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

K Hosokawa, F Arai, H Yoshihara, Y Nakamura… - Biochemical and …, 2007 - Elsevier
K Hosokawa, F Arai, H Yoshihara, Y Nakamura, Y Gomei, H Iwasaki, K Miyamoto, H Shima…
Biochemical and biophysical research communications, 2007Elsevier
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 …
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.
Elsevier