Function of oxidative stress in the regulation of hematopoietic stem cell-niche interaction

Kentaro Hosokawa, Fumio Arai, Hiroki Yoshihara, Yuka Nakamura, Yumiko Gomei, Hiroko Iwasaki, Kana Miyamoto, Haruko Shima, Keisuke Ito, Toshio Suda

Research output: Contribution to journalArticle

91 Scopus citations

Abstract

During postnatal life, the bone marrow (BM) supports both self-renewal and differentiation of hematopoietic stem cells (HSCs) in specialized niches, such as osteoblastic niche and vascular niche. A cell adhesion molecule, N-cadherin expressed in the HSCs and osteoblasts, suggesting that homophylic binding of N-cadherin induce the adhesion of HSCs to the niche cells. Here we demonstrate that an anti-cancer drug, 5-fuluorouracil induces reactive oxygen species (ROS) in HSCs, which suppressed N-cadherin expression. These events result in the shift of side population (SP) cells to non-SP cells, indicating that quiescent HSCs are detached from the niche. Administration of a potent anti-oxidant, N-acetyl cystein (NAC) suppressed the shift from SP cells. These data suggest that ROS suppressed the N-cadherin-mediated cell adhesion, and induce the exit of HSCs from the niche.

Original languageEnglish (US)
Pages (from-to)578-583
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume363
Issue number3
DOIs
StatePublished - Nov 23 2007
Externally publishedYes

Keywords

  • Cell adhesion
  • Cell cycle
  • Hematopoietic stem cell
  • N-cadherin
  • Niche
  • Oxidative stress

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Hosokawa, K., Arai, F., Yoshihara, H., Nakamura, Y., Gomei, Y., Iwasaki, H., Miyamoto, K., Shima, H., Ito, K., & Suda, T. (2007). Function of oxidative stress in the regulation of hematopoietic stem cell-niche interaction. Biochemical and Biophysical Research Communications, 363(3), 578-583. https://doi.org/10.1016/j.bbrc.2007.09.014