the potential to crosslink proteins and DNA [60]. Probably the best known is the 3-carbon molecule malondialdehyde (MDA), as it is a very commonly used marker of lipid peroxidation in biological and clinical samples [61,62], although it has also been much criticized in this respect.…”

Section: Alkanalsmentioning

confidence: 99%

Chemistry and analysis of HNE and other prominent carbonyl-containing lipid oxidation compounds

Sousa

Pitt

Spickett

2017

Free Radical Biology and Medicine

145

105

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The process of lipid oxidation generates a diverse array of small aldehydes and carbonyl-containing compounds, which may occur in free form or esterified within phospholipids and cholesterol esters. These aldehydes mostly result from fragmentation of fatty acyl chains following radical oxidation, and the products can be subdivided into alkanals, alkenals (usually D,β-unsaturated), γ-substituted alkenals and bis-aldehydes.Isolevuglandins are non-fragmented di-carbonyl compounds derived from H 2 -isoprostanes, and oxidation of the ω-3-fatty acid docosahexenoic acid yield analogous 22 carbon neuroketals. Non-radical oxidation by hypochlorous acid can generate D-chlorofatty aldehydes from plasmenyl phospholipids. Most of these compounds are reactive and have generally been considered as toxic products of a deleterious process. The reactivity is especially high for the D,β-unsaturated alkenals, such as acrolein and crotonaldehyde, and for γ-substituted alkenals, of which 4-hydroxy-2-nonenal and 4-oxo-2-nonenal are best Page | 2 known. Nevertheless, in recent years several previously neglected aldehydes have been investigated and also found to have significant reactivity and biological effects; notable examples are 4-hydroxy-2-hexenal and 4-hydroxy-dodecadienal. This has led to substantial interest in the biological effects of all of these lipid oxidation products and their roles in disease, including proposals that HNE is a second messenger or signalling molecule.However, it is becoming clear that many of the effects elicited by these compounds relate to their propensity for forming adducts with nucleophilic groups on proteins, DNA and specific phospholipids. This emphasizes the need for good analytical methods, not just for free lipid oxidation products but also for the resulting adducts with biomolecules. The most informative methods are those utilizing HPLC separations and mass spectrometry, although analysis of the wide variety of possible adducts is very challenging. Nevertheless, evidence for the occurrence of lipid-derived aldehyde adducts in biological and clinical samples is building, and offers an exciting area of future research. AbbreviationsAcr-dG, 1,N2-propanodeoxyguanosine; AGEs, advanced glycation end-product; ALEs, advanced lipoxidation end product; ApoB100, apolipoprotein B100; ApoE, apolipoprotein E; ARP, aldehyde reactive probe; AspN, endoproteinase AspN (flavastacin); βLG, β-lactoglobulin; BHZ, biotin hydrazide; BN-PAGE, blue native polyacrylamide gel

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“…Voitkun and Zhitkovich reported that MDA created cruciate bonds with DNA and proteins. This potential of MDA with genotoxic activities may cause both mutations and cancer (13). In vitro studies have shown that ACR decreases the glutathione (GSH) content (14).…”

Section: Introductionmentioning

confidence: 99%

The protective effect of N-acetylcysteine against acrylamide toxicity in liver and small and large intestine tissues

Altınöz¹,

Türköz²,

Vardı³

2015

BLL

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Abstract:The aim of this study was to investigate the protective effects of N-acetylcysteine against acrylamide toxicity in liver and small and large intestine tissues in rats. The rats were divided into four groups. Acrylamide administration increased MDA levels in all tissues significantly (p < 0.05). But acrylamide+NAC administration decreased MDA levels signifi cantly as compared to the acrylamide group, and lowered it to a level close to the control group values (p < 0.05). GSH levels in liver and small intestine tissues reduced signifi cantly in the acrylamide group (p < 0.05). But acrylamide+NAC administration increased GSH levels signifi cantly in all tissues. Whereas GST activity decreased signifi cantly in the acrylamide group in liver and small intestine tissues as compared to the other groups (p < 0.05), the GST activity increased signifi cantly in the acrylamide+NAC group in all tissues as compared to the acrylamide group (p < 0.05). Liver histopathology showed that the liver epithelial cells were damaged signifi cantly in the acrylamide group. Small intestine histopathology showed that the intestinal villous epithelial cells were damaged signifi cantly in the acrylamide group. Our results indicate that a high level of acrylamide causes oxidative damage in liver and small and large intestine tissues, while N-acetylcysteine administration in a pharmacological dose shows to have an antioxidant effect in preventing this damage (Tab. 2, Fig. 2, Ref. 66). Text in PDF www.elis.sk.

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Analysis of DNA–protein crosslinking activity of malondialdehyde in vitro

Cited by 101 publications

References 38 publications

Incision of DNA–protein crosslinks by UvrABC nuclease suggests a potential repair pathway involving nucleotide excision repair

Incision of DNA–protein crosslinks by UvrABC nuclease suggests a potential repair pathway involving nucleotide excision repair

Chemistry and analysis of HNE and other prominent carbonyl-containing lipid oxidation compounds

The protective effect of N-acetylcysteine against acrylamide toxicity in liver and small and large intestine tissues

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