Salvianolic acid B protects human endothelial progenitor cells against oxidative stress-mediated dysfunction by modulating Akt/mTOR/4EBP1, p38 MAPK/ATF2, and ERK1/2 signaling pathways
Salvianolic acid B protects human endothelial progenitor cells against oxidative stress-mediated dysfunction by modulating Akt/mTOR/4EBP1, p38 MAPK/ATF2, and ERK1/2 signaling pathways
复制标题
DOI：
10.1016/j.bcp.2014.04.008
复制
发表时间：
2014-07-01
影响因子：
5.8
通讯作者：
Stiehler, Maik
中科院分区：
文献类型：
--
作者：
Tang, Yubo;Jacobi, Angela;Stiehler, Maik
血管内皮对氧化应激特别敏感，这是在大多数心血管疾病和病症中导致广泛内皮功能障碍的机制之一。通过抗氧化机制防止活性氧（ROS）介导的氧化损伤对于组织维护至关重要，并且对患有心血管和代谢疾病的患者显示出治疗潜力。丹酚酸 B (SalB) 是一种传统中药中的天然生物活性成分，据报道可对多种类型的细胞发挥细胞保护作用。然而，所涉及的潜在机制尚未完全了解。在这里，我们发现 SalB 在体外显着促进人骨髓源性内皮祖细胞 (BM-EPC) 的迁移和管形成能力，并显着消除过氧化氢 (H2O2) 诱导的细胞损伤。 SalB 在 H2O2 诱导后下调 Nox4 和 eNOS 以及烟酰胺腺嘌呤二核苷酸磷酸 (NADPH) 氧化酶的表达，从而防止氧化诱导的内皮功能障碍。此外，SalB 抑制 H2O2 诱导后的 Bax/Bcl-xL 比率和 caspase-3 活化。此外，我们的结果提供了机制证据，表明 mTOR/p70S6K/4EBP1 通路的激活是 SalB 介导的血管生成和针对 BM-EPC 中氧化应激诱导的细胞损伤的保护作用所必需的。 SalB 抑制 MKK3/6-p38 MAPK-ATF2 和 ERK1/2 信号通路，通过降低细胞内 ROS 水平和细胞凋亡，显着保护 BM-EPC 免受氧化应激引起的细胞损伤。总之，通过提供 SalB 对 BM-EPC 氧化还原状态调节的机制见解，我们认为 SalB 具有成为新型促血管生成和细胞保护治疗剂的强大潜力，可应用于内皮损伤介导的血管疾病领域。 (C) 2014 Elsevier Inc. 保留所有权利。
The vascular endothelium is specifically sensitive to oxidative stress, and this is one of the mechanisms that causes widespread endothelial dysfunction in most cardiovascular diseases and disorders. Protection against reactive oxygen species (ROS)-mediated oxidative damage via antioxidant mechanisms is essential for tissue maintenance and shows therapeutic potential for patients suffering from cardiovascular and metabolic disorders. Salvianolic acid B (SalB), a natural bioactive component known from Traditional Chinese Medicine, has been reported to exert cellular protection in various types of cells. However, the underlying mechanisms involved are not fully understood. Here, we showed that SalB significantly promoted the migratory and tube formation abilities of human bone marrow derivedendothelial progenitor cells (BM-EPCs) in vitro, and substantially abrogated hydrogen peroxide (H2O2)induced cell damage. SalB down-regulated Nox4 and eNOS, as well as nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase expression upon H2O2 induction that in turn prevents oxidative-induced endothelial dysfunction. Moreover, SalB suppressed the Bax/Bcl-xL ratio and caspase-3 activation after H2O2 induction. Furthermore, our results provide mechanistic evidence that activation of the mTOR/p70S6K/4EBP1 pathways is required for both SalB-mediated angiogenic and protective effects against oxidative stress-induced cell injury in BM-EPCs. Suppression of MKK3/6-p38 MAPK-ATF2 and ERK1/2 signaling pathways by SalB significantly protected BM-EPCs against cell injury caused by oxidative stress via reduction of intracellular ROS levels and apoptosis. Taken together, by providing a mechanistic insight into the modulation of redox states in BM-EPCs by SalB, we suggest that SalB has a strong potential of being a new proangiogenic and cytoprotective therapeutic agent with applications in the field of endothelial injury-mediated vascular diseases. (C) 2014 Elsevier Inc. All rights reserved.