PMID- 17897629 OWN - NLM STAT- MEDLINE DCOM- 20080211 LR - 20161124 IS - 0006-291X (Print) IS - 0006-291X (Linking) VI - 363 IP - 3 DP - 2007 Nov 23 TI - Function of oxidative stress in the regulation of hematopoietic stem cell-niche interaction. PG - 578-83 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. FAU - Hosokawa, Kentaro AU - Hosokawa K AD - Department of Cell Differentiation, The Sakaguchi Laboratory of Developmental Biology, School of Medicine, Keio University, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582, Japan. FAU - Arai, Fumio AU - Arai F FAU - Yoshihara, Hiroki AU - Yoshihara H FAU - Nakamura, Yuka AU - Nakamura Y FAU - Gomei, Yumiko AU - Gomei Y FAU - Iwasaki, Hiroko AU - Iwasaki H FAU - Miyamoto, Kana AU - Miyamoto K FAU - Shima, Haruko AU - Shima H FAU - Ito, Keisuke AU - Ito K FAU - Suda, Toshio AU - Suda T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070918 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Cadherins) RN - 0 (Enzyme Inhibitors) RN - 0 (Free Radical Scavengers) RN - 0 (Imidazoles) RN - 0 (Pyridines) RN - 0 (RNA, Messenger) RN - 0 (Reactive Oxygen Species) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - OU13V1EYWQ (SB 203580) RN - U3P01618RT (Fluorouracil) RN - WYQ7N0BPYC (Acetylcysteine) SB - IM MH - Acetylcysteine/pharmacology MH - Animals MH - Bone Marrow Cells/cytology/drug effects/metabolism MH - Cadherins/genetics/metabolism MH - Cell Count MH - Cells, Cultured MH - Enzyme Inhibitors/pharmacology MH - Flow Cytometry MH - Fluorouracil/pharmacology MH - Free Radical Scavengers/pharmacology MH - Gene Expression/drug effects MH - Hematopoietic Stem Cells/cytology/drug effects/*metabolism MH - Imidazoles/pharmacology MH - Immunohistochemistry MH - Mice MH - Mice, Inbred C57BL MH - Oxidative Stress/*physiology MH - Pyridines/pharmacology MH - RNA, Messenger/genetics/metabolism MH - Reactive Oxygen Species/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Time Factors MH - p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors/genetics/metabolism EDAT- 2007/09/28 09:00 MHDA- 2008/02/12 09:00 CRDT- 2007/09/28 09:00 PHST- 2007/08/29 00:00 [received] PHST- 2007/09/05 00:00 [accepted] PHST- 2007/09/28 09:00 [pubmed] PHST- 2008/02/12 09:00 [medline] PHST- 2007/09/28 09:00 [entrez] AID - S0006-291X(07)01955-9 [pii] AID - 10.1016/j.bbrc.2007.09.014 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2007 Nov 23;363(3):578-83. doi: 10.1016/j.bbrc.2007.09.014. Epub 2007 Sep 18.