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首页> 外文期刊>American Journal of Physiology >Differential expression of neuronal ACE2 in transgenic mice with overexpression of the brain renin-angiotensin system.
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Differential expression of neuronal ACE2 in transgenic mice with overexpression of the brain renin-angiotensin system.

机译：神经元ACE2在具有脑肾素-血管紧张素系统过表达的转基因小鼠中的差异表达。

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摘要

Angiotensin-converting enzyme 2 (ACE2) is a newly discovered carboxy-peptidase responsible for the formation of vasodilatory peptides such as angiotensin-(1-7). We hypothesized that ACE2 is part of the brain renin-angiotensin system, and its expression is regulated by the other elements of this system. ACE2 immunostaining was performed in transgenic mouse brain sections from neuron-specific enolase-AT(1A) (overexpressing AT(1A) receptors), R(+)A(+) (overexpressing angiotensinogen and renin), and control (nontransgenic littermates) mice. Results show that ACE2 staining is widely distributed throughout the brain. Using cell-type-specific antibodies, we observed that ACE2 staining is present in the cytoplasm of neuronal cell bodies but not in glial cells. In the subfornical organ, an area lacking the blood-brain barrier and sensitive to blood-borne angiotensin II, ACE2 was significantly increased in transgenic mice. Interestingly, ACE2 mRNA and protein expression were inversely correlated in the nucleus of tractus solitarius/dorsal motor nucleus of the vagus and the ventrolateral medulla, when comparing transgenic to nontransgenic mice. These results suggest that ACE2 is localized to the cytoplasm of neuronal cells in the brain and that ACE2 levels appear highly regulated by other components of the renin-angiotensin system, confirming its involvement in this system. Moreover, ACE2 expression in brain structures involved in the control of cardiovascular function suggests that the carboxypeptidase may have a role in the central regulation of blood pressure and diseases involving the autonomic nervous system, such as hypertension.
机译：血管紧张素转换酶2（ACE2）是一种新发现的羧基肽酶，负责形成血管扩张肽，如血管紧张素-（1-7）。我们假设ACE2是脑肾素-血管紧张素系统的一部分，其表达受该系统其他元素的调节。 ACE2免疫染色在神经元特异性烯醇酶-AT（1A）（过表达AT（1A）受体），R（+）A（+）（过表达血管紧张素原和肾素）和对照（非转基因同窝动物）小鼠的转基因小鼠脑切片中进行。结果表明，ACE2染色广泛分布于整个大脑。使用细胞类型特异性抗体，我们观察到ACE2染色存在于神经元细胞体的细胞质中，而不存在于神经胶质细胞中。在分部器官中，缺乏血脑屏障并且对血源性血管紧张素II，ACE2敏感的区域在转基因小鼠中显着增加。有趣的是，当将转基因小鼠与非转基因小鼠进行比较时，在迷路的孤线束/背侧运动核中，ACE2 mRNA和蛋白表达呈负相关。这些结果表明，ACE2位于大脑神经元细胞的细胞质中，并且ACE2的水平似乎受到肾素-血管紧张素系统其他成分的高度调节，从而证实了它参与了该系统。此外，参与心血管功能控制的脑部结构中ACE2的表达表明羧肽酶可能在血压的中央调节和涉及自主神经系统的疾病（例如高血压）中发挥作用。

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