A Drosophila model for the screening of bioavailable NADPH oxidase inhibitors and antioxidants
A Drosophila model for the screening of bioavailable NADPH oxidase inhibitors and antioxidants
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DOI：
10.1007/s11010-011-0743-3
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发表时间：
2011-02
影响因子：
4.3
通讯作者：
N. Anh;Maiko Nishitani;S. Harada;M. Yamaguchi;K. Kamei
中科院分区：
文献类型：
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作者：
N. Anh;Maiko Nishitani;S. Harada;M. Yamaguchi;K. Kamei
NADPH氧化酶是非线粒体细胞活性氧（ROS）的主要来源，也是包括动脉粥样硬化和高血压在内的多种疾病的主要原因。为了筛选抑制NADPH氧化酶活性的新型治疗试剂，我们开发了过表达NADPH氧化酶家族成员人双氧化酶2 （hDuox2）的黑胃果蝇作为筛选模型。这些果蝇（GMR-GAL4/UAS-hDuox2）在眼盘后区具有高ROS生成以及易于识别的粗糙眼表型，这是进一步筛选步骤的理想和方便的标记。此外，hduox2诱导的糙眼表型可以通过饲喂含有桑叶（MLs）的培养基来恢复，据报道桑叶具有抗代谢作用。一些商业上可用的抗氧化剂，如槲皮素-3- o -d-葡萄糖苷或槲皮素-3- o -葡萄糖-6 ' -醋酸酯，或MLs和其他草药中含有的柚皮素，也显示出对糙眼表型的类似抑制作用。我们的研究结果表明，黄酮类苷从肠道吸收，并在体内发挥作用。就像在大鼠等哺乳动物模型中一样。因此，GMR-GAL4/UAS-hDuox2蝇系是筛选NADPH氧化酶抑制剂和/或抗氧化剂等新药的有希望的模型。
NADPH oxidase is the major source of non-mitochondrial cellular reactive oxygen species (ROS), and also is reported to be a major cause of various diseases including atherosclerosis and hypertension. In order to screen a new curative reagent that can suppress NADPH oxidase activity, we developed aDrosophila melanogasterfly that would overexpress human Dual oxidase 2 (hDuox2), a member of the NADPH oxidase family, as a screening model. These flies (GMR-GAL4/UAS-hDuox2) had a high generation of ROS in the posterior region of the eye discs along with an easily recognizable rough-eye phenotype, which is an ideal and convenient marker for further screening steps. Moreover, the hDuox2-induced rough-eye phenotype can be rescued by feeding with a culture medium containing mulberry leaves (MLs), which reportedly have an antimetabolic effect. Some commercially available antioxidants such as quercetin-3-O-d-glucoside or quercetin-3-O-glucose-6′′-acetate, or the naringin contained in MLs and other herbs, also have shown a similar suppressing effect on the rough-eye phenotype. Our results suggest that flavonoid glycoside is absorbed from the intestine and functions in the body ofD. melanogasteras it does in mammalian models such as rats. Thus, the GMR-GAL4/UAS-hDuox2 fly line is a promising model for the screening of novel drugs such as NADPH oxidase inhibitors and/or antioxidants.