Ornithine decarboxylase deficiency critically impairs nitrogen metabolism and survival in Aedes aegypti mosquitoes.
Ornithine decarboxylase deficiency critically impairs nitrogen metabolism and survival in Aedes aegypti mosquitoes.
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DOI：
10.1096/fj.202200008r
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发表时间：
2022-05
期刊：
影响因子：
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通讯作者：
Scaraffia PY
中科院分区：
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作者：
Isoe J;Petchampai N;Joseph V;Scaraffia PY
鸟氨酸脱羧酶（ODC; EC 4.1.1.17）催化鸟氨酸转化为腐胺，腐胺是多胺从头生物合成的限速第一步。以前，我们报道了黄嘌呤脱氢酶1（XDH 1）的基因敲除-一个基因编码的酶参与尿酸合成的最后两个步骤-导致ODC转录水平的增加，在埃及伊蚊的血喂养蚊子的脂肪体，这表明在氮处理过程中XDH 1和ODC之间的分子水平的串扰。为了进一步研究ODC在氮代谢中的作用，我们在糖和血液喂养的Ae中进行了几项生化和遗传分析。埃及女性。不同的ODC基因和蛋白质的表达模式中观察到的蚊子组织解剖在第一gonotrophic周期。药理学和RNA干扰介导的敲低ODC对蚊子的存活产生负面影响，破坏氮废物的处理，延迟产卵开始，并降低卵黄生成吸血雌性的繁殖力。两个主要的消化丝氨酸蛋白酶的表达滞后，减少血餐消化中肠，并减少卵黄蛋白原卵黄蛋白的吸收在卵巢卵泡中观察到蛋白质印迹法在ODC缺陷的女性。此外，ODC的基因沉默显示了广泛的转录调控基因编码的蛋白质参与蚊子脂肪体，中肠和马氏管吸血前后的多个代谢途径。总之，这些数据表明，ODC在蚊子代谢中起着至关重要的作用，并且ODC与多个基因和蛋白质交叉交谈，以防止Ae中致命的氮扰动。埃及女性。
Ornithine decarboxylase (ODC; EC 4.1.1.17) catalyzes the conversion of ornithine to putrescine, the rate-limiting first step for de novo polyamine biosynthesis. Previously, we reported that genetic knockdown of xanthine dehydrogenase 1 (XDH1) - a gene encoding the enzyme involved in the last two steps of uric acid synthesis - causes an increase of ODC transcript levels in fat body of blood-fed Aedes aegypti mosquitoes, suggesting a crosstalk at molecular level between XDH1 and ODC during nitrogen disposal. To further investigate the role of ODC in nitrogen metabolism, we conducted several biochemical and genetic analyses in sugar- and blood-fed Ae. aegypti females. Distinct ODC gene and protein expression patterns were observed in mosquito tissues dissected during the first gonotrophic cycle. Both pharmacological and RNA interference-mediated knockdown of ODC negatively impacted mosquito survival, disrupted nitrogen waste disposal, delayed oviposition onset, and decreased fecundity in vitellogenic blood-fed females. A lag in the expression of two major digestive serine proteases, a reduction of blood meal digestion in the midgut, and a decrease of vitellogenin yolk protein uptake in ovarian follicles were observed by western blots in ODC-deficient females. Moreover, genetic silencing of ODC showed a broad transcriptional modulation of genes encoding proteins involved in multiple metabolic pathways in mosquito fat body, midgut and Malpighian tubules prior to and after blood feeding. All together, these data demonstrate that ODC plays an essential role in mosquito metabolism, and that ODC cross-talks with multiple genes and proteins to prevent deadly nitrogen perturbations in Ae. aegypti females.