Department of Neurology, The Second People's Hospital of Huai'an, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, China.
Department of Dermatology, The Affiliated Children's Hospital of Nanjing Medical University, Nanjing, China.
Toxicol In Vitro. 2018 Aug;50:373-382. doi: 10.1016/j.tiv.2018.04.005. Epub 2018 Apr 14.
There is evidence to support that ROSs are increased in Parkinson's disease (PD). Our recent research showed that angiotensin II (Ang II) participated in the pathogenesis of PD by triggering oxidative stress. Angiotensin-(1-7)[Ang-(1-7)] has been shown to moderate the adverse effects of the Ang II in many diseases. The purpose of the present study was to determine whether the Ang-(1-7) could have similar effects in CATH.a neurons. We used rotenone-induced neuron injury models to evaluate changes in cultured CATH.a cell lines levels of SOD, GSH and ROS. We also evaluated the expression of AT, AT, Mas receptors and Nox1, Nox2, P47, Hsp70 in treated with PBS, rotenone, Ang-(1-7), or Mas receptor antagonist A-779, alone and combined. The qRT-PCR and western blot were used to detect mRNA and protein levels of the AT, AT, Mas receptors and Nox1, Nox2, P47, Hsp70. The levels of SOD and GSH were determined by using commercial kits. The ROS generation was measured by the fluorescent probe assay. Ang-(1-7) in our current study significantly decreased rotenone-induced oxidative damage and increased the SOD and GSH generation. In addition, Ang-(1-7) significantly elevated Mas receptor expression and reduced NADPH oxidase activation, and these effects were completely eliminated by the A-779. Our findings suggest that Ang-(1-7) attenuates rotenone-induced oxidative damage in CATH.a neurons by activating the Mas receptor expression and inhibiting NADPH oxidase.
有证据表明，活性氧（ROS）在帕金森病（PD）中增加。我们最近的研究表明，血管紧张素 II（Ang II）通过触发氧化应激参与 PD 的发病机制。血管紧张素-(1-7)[Ang-(1-7)]已被证明在许多疾病中可以调节 Ang II 的不利影响。本研究的目的是确定 Ang-(1-7)是否对 CATH.a 神经元具有类似的作用。我们使用鱼藤酮诱导的神经元损伤模型来评估培养的 CATH.a 细胞系中 SOD、GSH 和 ROS 水平的变化。我们还评估了单独和联合用 PBS、鱼藤酮、Ang-(1-7)或 Mas 受体拮抗剂 A-779 处理后 AT、AT、Mas 受体和 Nox1、Nox2、P47、Hsp70 的表达。qRT-PCR 和 Western blot 用于检测 AT、AT、Mas 受体和 Nox1、Nox2、P47、Hsp70 的 mRNA 和蛋白水平。使用商业试剂盒测定 SOD 和 GSH 水平。通过荧光探针测定法测量 ROS 的产生。在我们的研究中，Ang-(1-7)显著降低了鱼藤酮诱导的氧化损伤，增加了 SOD 和 GSH 的产生。此外，Ang-(1-7)显著增加了 Mas 受体的表达并减少了 NADPH 氧化酶的激活，而这些作用完全被 A-779 消除。我们的研究结果表明，Ang-(1-7)通过激活 Mas 受体表达和抑制 NADPH 氧化酶来减轻 CATH.a 神经元中的鱼藤酮诱导的氧化损伤。
