2004 Fiscal Year Final Research Report Summary
Anamorsin, anti-apoptotic molecule, and hematopoiesis
| Project/Area Number |
15591006
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Hematology
|
|---|
| Research Institution | Osaka University |
|---|
Principal Investigator |
SHIBAYAMA Hirohiko Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (60346202)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KANAKURA Yuzuru Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (20177489)
MATSUMURA Itaru Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (00294083)
MIZUKI Masao Osaka University, Graduate School of Medicine, Lecturer, 医学系研究科, 講師 (80283761)
|
|---|
| Project Period (FY) |
2003 – 2004
|
| Keywords | Anamorsin / anti-apoptosis / definitive hematopoiesis / knock-out mouse / DNA microarray / Bcl-xL / Jak2 |
|---|
| Research Abstract |
Many growth factors and cytokines prevent apoptosis. Using an expression cloning method, we identified a novel antiapoptotic molecule named Anamorsin, which does not show any homology to Down apoptosis regulatory molecules such as Bcl-2 family, caspase family, or signal transduction molecules. The expression of Anamorsin was completely dependent on stimulation with growth factors, such as interleukin 3, stem cell factor, and thrombopoietin in factor-dependent hematopoietic cell lines, and forced expression of Anamorsin conferred resistance to apoptosis caused by growth factor deprivation in vitro. Furthermore, Anamorsin was found to act as an antiapoptotic molecule in vivo because Anamorsin -/- mice die in late gestation due to defective definitive hematopoiesis in the fetal liver (FL). Although the number of hematopoietic stem/progenitor cells in the FL did not decrease in these mice, myeloid, and particularly erythroid colony formation in response to cytokines, was severely disrupted. Also, Anamorsin -/- erythroid cells initiated apoptosis during terminal maturation. As for the mechanism of Anamorsin-mediated cell survival, a microarray analysis revealed that the expression of Bcl-xL and Jak2 was severely impaired in the FL of Anamorsin -/- mice. Thus, Anamorsin is considered to be a necessary molecule for hematopoiesis that mediates antiapoptotic effects of various cytokies.
|
Research Products
(12 results)
