NADPH oxidase-generated reactive oxygen species in mature follicles are essential for Drosophila ovulation.
NADPH oxidase-generated reactive oxygen species in mature follicles are essential for Drosophila ovulation.
复制标题
DOI：
10.1073/pnas.1800115115
复制
发表时间：
2018-07-24
影响因子：
11.1
通讯作者：
Sun J
中科院分区：
文献类型：
--
作者：
Li W;Young JF;Sun J
活性氧（ROS）在许多病理条件下引起氧化应激和损伤，但它们也可以在生理过程中作为信号分子发挥作用。然而，很难破译ROS来自何处以及哪些ROS参与这些过程。在这篇文章中，我们证明了NADPH氧化酶（NOX）和细胞外超氧化物歧化酶（SOD 3）的功能在果蝇卵室的卵泡细胞产生过氧化氢，调节卵泡破裂和排卵，一个过程中必不可少的生殖。NOX和SOD 3在人类卵泡中表达，可能在人类中发挥类似的作用。因此，我们的工作为治疗ROS相关不孕症或开发新的避孕方法提供了潜在的靶点。卵巢活性氧（ROS）被认为是调节排卵的哺乳动物，但在卵泡中的ROS产生的细节和ROS在排卵中的作用在其他物种仍然是探索不足。在果蝇排卵过程中，成熟卵母细胞周围的后卵泡细胞降解导致卵泡破裂需要基质金属蛋白酶2（MMP 2）。我们最近发现，MMP 2激活和卵泡破裂是由神经元激素章鱼胺（OA）和蘑菇体章鱼胺受体（OAMB）调节的。在目前的研究中，我们研究了超氧化物生成酶NADPH氧化酶（NOX）在果蝇排卵中的作用。我们报告说，氮氧化物是高度富集在成熟的卵泡细胞和氮氧化物敲低这些细胞导致超氧化物的减少和缺陷排卵。与MMP 2活化类似，NOX酶活性也受OA/OAMB-Ca 2+信号通路控制。此外，我们报告说，细胞外超氧化物歧化酶3（SOD 3）需要将超氧化物转化为过氧化氢，这是卵泡破裂的关键信号分子，独立于MMP 2激活。考虑到Nox同源物在哺乳动物卵泡中表达，我们描述的Nox依赖性过氧化氢信号通路可能在其他物种中调节排卵中发挥保守作用。
Reactive oxygen species (ROS) cause oxidative stress and damage in many pathological conditions, but they can also function as signaling molecules in physiological processes. It is difficult, however, to decipher where ROS come from and which ROS are involved in these processes. In this article, we demonstrate that a NADPH oxidase (NOX) and an extracellular superoxide dismutase (SOD3) function in follicle cells of Drosophila egg chambers to produce hydrogen peroxide, which regulates follicle rupture and ovulation, a process essential for reproduction. NOX and SOD3 are expressed in human follicles and could potentially play similar roles in humans. Our work thus provides potential targets for treating ROS-related infertility or developing novel contraceptive approaches. Ovarian reactive oxygen species (ROS) are believed to regulate ovulation in mammals, but the details of ROS production in follicles and the role of ROS in ovulation in other species remain underexplored. In Drosophila ovulation, matrix metalloproteinase 2 (MMP2) is required for follicle rupture by degradation of posterior follicle cells surrounding a mature oocyte. We recently demonstrated that MMP2 activation and follicle rupture are regulated by the neuronal hormone octopamine (OA) and the octopamine receptor in mushroom body (OAMB). In the current study, we investigated the role of the superoxide-generating enzyme NADPH oxidase (NOX) in Drosophila ovulation. We report that Nox is highly enriched in mature follicle cells and that Nox knockdown in these cells leads to a reduction in superoxide and to defective ovulation. Similar to MMP2 activation, NOX enzymatic activity is also controlled by the OA/OAMB-Ca2+ signaling pathway. In addition, we report that extracellular superoxide dismutase 3 (SOD3) is required to convert superoxide to hydrogen peroxide, which acts as the key signaling molecule for follicle rupture, independent of MMP2 activation. Given that Nox homologs are expressed in mammalian follicles, the NOX-dependent hydrogen peroxide signaling pathway that we describe could play a conserved role in regulating ovulation in other species.
登录
查看更多内容
PKCδ和θ可能通过NOX-ROS-TACE级联信号通路介导FSH诱导的小鼠卵母细胞成熟。
影响因子：
3.7
作者：
Chen Q;Zhang W;Ran H;Feng L;Yan H;Mu X;Han Y;Liu W;Xia G;Wang C
通讯作者：
Wang C
DOI：
10.1073/pnas.1614383114
发表时间：
2017-01-24
影响因子：
11.1
作者：
Knapp, Elizabeth;Sun, Jianjun
通讯作者：
Sun, Jianjun
DOI：
10.1073/pnas.252342899
发表时间：
2002-12-10
影响因子：
11.1
作者：
Kirby, K;Hu, JG;Phillips, JP
通讯作者：
Phillips, JP
影响因子：
4.8
作者：
Ho, YS;Gargano, M;Hutz, RJ
通讯作者：
Hutz, RJ
DOI：
10.1016/j.bbapap.2005.05.002
发表时间：
2005-08-01
影响因子：
3.2
作者：
Ohnishi, J;Ohnishi, E;Takahashi, T
通讯作者：
Takahashi, T