Mifepristone/RU486 acts in Drosophila melanogaster females to counteract the life span-shortening and pro-inflammatory effects of male Sex Peptide.
Mifepristone/RU486 acts in Drosophila melanogaster females to counteract the life span-shortening and pro-inflammatory effects of male Sex Peptide.
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米非司酮/RU486 在雌性黑腹果蝇中发挥作用，抵消雄性性肽的寿命缩短和促炎作用
DOI：
10.1007/s10522-017-9703-y
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发表时间：
2017-06
期刊：
影响因子：
4.5
通讯作者：
Song J
中科院分区：
文献类型：
--
作者：
Tower J;Landis GN;Shen J;Choi R;Fan Y;Lee D;Song J
将性肽（SP）基因零突变的雄性与野生型雄性进行比较，研究其引起雌性生理变化的能力，这些生理变化可以通过米非司酮逆转。野生型菌株的雄株平均使雌株平均寿命减少-51%。喂食米非司酮可使这些雌性的寿命平均增加106%。相比之下，sp为零的雄性没有降低雌性的寿命，米非司酮使这些雌性的中位寿命平均增加了+14%，这与米非司酮对处女雌性的影响相当（平均+16%）。先天免疫应答转基因报告基因（Drosocin-GFP）在雌性与野生型雄性交配时表达增加，而米非司酮降低了这种表达。相比之下，sp缺失的雄鼠没有增加雌鼠中Drosocin-GFP报告基因的表达。同样，交配增加了内源性微生物负荷，而在喂食米非司酮的雌性和与sp为零的雄性交配的雌性中，这种影响减少或不存在；染料泄漏试验未发现肠屏障完整性丧失。用强力霉素处理成蝇，减少微生物负荷，降低交配和米非司酮对寿命的影响。最后，米非司酮阻断了转基因SP在处女雌性中对寿命的负面影响。这些数据支持了雄性SP对雌性动物的缩短寿命、免疫抑制和促炎作用的结论，并证明了米非司酮在雌性动物中的作用可以抵消雄性SP的这些作用。
Males with null mutation of Sex Peptide (SP) gene were compared to wild-type males for the ability to cause physiological changes in females that could be reversed by mifepristone. Males from wild-type strains decreased median female life span by average -51%. Feeding mifepristone increased life span of these females by average +106%. In contrast, SP-null males did not decrease female life span, and mifepristone increased median life span of these females by average +14%, which was equivalent to the effect of mifepristone in virgin females (average +16%). Expression of innate immune response transgenic reporter (Drosocin-GFP) was increased in females mated to wild-type males, and this expression was reduced by mifepristone. In contrast, SP-null males did not increase Drosocin-GFP reporter expression in the female. Similarly, mating increased endogenous microbial load, and this effect was reduced or absent in females fed mifepristone and in females mated to SP-null males; no loss of intestinal barrier integrity was detected using dye-leakage assay. Reduction of microbial load by treating adult flies with doxycycline reduced the effects of both mating and mifepristone on life span. Finally, mifepristone blocked the negative effect on life span caused by transgenic expression of SP in virgin females. The data support the conclusion that the majority of the life span-shortening, immune-suppressive and pro-inflammatory effects of mating are due to male SP, and demonstrate that mifepristone acts in females to counteract these effects of male SP.
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DOI：
10.1073/pnas.0702726104
发表时间：
2007-05-15
影响因子：
11.1
作者：
Ja, William W.;Carvalho, Gil B.;Benzer, Seymour
通讯作者：
Benzer, Seymour
DOI：
10.1073/pnas.1631700100
发表时间：
2003-08-19
影响因子：
11.1
作者：
Liu, HF;Kubli, E
通讯作者：
Kubli, E
影响因子：
3.3
作者：
Fricke C;Green D;Smith D;Dalmay T;Chapman T
通讯作者：
Chapman T
影响因子：
4.5
作者：
Ameku T;Niwa R
通讯作者：
Niwa R
影响因子：
8.8
作者：
Clark RI;Salazar A;Yamada R;Fitz-Gibbon S;Morselli M;Alcaraz J;Rana A;Rera M;Pellegrini M;Ja WW;Walker DW
通讯作者：
Walker DW