Radical Scavenging Properties of Tryptophan Metabolites

Goda, Katalin; Hamane, Y.; Kishimoto, Ritsuko; Ogishi, Yasuka

doi:10.1007/978-1-4615-4709-9_50

Cited by 59 publications

(49 citation statements)

References 9 publications

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“…While our data do not show a direct cause and effect relationship between IDO activity and oxidative damage, our results are consistent with the postulate that IDO activity may have an antioxidant function [11,[25][26][27]. IDO activity could mitigate oxidative damage by multiple mechanisms: (1) consuming superoxide anions [68,69], which should limit the formation of other ROS; (2) generating downstream products, including 3-hydroxykynurenine and 3-hydroxyanthranilic acid, which are free radical scavengers [11,26,70,71]; (3) increasing cellular NAD levels, which indirectly helps to maintain cell viability [72,73]. RAW 264.7 macrophages probably possess the enzymes required make 3-hydroxykynurenine, 3-hydroxyanthranilic acid and NAD [73,74]; therefore, we cannot dismiss the potential contribution of those molecules to the apparent antioxidant effect of IDO.…”

Section: Discussionsupporting

confidence: 87%

Decreased protein nitration in macrophages that overexpress indoleamine 2, 3-dioxygenase

Keskin

Marshall

Munn

et al. 2007

Cellular and Molecular Biology Letters

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Abstract:The activity of indoleamine 2, 3-dioxygenase (IDO; E.C. 1.13.11.42) catalyzes the oxidative cleavage of tryptophan to form kynurenine. IDO activity consumes superoxide anions; therefore, we postulated that over-expression of IDO might mitigate superoxide-anion dependent, oxidative modification of cellular proteins in vitro. We prepared and characterized RAW 264.7 macrophages that were stably transfected with either an IDO expression vector or the control (empty) vector. We detected IDO mRNA, protein, and enzyme activity in the IDO-transfected macrophages, but not in the macrophages transfected with the empty vector. To generate superoxide anions in situ, we treated the IDO-and control-transfected cultures with xanthine or hypoxanthine, and then used ELISA methods to quantitate the relative levels of oxidatively modified proteins in total cell lysates. The levels of protein carbonyls were similar in IDO-transfected and vector-transfected macrophages; however, protein nitration was significantly less in IDO-transfected cells compared to control transfectants. In addition, steady-state levels of superoxide anions were significantly lower in the IDO-transfected cultures compared with control transfectants. Our results are consistent with the concept that, besides degrading tryptophan, IDO activity may protect cells from oxidative damage.

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Section: Discussionsupporting

confidence: 87%

Decreased protein nitration in macrophages that overexpress indoleamine 2, 3-dioxygenase

Keskin

Marshall

Munn

et al. 2007

Cellular and Molecular Biology Letters

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“…Note that both LIS and SAL have nonvascular effects. LIS acts as a weak antioxidant and nitric oxide scavenger (40). However, it is unlikely that these effects are manifest with the dose of 0.3 mg/kg used in this study.…”

Section: Discussionmentioning

confidence: 86%

Low-Dose Poly(ADP-Ribose) Polymerase Inhibitor-Containing Combination Therapies Reverse Early Peripheral Diabetic Neuropathy

