Zhang Junling, Xue Xiaolei, Han Xiaodan, Yao Chunsuo, Lu Lu, Li Deguan, Hou Qi, Miao Weimin, Meng Aimin, Fan Saijun
Tianjin Key Lab of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Peking Union Medical College and Chinese Academy of Medical Science, Tianjin 300192, China.
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Free Radic Biol Med. 2016 Dec;101:455-464. doi: 10.1016/j.freeradbiomed.2016.10.501. Epub 2016 Oct 27.
Vam3, a resveratrol dimer, has been implicated in the regulation of chronic obstructive pulmonary disease. However, the effect of Vam3 on total body irradiation (TBI)-induced hematopoietic progenitor cells (HPCs), and hematopoietic stem cells (HSCs) injury is unknown. In this study, we examined whether Vam3could ameliorate hematopoietic system injury induced by TBI. Our results indicated that Vam3 alleviated TBI-induced injury by improving the self-renewal and differentiation of HPCs, and HSCs. Vam3 decreased the intracellular ROS levels in irradiated mice HPCs/HSCs or c-kit positive cells and inhibited apoptosis and DNA damage in LSKs and HPCs after TBI. Vam3 up-regulated the expression of Nrf2 and related genes and proteins in irradiated c-kit positive cells in vitro. However, Vam3 did not increase the cell viability or the number of CFU-GM c-kit positive cells in irradiated Nrf2 mice but decreased the cellular ROS level. The above data showed that Vam3 ameliorates total body irradiation-induced hematopoietic system injury and that Nrf2 is essential in mediating Vam3's protective effect on the proliferation of c-kit positive cells after irradiation but not its ability to scavenge for free radicals.
白藜芦醇二聚体Vam3与慢性阻塞性肺疾病的调控有关。然而，Vam3对全身照射（TBI）诱导的造血祖细胞（HPCs）和造血干细胞（HSCs）损伤的影响尚不清楚。在本研究中，我们检测了Vam3是否能改善TBI诱导的造血系统损伤。我们的结果表明，Vam3通过改善HPCs和HSCs的自我更新和分化来减轻TBI诱导的损伤。Vam3降低了照射后小鼠HPCs/HSCs或c-kit阳性细胞内的ROS水平，并抑制了TBI后LSKs和HPCs的凋亡和DNA损伤。Vam3在体外上调了照射后c-kit阳性细胞中Nrf2及相关基因和蛋白的表达。然而，Vam3并未增加照射后Nrf2基因敲除小鼠的细胞活力或CFU-GM c-kit阳性细胞数量，但降低了细胞内ROS水平。上述数据表明，Vam3可改善全身照射诱导的造血系统损伤，且Nrf2在介导Vam3对照射后c-kit阳性细胞增殖的保护作用中至关重要，但对其清除自由基的能力并非必需。
