Vam3 ameliorates total body irradiation-induced hematopoietic system injury partly by regulating the expression of Nrf2-targeted genes

Free Radic Biol Med. 2016 Dec:101:455-464. doi: 10.1016/j.freeradbiomed.2016.10.501. Epub 2016 Oct 27.

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.

Keywords: Hematopoietic system; Ionizing irradiation; Nrf2; Reactive oxygen species; Vam3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Benzofurans / pharmacology*
  • Bone Marrow Cells / drug effects*
  • Bone Marrow Cells / radiation effects
  • Cell Differentiation / drug effects
  • Cell Differentiation / radiation effects
  • Cell Proliferation / drug effects
  • Cell Proliferation / radiation effects
  • Gamma Rays
  • Gene Expression
  • Hematopoietic Stem Cells / drug effects*
  • Hematopoietic Stem Cells / radiation effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NF-E2-Related Factor 2 / deficiency
  • NF-E2-Related Factor 2 / genetics*
  • Oxidative Stress
  • Proto-Oncogene Proteins c-kit / genetics
  • Proto-Oncogene Proteins c-kit / metabolism
  • Radiation-Protective Agents / pharmacology*
  • Reactive Oxygen Species / agonists
  • Reactive Oxygen Species / antagonists & inhibitors
  • Reactive Oxygen Species / metabolism*
  • Stilbenes / pharmacology*
  • Whole-Body Irradiation

Substances

  • Antioxidants
  • Benzofurans
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • Radiation-Protective Agents
  • Reactive Oxygen Species
  • Stilbenes
  • Vam3 compound
  • Proto-Oncogene Proteins c-kit