A Drosophila model for the screening of bioavailable NADPH oxidase inhibitors and antioxidants

Anh, Nguyen Thi Tu; Nishitani, Maiko; Harada, Shigeharu; Yamaguchi, Masamitsu; Kamei, Kaeko

doi:10.1007/s11010-011-0743-3

Cited by 11 publications

(12 citation statements)

References 21 publications

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“…This gene is potentially functional where it is present and probably produces ROS in the form of hydrogen peroxide. Important insect specific functions were described for NOXes such as cuticular hardening [70, 71], wound healing [72, 73], smooth muscle contraction [74] and gut immunity [34, 75–77]. NOX4-art could have an arthropod specific function as well and therefore be an interesting target for new vector and pest control strategies.…”

Section: Discussionmentioning

confidence: 99%

Evolutionary origin and function of NOX4-art, an arthropod specific NADPH oxidase

et al. 2017

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BackgroundNADPH oxidases (NOX) are ROS producing enzymes that perform essential roles in cell physiology, including cell signaling and antimicrobial defense. This gene family is present in most eukaryotes, suggesting a common ancestor. To date, only a limited number of phylogenetic studies of metazoan NOXes have been performed, with few arthropod genes. In arthropods, only NOX5 and DUOX genes have been found and a gene called NOXm was found in mosquitoes but its origin and function has not been examined. In this study, we analyzed the evolution of this gene family in arthropods. A thorough search of genomes and transcriptomes was performed enabling us to browse most branches of arthropod phylogeny.ResultsWe have found that the subfamilies NOX5 and DUOX are present in all arthropod groups. We also show that a NOX gene, closely related to NOX4 and previously found only in mosquitoes (NOXm), can also be found in other taxonomic groups, leading us to rename it as NOX4-art. Although the accessory protein p22-phox, essential for NOX1-4 activation, was not found in any of the arthropods studied, NOX4-art of Aedes aegypti encodes an active protein that produces H2O2. Although NOX4-art has been lost in a number of arthropod lineages, it has all the domains and many signature residues and motifs necessary for ROS production and, when silenced, H2O2 production is considerably diminished in A. aegypti cells.ConclusionsCombining all bioinformatic analyses and laboratory work we have reached interesting conclusions regarding arthropod NOX gene family evolution. NOX5 and DUOX are present in all arthropod lineages but it seems that a NOX2-like gene was lost in the ancestral lineage leading to Ecdysozoa. The NOX4-art gene originated from a NOX4-like ancestor and is functional. Although no p22-phox was observed in arthropods, there was no evidence of neo-functionalization and this gene probably produces H2O2 as in other metazoan NOX4 genes. Although functional and present in the genomes of many species, NOX4-art was lost in a number of arthropod lineages.Electronic supplementary materialThe online version of this article (doi:10.1186/s12862-017-0940-0) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Evolutionary origin and function of NOX4-art, an arthropod specific NADPH oxidase

et al. 2017

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“…Longevity assays are one of the most simple and efficient methodological approaches to evaluate the aging and anti-aging effects of simple compounds and complex mixtures on higher organisms. D. melanogaster is considered a very useful genetic model on aging research since its similarities with human metabolic pathways controlling nutrient uptake, storage, and metabolism [89,90]. In addition, this model has a short lifespan compared with similar in vivo models, which reduces the experimental periods.…”

Section: Discussionmentioning

confidence: 99%

Nutraceutic Potential of Two Allium Species and Their Distinctive Organosulfur Compounds: A Multi-Assay Evaluation

Fernández-Bedmar

Demyda-Peyrás

Merinas-Amo

et al. 2019

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This study aimed to evaluate the biological activities of two Allium species (garlic and onion) as well as diallyl disulphide (DADS) and dipropyl disulphide (DPDS) as their representative bioactive compounds in a multi-assay experimental design. The genotoxic, antigenotoxic, and lifespan effects of garlic, onion, DADS, and DPDS were checked in Drosophila melanogaster and their cytotoxic, pro-apoptotic, and DNA-clastogenic activities were analyzed using HL60 tumoral cells. All compounds were non-genotoxic and antigenotoxic against H2O2-induced DNA damage with a positive dose-response effect and different inhibition percentages (the highest value: 95% for DADS) at all tested concentrations. Daily intake of Allium vegetables, DADS, or DPDS had no positive effects on flies’ lifespan and health span. Garlic and DADS exerted the highest cytotoxic effects in a positive dose-dependent manner. Garlic and DADS exerted a DNA-internucleosomal fragmentation as an index of induced proapoptotic activity on HL60 cells. Allium vegetables and DADS were able to induce clastogenic strand breaks in the DNA of HL60 cells. This study showed the genomic safety of the assayed substances and their protective genetic effects against the hydrogen peroxide genotoxine. Long-term treatments during the whole life of the Drosophila genetic model were beneficial only at low-median concentrations. The chemo-preventive activity of garlic could be associated with its distinctive organosulfur DADS. We suggest that supplementary studies are needed to clarify the cell death pathway against garlic and DADS.

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“…In vivo: Naringin (3 % fed to flies in culture medium) has been shown to inhibit the protein hDuox2, a member of the NADPH oxidase family, in a GMR-GAL4/UAS-hDuox2 fly line screening model, thereby implicating a strong antioxidant potential through inhibition of ROS [68]. The same antioxidant potential of dietary naringin (1.5-3.0 g/kg) was responsible for decreased serum triacylglycerol levels in fish oil supplemented fattening lambs [69].…”

Section: Antioxidant Effectmentioning

confidence: 99%

Preclinical Evidence for the Pharmacological Actions of Naringin: A Review

et al. 2014

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Abstract! Naringin, chemically 4′,5,7-trihydroxyflavanone-7-rhamnoglucoside, is a major flavanone glycoside obtained from tomatoes, grapefruits, and many other citrus fruits. It has been experimentally documented to possess numerous biological properties such as antioxidant, anti-inflammatory, and antiapoptotic activities. In vitro and in vivo studies have further established the usefulness of naringin in various preclinical models of atherosclerosis, cardiovascular disorders, diabetes mellitus, neurodegenerative disorders, osteoporosis, and rheumatological disorders. Apart from this, naringin has also exerted chemopreventive and anticancer attributes in various models of oral, breast, colon, liver, lung, and ovarian cancer. This wide spectrum of biological expediency has been documented to be a result of either the upregulation of various cell survival proteins or the inhibition of inflammatory processes, or a combination of both. Due to the scarcity of human studies on naringin, this review focuses on the various established activities of naringin in in vitro and in vivo preclinical models, and its potential therapeutic applications using the available knowledge in the literature. Additionally, it also encompasses the pharmacokinetic properties of naringin and its inhibition of CYP isoenzymes, and the subsequent drug interactions. Moreover, further clinical research is evidently needed to provide significant insights into the mechanisms underlying the effects of naringin in humans.

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A Drosophila model for the screening of bioavailable NADPH oxidase inhibitors and antioxidants

Cited by 11 publications

References 21 publications

Evolutionary origin and function of NOX4-art, an arthropod specific NADPH oxidase

Evolutionary origin and function of NOX4-art, an arthropod specific NADPH oxidase

Nutraceutic Potential of Two Allium Species and Their Distinctive Organosulfur Compounds: A Multi-Assay Evaluation

Preclinical Evidence for the Pharmacological Actions of Naringin: A Review

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