Regulation of Neuromodulatory Actions of Angiotensin II in the Brain Neurons by the Ras-Dependent Mitogen-Activated Protein Kinase Pathway
Regulation of Neuromodulatory Actions of Angiotensin II in the Brain Neurons by the Ras-Dependent Mitogen-Activated Protein Kinase Pathway
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Ras 依赖性丝裂原激活蛋白激酶途径对脑神经元血管紧张素 II 神经调节作用的调节
DOI：
10.1523/jneurosci.16-13-04047.1996
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
M. Raizada
中科院分区：
文献类型：
--
作者：
Hong Yang;D. Lu;K. Yu;M. Raizada
血管紧张素 II (Ang II) 刺激神经元中的去甲肾上腺素转运蛋白 (NET) 和酪氨酸羟化酶 (TH)，但这种神经调节的信号转导机制尚不清楚。用 Ang II 处理下丘脑脑干的神经元培养物导致 Ras、Raf-1 和丝裂原激活蛋白激酶的时间和剂量依赖性激活。这种激活是由 Ang II 与 AT1 受体亚型的相互作用介导的，并且与神经元膜上 AT1 受体与 Ras 和 Raf-1 的重新分布有关。使用针对丝裂原激活蛋白激酶的反义寡核苷酸 (AON) 治疗，可将丝裂原激活蛋白激酶的免疫反应性降低 70%，并减弱 Ang II 对 c-fos、NET 和 TH mRNA 水平的刺激。这表明这些基因的诱导需要Ang II 激活丝裂原活化蛋白激酶。相反，AON对丝裂原激活蛋白激酶未能抑制Ang II对纤溶酶原激活剂抑制剂-1 mRNA水平的刺激。这些结果表明，AT1 受体与 Ras-Raf-1 丝裂原激活蛋白激酶信号转导通路偶联，该通路负责刺激 NET 和 TH，这是 Ang II 在大脑中的两种神经调节作用。
Angiotensin II (Ang II) stimulates norepinephrine transporter (NET) and tyrosine hydroxylase (TH) in the neurons, but the signal transduction mechanism of this neuromodulation is not understood. Treatment of neuronal cultures of hypothalamus-brainstem with Ang II resulted in a time- and dose-dependent activation of Ras, Raf-1, and mitogen-activated protein kinase. This activation was mediated by the interaction of Ang II with the AT1 receptor subtype and was associated with the redistribution of AT1 receptor with Ras and Raf-1 on the neuronal membrane. Treatment with antisense oligonucleotide (AON) to mitogen-activated protein kinase decreased mitogen-activated protein kinase immunoreactivity by 70% and attenuated Ang II stimulation of c-fos, NET, and TH mRNA levels. This demonstrates that induction of these genes requires mitogen-activated protein kinase activation by Ang II. In contrast, AON to mitogen-activated protein kinase failed to inhibit Ang II stimulation of plasminogen activator inhibitor-1 mRNA levels. These results suggest that AT1 receptors are coupled to a Ras-Raf-1 mitogen-activated protein kinase signal transduction pathway that is responsible for stimulation of NET and TH, two neuromodulatory actions of Ang II in the brain.
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DOI：
10.1073/pnas.92.4.1162
发表时间：
1995-02
影响因子：
11.1
作者：
D. Lu;K. Yu;M. Raizada
通讯作者：
D. Lu;K. Yu;M. Raizada
DOI：
10.1073/pnas.92.7.2914
发表时间：
1995-03-28
影响因子：
11.1
作者：
LU, D;RAIZADA, MK
通讯作者：
RAIZADA, MK
影响因子：
56.9
作者：
MOODIE, SA;WILLUMSEN, BM;WOLFMAN, A
通讯作者：
WOLFMAN, A
血管紧张素 II 诱导新生大鼠心脏成纤维细胞中蛋白酪氨酸磷酸化。
DOI：
--
发表时间：
1994
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Schorb,W;Peeler,TC;Madigan,NN;Conrad,KM;Baker,KM
通讯作者：
Baker,KM
DOI：
10.1016/s0021-9258(18)82362-6
发表时间：
1993-07
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
R. Davis
通讯作者：
R. Davis