Nitration and chlorination of folic acid by peroxynitrite and hypochlorous acid, and the selective binding of 10-nitro-folate to folate receptor β

Nakamura, Motoyuki; Nagayoshi, Ryusaku; Ijiri, Kosei; Nakashima-Matsushita, Noriko; Takeuchi, Kosei; Matsuyama, Tomohiko

doi:10.1016/s0006-291x(02)02359-8

Cited by 13 publications

(11 citation statements)

References 31 publications

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“…Another study [11] indicated that the side chain, i.e. N ‐( p ‐aminobenzoyl)‐ L ‐glutamic acid, is more important, since the products formed by nitration of FA were identified as 10‐nitrofolate and 12‐nitrofolate [11]. The present study was designed to further examine the antioxidant activity of FA and its physiological metabolites and to determine which part of the molecule is important for this activity.…”

Section: Introductionmentioning

confidence: 97%

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Tetrahydrofolate and 5‐methyltetrahydrofolate are folates with high antioxidant activity. Identification of the antioxidant pharmacophore

et al. 2003

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The presumed protective e¡ect of folic acid on the pathogenesis of cardiovascular, hematological and neurological diseases and cancer has been associated with the antioxidant activity of folic acid. Peroxynitrite (PON) scavenging activity and inhibition of lipid peroxidation (LPO) of the physiological forms of folate and of structurally related compounds were tested. It was found that the fully reduced forms of folate, i.e. tetrahydrofolate (THF) and 5-methyltetrahydrofolate (5-MTHF), had the most prominent antioxidant activity. It appeared that their protection against LPO is less pronounced than their PON scavenging activity. The antioxidant activity of these forms of folic acid resides in the pterin core, the antioxidant pharmacophore is 4-hydroxy-2,5,6-triaminopyrimidine. It is suggested that an electron donating e¡ect of the 5-amino group is of major importance for the antioxidant activity of 4-hydroxy-2,5,6-triaminopyrimidine. A similar electron donating e¡ect is probably important for the antioxidant activity of THF and 5-MTHF.

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Section: Introductionmentioning

confidence: 97%

“…One study [10] suggested that the 4‐OH group on the pterin ring has an important role. Another study [11] indicated that the side chain, i.e. N ‐( p ‐aminobenzoyl)‐ L ‐glutamic acid, is more important, since the products formed by nitration of FA were identified as 10‐nitrofolate and 12‐nitrofolate [11].…”

Section: Introductionmentioning

confidence: 99%

Tetrahydrofolate and 5‐methyltetrahydrofolate are folates with high antioxidant activity. Identification of the antioxidant pharmacophore

et al. 2003

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“…Reactive oxygen species (ROS) including superoxide radicals can be produced from various sources including mitochondrial electron transport chain (ETC) and other cellular enzymes such as NADPH oxidase and myeloperoxidase or eosinophil oxidase in immune cells (i.e., macrophage cells and neutrophils), ethanol-inducible cytochrome P450 2E1 (CYP2E1) and CYP4A isozymes in endoplasmic reticulum (ER), cytosolic xanthine oxidase, and so forth [12–19]. RNS not only interact with Tyr, but also with tryptophan (Trp) [20], lipids [21], and vitamins [22, 23]. Thus, the nitrative modifications of target proteins, DNA, lipids, and vitamins, usually contributing to alterations of their normal functions and the development or progression of tissue injury [4, 24, 25].…”

