Adropin Is a Key Mediator of Hypoxia Induced Anti-Dipsogenic Effects via TRPV4-CamKK-AMPK Signaling in the Circumventricular Organs of Rats.
Adropin Is a Key Mediator of Hypoxia Induced Anti-Dipsogenic Effects via TRPV4-CamKK-AMPK Signaling in the Circumventricular Organs of Rats.
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Adropin 是大鼠室周器官中缺氧诱导的通过 TRPV4-CamKK-AMPK 信号转导的抗迪作用的关键介质
DOI：
10.3389/fnmol.2017.00105
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发表时间：
2017
影响因子：
4.8
通讯作者：
Huang QY
中科院分区：
文献类型：
--
作者：
Yang F;Zhou L;Qian X;Wang D;He WJ;Tang ZW;Yin J;Huang QY
缺氧条件下水摄入量减少（抗体力作用）已得到充分证实，但根本原因仍不清楚。我们之前的报告表明，SFO 中激活的 TRPV4 神经元与缺氧条件下的抗体力作用相关。虽然低血氧分压直接激活TRPV4，但体液因素也可能参与其中。在本研究中，我们假设阿滴肽（一种新的内源性肽激素）在缺氧早期随着水摄入量的减少而迅速增加（血清和大脑）。此外，c-Fos（与水消耗相关的神经元激活标志物）（SFO 和 MnPO）的核表达也受到抑制。这些影响可以通过一种清道夫——大鼠adropin中和抗体来减轻，该抗体可以在缺氧条件下有效地中和adropin。有趣的是，在大鼠第三脑室注射重组adropin也引发了抗dipogenic作用并减少了SFO中的c-Fos阳性细胞，但当TRPV4被shRNA敲低时，这些作用就不存在了。此外，常氧条件下，adropin 激活的 CamKK-AMPK 信号与 SFO 中的 TRPV4 钙通道相关。这些结果表明，解离性 adropin 在急性缺氧时升高，通过改变 SFO 中的 TRPV4-CamKK-AMPK 信号传导来发挥抗促动力作用。
Water intake reduction (anti-dipsogenic effects) under hypoxia has been well established, but the underlying reason remains unknown. Our previous report indicated that activated TRPV4 neurons in SFO are associated with anti-dipsogenic effects under hypoxia. Although low partial pressure of blood oxygen directly activates TRPV4, humoral factors could also be involved. In the present study, we hypothesize that adropin, a new endogenous peptide hormone, was rapidly increased (serum and brain) concomitant with reduced water intake in early hypoxia. Also, the nuclear expression of c-Fos, a marker for neuronal activation, related to water-consumption (SFO and MnPO) was inhibited. These effects were mitigated by a scavenger, rat adropin neutralizing antibody, which effectively neutralized adropin under hypoxia. Interestingly, injection of recombinant adropin in the third ventricle of the rats also triggered anti-dipsogenic effects and reduced c-Fos positive cells in SFO, but these effects were absent when TRPV4 was knocked down by shRNA. Moreover, adropin-activated CamKK-AMPK signaling related to TRPV4 calcium channel in SFO in normoxia. These results revealed that dissociative adropin was elevated in acute hypoxia, which was responsible for anti-dipsogenic effects by altering TRPV4-CamKK-AMPK signaling in SFO.