Dopamine induces platelet production from megakaryocytes via oxidative stress-mediated signaling pathways
Dopamine induces platelet production from megakaryocytes via oxidative stress-mediated signaling pathways
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DOI：
10.1080/09537104.2017.1356451
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发表时间：
2018-01-01
期刊：
影响因子：
3.3
通讯作者：
Wang, Junping
中科院分区：
文献类型：
--
作者：
Chen, Shilei;Hu, Mengjia;Wang, Junping
多巴胺 (DA) 是一种儿茶酚胺神经递质，因其在造血中的多种作用而闻名，但其在血小板生成中的功能仍知之甚少。这项研究表明，DA 刺激可以通过活性氧 (ROS) 依赖性途径，在血小板生成的最后阶段直接诱导巨核细胞 (MK) 产生血小板。结果表明，DA处理可显着升高MKs中的ROS水平，并随时间依赖性激活氧化应激介导的信号通路，包括p38丝裂原激活蛋白激酶、c-Jun NH2末端激酶和caspase-3信号通路，而抗氧化剂N-乙酰半胱氨酸和L-谷胱甘肽可有效抑制这些信号通路的激活，以及DA引发的ROS增加和血小板生成。因此，我们的数据揭示了DA在血小板生成中的直接作用和机制，这为DA在造血中的功能识别提供了新的见解。
Dopamine (DA), a catecholamine neurotransmitter, is known to for its diverse roles on hematopoiesis, yet its function in thrombopoiesis remains poorly understood. This study shows that DA stimulation can directly induce platelet production from megakaryocytes (MKs) in the final stages of thrombopoiesis via a reactive oxygen species (ROS)-dependent pathway. The mechanism was suggested by the results that DA treatment could significantly elevate the ROS levels in MKs, and time-dependently activate oxidative stress-mediated signaling, including p38 mitogen-activated protein kinase, c-Jun NH2-terminal kinase, and caspase-3 signaling pathways, while the antioxidants N-acetylcysteine and L-glutathione could effectively inhibit the activation of these signaling pathways, as well as the ROS increase and platelet production triggered by DA. Therefore, our data revealed that the direct role and mechanism of DA in thrombopoiesis, which provides new insights into the function recognition of DA in hematopoiesis.