TY - JOUR
T1 - Function of oxidative stress in the regulation of hematopoietic stem cell-niche interaction
AU - Hosokawa, Kentaro
AU - Arai, Fumio
AU - Yoshihara, Hiroki
AU - Nakamura, Yuka
AU - Gomei, Yumiko
AU - Iwasaki, Hiroko
AU - Miyamoto, Kana
AU - Shima, Haruko
AU - Ito, Keisuke
AU - Suda, Toshio
N1 - Funding Information:
We also thank Ayako Kumakubo and Ayami Ono for technical assistance. This work was supported by a Grant-in-Aid for Specially Promoted Research and a Grant-in-Aid for Young Scientists (A) from The Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan, and by the“High-Tech Research Center” Project for Private Universities: matching fund subsidy from MEXT.
PY - 2007/11/23
Y1 - 2007/11/23
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=34848867521&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34848867521&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2007.09.014
DO - 10.1016/j.bbrc.2007.09.014
M3 - Article
C2 - 17897629
AN - SCOPUS:34848867521
SN - 0006-291X
VL - 363
SP - 578
EP - 583
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -