辛二氢异丙烯 B 通过抑制星形胶质细胞中的 HDAC6-NADPH 氧化酶-ROS 轴缓解 HIV-1 Tat 诱导的炎症反应。
Hindsiipropane B alleviates HIV-1 Tat-induced inflammatory responses by suppressing HDAC6-NADPH oxidase-ROS axis in astrocytes.
机构信息
Department of Biomedical Science and Research Institute for Bioscience & Biotechnology, Hallym University, Chunchon 24252, Korea.
Department of Chemistry and Institute of Applied Chemistry, Hallym University, Chunchon 24252, Korea.
出版信息
BMB Rep. 2018 Aug;51(8):394-399. doi: 10.5483/bmbrep.2018.51.8.061.
Human immunodeficiency virus-1 (HIV-1) transactivator of transcription (Tat) is an important viral factor in neuroinflammation. Hindsiipropane B, present in Celastrus hindsii, possesses various biological mechanisms including antiinflammatory activity. In this report, we explored the regulatory activity of hindsiipropane B on HIV-1 Tat-mediated chemokine production and its mode of action in astrocytes. Hindsiipropane B significantly alleviated HIV-1 Tat-mediated production of inflammatory chemokines, CCL2, CXCL8, and CXCL10. Hindsiipropane B inhibited expression of HDAC6, which is important regulator in HIV-1 Tat-mediated chemokine production. Hindsiipropane B diminished HIV-1 Tat-mediated reactive oxygen species (ROS) generation and NADPH oxidase activation/expression. Furthermore, hindsiipropane B inhibited HIV-1 Tat-mediated signaling cascades including MAPK, NF-κB, and AP-1. These data suggest that hindsiipropane B exerts its inhibitory effects on HIV-1 Tat-mediated chemokine production via down-regulating the HDAC6-NADPH oxidase-MAPK-NF-κB/AP-1 signaling axis, and could serve as a therapeutic lead compound against HIV-1 Tat-associated neuroinflammation. [BMB Reports 2018; 51(8): 394-399].
人类免疫缺陷病毒-1（HIV-1）转录激活物（Tat）是神经炎症中的一个重要病毒因子。南蛇藤素 B 存在于南蛇藤中，具有多种生物学机制，包括抗炎活性。在本报告中，我们探讨了 hindsiipropane B 对 HIV-1 Tat 介导的趋化因子产生的调节活性及其在星形胶质细胞中的作用机制。hindsiipropane B 显著减轻了 HIV-1 Tat 介导的炎症趋化因子 CCL2、CXCL8 和 CXCL10 的产生。hindsiipropane B 抑制了 HDAC6 的表达，HDAC6 是 HIV-1 Tat 介导的趋化因子产生的重要调节剂。hindsiipropane B 减少了 HIV-1 Tat 介导的活性氧（ROS）生成和 NADPH 氧化酶激活/表达。此外，hindsiipropane B 抑制了 HIV-1 Tat 介导的信号转导级联，包括 MAPK、NF-κB 和 AP-1。这些数据表明，hindsiipropane B 通过下调 HDAC6-NADPH 氧化酶-MAPK-NF-κB/AP-1 信号轴，发挥其对 HIV-1 Tat 介导的趋化因子产生的抑制作用，可作为一种治疗 HIV-1 Tat 相关神经炎症的先导化合物。[BMB 报告 2018；51(8): 394-399]。
Zotero 插件