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J. Biol. Chem., Vol. 279, Issue 53, 55578-55586, December 31, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/53/55578    most recent M408238200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nakata, S. Articles by Kanakura, Y. Search for Related Content PubMed PubMed Citation Articles by Nakata, S. Articles by Kanakura, Y. Social Bookmarking                      What's this?

NF-B Family Proteins Participate in Multiple Steps of Hematopoiesis through Elimination of Reactive Oxygen Species^*

Soichi Nakata, Itaru Matsumura, Hirokazu Tanaka, Sachiko Ezoe, Yusuke Satoh, Jun Ishikawa, Takumi Era¶, and Yuzuru Kanakura

From the Department of Hematology and Oncology, Osaka University Graduate School of Medicine, 2-2, Yamada-oka, Suita, Osaka 565-0871, Japan and the^¶Stem Cell Biology Group, RIKEN Center for Development Biology, 2-2-3, Minatojima-minami-machi, Tyuo-ku, Kobe City, Hyogo 650-0047, Japan

To examine the roles for NF-B family proteins in hematopoiesis, we first expressed dominant negative Rel/NF-B(IBSR) in a factor-dependent cell line, Ba/F3. Although IBSR neither affected thrombopoietin-dependent nor gp130-mediated growth, it suppressed interleukin-3- and erythropoietin-dependent growth at low concentrations. In addition, IBSR enhanced factor-deprived apoptosis through the accumulation of reactive oxygen species (ROS). When expressed in normal hematopoietic stem/progenitor cells, IBSR induced apoptosis even in the presence of appropriate cytokines by accumulating ROS. We also expressed IBSR in an inducible fashion at various stages of hematopoiesis using the OP9 system, in which hematopoietic cells are induced to develop from embryonic stem cells. When IBSR was expressed at the stage of Flk-1⁺ cells (putative hemangioblasts), IBSR inhibited the development of primitive hematopoietic progenitor cells by inducing apoptosis through the ROS accumulation. Furthermore, when IBSR was expressed after the development of hematopoietic progenitor cells, it inhibited their terminal differentiation toward erythrocytes, megakaryocytes, and granulocytes by inducing apoptosis through the ROS accumulation. These results indicate that NF-B is required for preventing apoptosis at multiple steps of hematopoiesis by eliminating ROS.

Received for publication, July 21, 2004 , and in revised form, September 27, 2004.

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed. Tel.: 81-6-6879-3871; Fax: 81-6-6879-3879; E-mail: matumura{at}bldon.med.osaka-u.ac.jp.

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