title: Vam3 ameliorates total body irradiation-induced hematopoietic system injury partly by regulating the expression of Nrf2-targeted genes.
abstract: 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.
authors.affiliation: 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.
authors.forename: Junling
authors.initials: J
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Xue
authors.affiliation: 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.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Han
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Chunsuo
authors.initials: C
authors.lastname: Yao
authors.affiliation: 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.
authors.forename: Lu
authors.initials: L
authors.lastname: Lu
authors.affiliation: 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.
authors.forename: Deguan
authors.initials: D
authors.lastname: Li
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. Electronic address: houq@imm.ac.cn.
authors.forename: Qi
authors.initials: Q
authors.lastname: Hou
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300041, China.
authors.forename: Weimin
authors.initials: W
authors.lastname: Miao
authors.affiliation: Institute of Laboratory Animal Science, Peking Union Medical College and Chinese Academy of Medical Science, Beijing 100021, China. Electronic address: ai_min_meng@126.com.
authors.forename: Aimin
authors.initials: A
authors.lastname: Meng
authors.affiliation: 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. Electronic address: fansaijun@irm-cams.ac.cn.
authors.forename: Saijun
authors.initials: S
authors.lastname: Fan
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001572:Benzofurans / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000528:radiation effects; D002454:Cell Differentiation / Q000187:drug effects / Q000528:radiation effects; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D005720:Gamma Rays; D015870:Gene Expression; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000528:radiation effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051267:NF-E2-Related Factor 2 / Q000172:deficiency / Q000235:genetics*; D018384:Oxidative Stress; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology*; D014916:Whole-Body Irradiation
chemical_list: D000975:Antioxidants; D001572:Benzofurans; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D011837:Radiation-Protective Agents; D017382:Reactive Oxygen Species; D013267:Stilbenes; C000598179:Vam3 compound; D019009:Proto-Oncogene Proteins c-kit
keywords: Hematopoietic system; Ionizing irradiation; Nrf2; Reactive oxygen species; Vam3