Section: Introductionmentioning

confidence: 99%

Functional Roles of Protein Nitration in Acute and Chronic Liver Diseases

Abdelmegeed

Song

2014

Oxidative Medicine and Cellular Longevity

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Nitric oxide, when combined with superoxide, produces peroxynitrite, which is known to be an important mediator for a number of diseases including various liver diseases. Peroxynitrite can modify tyrosine residue(s) of many proteins resulting in protein nitration, which may alter structure and function of each target protein. Various proteomics and immunological methods including mass spectrometry combined with both high pressure liquid chromatography and 2D PAGE have been employed to identify and characterize nitrated proteins from pathological tissue samples to determine their roles. However, these methods contain a few technical problems such as low efficiencies with the detection of a limited number of nitrated proteins and labor intensiveness. Therefore, a systematic approach to efficiently identify nitrated proteins and characterize their functional roles is likely to shed new insights into understanding of the mechanisms of hepatic disease pathophysiology and subsequent development of new therapeutics. The aims of this review are to briefly describe the mechanisms of hepatic diseases. In addition, we specifically describe a systematic approach to efficiently identify nitrated proteins to study their causal roles or functional consequences in promoting acute and chronic liver diseases including alcoholic and nonalcoholic fatty liver diseases. We finally discuss translational research applications by analyzing nitrated proteins in evaluating the efficacies of potentially beneficial agents to prevent or treat various diseases in the liver and other tissues.

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“…Expression of FR-β in normal tissues is restricted to placenta and hematopoietic cells, where it is expressed in the myelomonocytic lineage with an increase in its level of expression during neutrophil maturation or monocyte/macrophage activation (Ross et al, 1999; Nakashima-Matsushita et al, 1999). However, FR-β in neutrophils are unable to bind folate due to aberrant post-translational modifications (Nakamura et al, 2002). FR-β is expressed in approximately 70% of the cases of acute AML blast cells and is frequently co-expressed with CD34 (Pan et al, 2002), a common marker used to enriched populations of human hematopoietic stem cells (HSCs) and progenitors.…”

Section: Introductionmentioning

confidence: 99%

Targeting human clonogenic acute myelogenous leukemia cells via folate conjugated liposomes combined with receptor modulation by all-trans retinoic acid

Piao

et al. 2010

International Journal of Pharmaceutics

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Our previous data demonstrated that folate receptor β (FR-β) targeted liposomal doxorubicin (FT-L-DOX) showed enhanced cytotoxicity relative to non-targeted liposomal doxorubicin (CON-L-DOX), and the effect was enhanced by selective FR-β upregulation by all-trans retinoic acid (ATRA) in AML blast cells. In this study, the enhanced cytotoxicity was investigated in the proliferating human AML clonogenic cells by combining FT-L-DOX with ATRA. Also, pharmacokinetic properties by pretreatment of ATRA were evaluated using FR-targeted liposomal calcein (FT-L-Calcein). Pharmacokinetic study showed that the area under the concentration curve (AUC) of FT-L-Calcein was decreased and total clearance was increased by pretreatment with ATRA. Meanwhile, the volume of distribution was significantly increased by pretreatment of ATRA. Moreover, calcein level in the liver, spleen and kidney was increased following intravenous administration of FT-L-Calcein by pretreatment of ATRA. In vitro cytotoxicity of FT-L-DOX was higher than that of CON-L-DOX and was increased by pretreatment with ATRA. Colony formation in AML cells was lower due to treatment with FT-L-DOX compared with CON-L-DOX and colony formation further decreased upon pretreatment with ATRA. Moreover, FT-L-DOX was more toxic to AML clonogenic cells than to AML blast cells. The results demonstrate that the efficiency of FR-mediated targeting of FT-L-DOX was preferentially enhanced by ATRA induced FR-β upregulation in AML clonogenic cells.

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Nitration and chlorination of folic acid by peroxynitrite and hypochlorous acid, and the selective binding of 10-nitro-folate to folate receptor β

Cited by 13 publications

References 31 publications

Tetrahydrofolate and 5‐methyltetrahydrofolate are folates with high antioxidant activity. Identification of the antioxidant pharmacophore

Tetrahydrofolate and 5‐methyltetrahydrofolate are folates with high antioxidant activity. Identification of the antioxidant pharmacophore

Functional Roles of Protein Nitration in Acute and Chronic Liver Diseases

Targeting human clonogenic acute myelogenous leukemia cells via folate conjugated liposomes combined with receptor modulation by all-trans retinoic acid

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