| Project/Area Number |
10680580
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Structural biochemistry
|
|---|
| Research Institution | Kanazawa University |
|---|
Principal Investigator |
HIGUCHI Yoshihiro Kanazawa University Graduate School of Medical Science, 大学院・医学研究科, 助手 (10019630)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
YOSHIMOTO Tanihiro Kanazawa University Graduate School of Medical Science, 大学院・医学系研究科, 教授 (60127876)
|
|---|
| Project Period (FY) |
1998 – 2000
|
| Project Status |
Completed (Fiscal Year 2001)
|
| Budget Amount *help |
¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1999: ¥600,000 (Direct Cost: ¥600,000)
|
|---|
| Keywords | glutathion / glutamate / arachidonic acid / apoptosis / necrosis / glioma cells / lipid peroxidation / giant DNA fragmentation / カスパーゼ-3 / リポオキシゲナーゼ / DNA断片化 / 紫外線 / ポリADPリボースポリメラーゼ / 活性酸素 |
|---|
| Research Abstract |
Glutamate caused GSH depletion inducing apoptosis through endogenously produced active oxygen species and thereby 1-2 Mbp giant DNA and high molecular weight DNA fragmentation prior to the internucleosomal DNA fragmentation seen in C6 rat glioma cells. During apoptosis induced by GSH-depletion, reactive oxygen species (ROS) caused lipid peroxidation associated with PK-C activation. AA promoted cell death by changing the apoptosis to necrosis through lipid peroxidation initiated by lipid hydroperoxides produced by 12-lipoxygenase under the GSH depletion in C6 cells. Some ROS such as hydroperoxide produced by unknown pathway make hydroxy radicals and induce 8-OH-dG formation in the cells. The conversion of apoptosis to necrosis may be a possible event under GSH depleted conditions and a model of glial cell death. GSH depletion caused by glutamate induces 8-OH-dG formation. Polyunsaturated fatty acids enhanced lipid peroxidation associated with 8-OH-dG formation through a chain reaction. BSO, an inhibitor for GSH synthesis, also induced lipid peroxidation and consequently leads to 1-2 Mbp giant DNA fragmentation. Polyunsaturated fatty acids enhanced the giant DNA fragmentation and 3'-OH temini in chromosomal DNA promoting lipid peroxidation by a chain reaction under the GSH depletion induced by both glutamate and BSO. Ultraviolet (UV) radiation activated caspase-3 associated with cleavage of poly (ADP-ribose) polymerase in T-24 carcinoma cells,. UV induced apoptosis through no producing ROS, at least DCFH reactive ROS, activation of caspase-3 and internucleosomal DNA fragmentation. It is suggested that mechanism of cell death on GSH depletion -induced apoptosis is different from that of UV-induced apoptosis.
|
