Activation of Orexin System Stimulates CaMKII Expression.
Activation of Orexin System Stimulates CaMKII Expression.
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食欲素系统的激活刺激 CaMKII 表达
DOI：
10.3389/fphys.2021.698185
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发表时间：
2021
影响因子：
4
通讯作者：
Shan Z
中科院分区：
文献类型：
--
作者：
Fan Y;Jiang E;Gao H;Bigalke J;Chen B;Yu C;Chen Q;Shan Z
在啮齿动物中，室旁核（PVN）内食欲素系统的过度活跃已被证明有助于增加交感神经活动（SNA）和血压（BP）。然而，潜在的分子机制尚不清楚。在这里，我们验证了食欲素系统激活刺激钙/钙调素依赖性激酶II （CaMKII）表达和激活的假设，以及CaMKII表达PVN神经元的刺激增加SNA和BP。采用Real-time PCR和/或western blot检测orexin- a给药对正常SD大鼠PVN和表达orexin受体1 （OX1R）的PC12细胞CaMKII表达的影响。采用免疫染色法评估OX1R细胞在SD大鼠PVN中的定位，以及食欲素- a对培养下丘脑神经元CaMKII激活的影响。采用体内交感神经记录，检测光遗传刺激表达camkii的PVN神经元对肾SNA （RSNA）和血压的影响。结果显示，SD大鼠脑室内注射食欲素a可增加PVN中CaMKII亚基mRNA的表达。此外，Orexin-A处理增加了表达ox1r的PC12细胞中CaMKII的表达及其磷酸化。此外，Orexin-A处理增加了新生SD大鼠培养下丘脑神经元CaMKII的激活。最后，光遗传刺激PVN camkii表达神经元导致SD大鼠RSNA和BP显著升高。我们的研究结果表明，食欲素系统活性的增加激活了CaMKII在心血管相关区域的表达，这可能与CaMKII的下游心血管作用有关。
Hyperactivity of the orexin system within the paraventricular nucleus (PVN) has been shown to contribute to increased sympathetic nerve activity (SNA) and blood pressure (BP) in rodent animals. However, the underlying molecular mechanisms remain unclear. Here, we test the hypothesis that orexin system activation stimulates calcium/calmodulin-dependent kinase II (CaMKII) expression and activation, and stimulation of CaMKII expressing PVN neurons increases SNA and BP. Real-time PCR and/or western blot were carried out to test the effect of orexin-A administration on CaMKII expression in the PVN of normal Sprague Dawley (SD) rats and orexin receptor 1 (OX1R) expressing PC12 cells. Immunostaining was performed to assess OX1R cellular localization in the PVN of SD rats as well as orexin-A treatment on CaMKII activation in cultured hypothalamic neurons. In vivo sympathetic nerve recordings were employed to test the impact of optogenetic stimulation of CaMKII-expressing PVN neurons on the renal SNA (RSNA) and BP. The results showed that intracerebroventricular injection of orexin-A into the SD rat increases mRNA expression of CaMKII subunits in the PVN. In addition, Orexin-A treatment increases CaMKII expression and its phosphorylation in OX1R-expressing PC12 cells. Furthermore, Orexin-A treatment increases CaMKII activation in cultured hypothalamic neurons from neonatal SD rats. Finally, optogenetic excitation of PVN CaMKII-expressing neurons results in robust increases in RSNA and BP in SD rats. Our results suggest that increased orexin system activity activates CaMKII expression in cardiovascular relevant regions, and this may be relevant to the downstream cardiovascular effects of CaMKII.
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影响因子：
5.3
作者：
Li, De-Pei;Zhou, Jing-Jing;Pan, Hui-Lin
通讯作者：
Pan, Hui-Lin
DOI：
10.1111/apha.12963
发表时间：
2018-03
期刊：
Acta physiologica (Oxford, England)
影响因子：
--
作者：
Fan Y;Jiang E;Hahka T;Chen QH;Yan J;Shan Z
通讯作者：
Shan Z
DOI：
10.1152/ajpregu.1999.277.6.r1780
发表时间：
1999-12-01
影响因子：
2.8
作者：
Shirasaka, T;Nakazato, M;Kannan, H
通讯作者：
Kannan, H
DOI：
10.1152/ajpheart.00822.2016
发表时间：
2017-12-01
影响因子：
4.8
作者：
Huber, Michael J.;Fan, Yuanyuan;Shan, Zhiying
通讯作者：
Shan, Zhiying
影响因子：
64.8
作者：
Harris, GC;Wimmer, M;Aston-Jones, G
通讯作者：
Aston-Jones, G