Project/Area Number |
09460051
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
応用微生物学・応用生物化学
|
Research Institution | KYUSHU UNIVERSITY |
Principal Investigator |
ITO Makoto Kyushu University, Agriculture, Associate Professor, 農学部, 助教授 (40253512)
|
Co-Investigator(Kenkyū-buntansha) |
HIGASHI Hideyoshi Mitsubishi Kasei Institute of Life Sciences, Senior researcher, 生命科学研究所, 主任研究員
沖野 望 九州大学, 大学院・農学研究科, 日本学術振興会特別研
|
Project Period (FY) |
1997 – 1998
|
Project Status |
Completed (Fiscal Year 1998)
|
Budget Amount *help |
¥13,800,000 (Direct Cost: ¥13,800,000)
Fiscal Year 1998: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 1997: ¥9,200,000 (Direct Cost: ¥9,200,000)
|
Keywords | sphingolipid / lyso-sphingolipid / SCDase / apoptosis / neuron / ganglioside / sphingolipidosis / caspase / ガグクオシド / Neuro.Zo / 加水分解の逆反応(縮合反応) / 遺伝子クローニング / リゾスフィンゴミエリン / 糖脂質の脂質工学 |
Research Abstract |
Sphingosylphosphorylcholine, lyso-GM1 and lyso-GM2, all of which are Mdeacylated derivative of the parental sphingolipids, were known to accumulate in the brain of neuropathic sphingolipidosis patients of Niemann-Pick disease type A, GM1 gangliosidosis, Tay-Sachs and Sandhoff diseases, respectively. This study described that these lysosphingolipids can induce apoptosis in mouse neuroblastoma Neuro2a. Lysosphingolipids, prepared by enzymatic N-deacylation of sphingolipids by SCDase, inhibited [^3H]thymidine incorporation of these cells in a dose dependentmanner, while the parental sphingolipids had no effect. It was revealed that the lysosphingolipid-dependent inhibition of mitogenesis was not due to the differentiation but to the induction of apoptosis of the cells. When Neuro2a cells were cultured with 40-80 muM lysosphingolipids for 48 h, intranucleosomal DNA fragmentation and chromatin condensation were observed. These results may support an idea that lyso-sphingolipids are candidate for etiologic factors of sphingolipidosis.
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