Drel

Szabó

et al. 2005

Diabetes

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Poly(ADP-ribose) polymerase (PARP) inhibition has recently been identified as a novel approach to treatment of experimental peripheral diabetic neuropathy (PDN). (5); 2) changes in transcriptional regulation and gene expression (5-7); and 3) poly-(ADP-ribosyl)ation and resulting inhibition of the glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase, with concomitant activation of several major pathogenetic mechanisms, i.e., nonenzymatic glycation, protein kinase C, and hexosamine pathway (2). Using a pharmacological approach with several structurally unrelated PARP inhibitors as well as PARP-deficient mice, we have recently discovered the key role of PARP in the development of early peripheral diabetic neuropathy (PDN) (3,8). Note that PARP inhibitors administered in doses resulting in complete or almost complete PARP inhibition in the diabetic peripheral nerve (3,8) appeared at least 100-fold more effective in correcting nerve conduction slowing, NAD ϩ /NADH redox imbalances, energy failure, and neurovascular dysfunction than conventional antioxidants (9,10).A recent 9-month PARP inhibitor study in the streptozotocin (STZ)-induced diabetic rat model did not reveal clearly manifest side effects (4), and PARP Ϫ/Ϫ mice do not develop obvious phenotypic changes (5). However, the long-term consequences of complete PARP inhibition in pathological conditions associated with oxidative stress, including diabetes, are unclear and can hardly be sorted out in rodents because of their limited life span. Diabetesassociated oxidative stress leads to DNA damage, e.g., in the peripheral nervous system (11), and PARP activation is an important mechanism of DNA repair (5). Therefore, it is reasonable to suggest that 1) complete PARP inhibition can potentially result in premature aging and 2) targeted delivery of PARP-1 antisense oligodeoxynucleotide-containing vectors (12) or PARP-1 RNA interference (RNAi) (13), rather than pharmacological PARP inhibition, should be considered as a future therapy of PDN (1). However, it is unlikely that such approaches will be available in clinical practice in the near future. An alternative strategy would be to develop low-dose PARP inhibitor-containing combination therapies with other agents already used in clinical practice and proven to be effective in the treatment

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“…Oral trp administration has been shown to increase serotonin concentrations in the plasma and brain (Leathwood and Fernstrom, 1990;Adeola and Ball, 1992;Henry et al, 1992), and to accelerate gastric emptying rate (Ponter et al, 1994) and digesta passage rate. Also, trp and several of its derivatives from the kynurenine pathway as well as serotonin and melatonin biosynthesis pathways, may function as free-radical scavengers and antioxidants (Goda et al, 1999;Watanabe et al, 2002). Therefore, trp utilization may be increased to satisfy inflammation and general body defense requirements as trp is the only indispensable amino acid for which plasma concentrations are significantly decreased during an immune challenge (Melchior et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Bioavailability of threonine and tryptophan in peanut meal for starter pigs using slope-ratio assay

Adeola

2009

Animal

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The objective of the two studies was to determine the bioavailability of threonine (thr) and tryptophan (trp) in peanut meal, relative to L-thr and L-trp, for starter pigs using the slope-ratio bioassay. Basal diets (BDs) contained surfeit amounts of all amino acids for 10 to 20 kg pigs, except for thr (Experiment 1) or trp (Experiment 2). In the first study, four reference diets were formulated by supplementing the BD with 0, 0.4, 0.8 or 1.2 g of L-thr/kg at the expense of cornstarch; two test diets were formulated by replacing cornstarch in the BD with peanut meal at 32 or 64 g/kg of diet to supply 0.4 or 0.8 g thr/kg, respectively. Four reference diets consisting of the BD supplemented with 0, 0.15, 0.3 or 0.45 g of L-trp/kg at the expense of cornstarch and two test diets in which cornstarch in the BD was replaced with peanut meal at 30 or 60 g/kg of diet to supply 0.14 or 0.28 g trp/kg, respectively were used in the second study. Body weight gain responded in a linear way to supplemental L-thr or thr from peanut meal ( P , 0.001). There was a linear response ( P , 0.001) to thr supplementation from L-thr or peanut meal in gain-to-feed ratio. The addition of trp to the BD linearly increased ( P , 0.05) body weight gain, feed intake and gainto-feed ratio regardless of the trp source. Common-intercept, multiple linear regression in slope-ratio methodology using weight gain or gain-to-feed ratio as dependent variables and supplemental thr intake as independent variable gave relative bioavailability estimates of 71.9% or 75.7%, respectively. Corresponding values for trp were 92% and 75.7%. The fiducial limits for none of the relative bioavailability estimates included 100%. The data from these studies suggest that the bioavailabilities of thr and trp in peanut meal are less than those of L-thr and L-trp, and that the bioavailabilities of thr and trp in peanut meal are 72% to 76% and 76% to 92%, respectively.

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Radical Scavenging Properties of Tryptophan Metabolites

Cited by 59 publications

References 9 publications

Decreased protein nitration in macrophages that overexpress indoleamine 2, 3-dioxygenase

Decreased protein nitration in macrophages that overexpress indoleamine 2, 3-dioxygenase

Low-Dose Poly(ADP-Ribose) Polymerase Inhibitor-Containing Combination Therapies Reverse Early Peripheral Diabetic Neuropathy

Bioavailability of threonine and tryptophan in peanut meal for starter pigs using slope-ratio assay

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