Analyses of neuronal apoptosis inhibitory proteins and high-density culture sensitive genes
| Project/Area Number |
09470525
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Nagasaki University |
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Principal Investigator |
UEDA Hiroshi Nagasaki University School of Ph armaceutical Sciences Departmrent of Mo lecular Pharmacology and Neuroscience P rofessor, 薬学部, 教授 (00145674)
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| Co-Investigator(Kenkyū-buntansha) |
TOKUAMA Shogo Nagasaki University School of Pharmaceutical Sciences Department of Molecular Ph, 薬学部, 助手 (70225358)
YOSHIDA Akira Nagasaki University School of Pharmaceutical Sciences Department of Molecular Ph, 薬学部, 助教授 (70257187)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥12,900,000 (Direct Cost: ¥12,900,000)
Fiscal Year 1998: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1997: ¥11,200,000 (Direct Cost: ¥11,200,000)
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| Keywords | neuronal cell death / primary culture / phospholipase C / protein kinase C / cell density / survival factor / アポトーシス / 細胞内情報伝達 / アンチセンス / キナーゼ / 自己リン酸化 |
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| Research Abstract |
We identified the apoptosis-inhibitory factors (AIFs) secreted from serum-free culture of cortical neurons. The cell death in low-density culture of the cortex of rat embryos was suppressed by the addition of conditioned medium (CM) from high-density cultures. We purified such AlEs, AIE-20 and AIF-22 and revealed that these two factors were active in suppressing the apoptosis through protein kinase C mechanisms. Such apoptosis-inhibitory activity was specific for rat cortical neurons, but not for dorsal root ganglion neurons or PC12 pheochromocytoma cells. Furthermore, various known (neuro) trophic factors had no effects in the present culture system under the serum-free condition. These findings suggest that AIF-20 and AIF-22 are both novel autocrine or paracrine type of trophic factors acting through protein kinase C mechanisms for cortical neurons. On the other hand, we cloned high-density culture specific genes, HDSI and HDS2. The survival activity was suppressed by addtion of HDS1 antisense oligonucleotides to the high-density culture and was enhanced by addition of a herpesvirus vector for expressing HDS1 to the low-density culture. These data suggest that the HDS1 is involved in the density-dependent survival action.
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Report
(3 results)
Research Products
(11 results)
