| Project/Area Number |
08457335
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Digestive surgery
|
|---|
| Research Institution | Kansai Medical University |
|---|
Principal Investigator |
TANAKA Takuya Kansai Medical University, Medical Department, assosiate professor, 医学部, 助教授 (70121952)
|
|---|
| Project Period (FY) |
1996 – 1998
|
| Project Status |
Completed (Fiscal Year 1998)
|
| Budget Amount *help |
¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 1998: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1997: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1996: ¥2,700,000 (Direct Cost: ¥2,700,000)
|
|---|
| Keywords | liver / nitric oxide / oxygen radical / mitochondria / LPS / TNF-a / TNF-^a / LPS / TNF-α / 肝細胞 / 細胞障害性 / 細胞保護性 / SNAP / 活性酸素 / NO / poly(ADP-ribose)polymerase / ミトコンドリア障害 / 細胞障害抑制 |
|---|
| Research Abstract |
'Treatment with the nitric oxide (NO)-generating compound prodtected cultured L929 cells from apoptosis induced by tumor necrosis factor-alpha (TNF-alpha) plus actinoinycin D,as determined by the appearance of a sub-Gl peak caused by extracellular leakage of low molecular weight DNA.NO also prevented TNF-alpha plus actinomycin D-induced enhancement of the production of reactive oxygen intermediates, as assessed by oxidation of both dehydrorhodamine 123 and hydroethidine. Because inhibition of mitochondrial respiration by rotenone or antimycin A suppressed the increase of oxidation of both dihydrorhodamine 123 and hydroethidine, it was suggested that TNF-alpha accelerated the leakage of reactive oxygen intermediates from the mitochondria electron transport system. These findings indicate that decrease mitochondria formation of ractive oxygen intermediates after NO administration might partly prevent TNF-alpha plus actinomycin D induced apoptosis.
The metabolic inhibitor actinomycin D blocked most of the LPS-induced rise of plasma nitrite/nitrate levels, as did administration of a nitric oxide synthase inhibitor which also promoted LPS-induced apoptotic liver damage in vivo. Administration of nitoric oxide donors to mice resulted in elevation of the plasma nitrite/nitrate level and amelioration of actinomycin D/LPS-induced apoptotic liver damage. These results suggested that nitric oxide may regulated programmed cell death in the liver and that induction of genes including inducible nitric oxide synthase plays an important role in protecting the liver against LPS-induced apoptotic damage. This effect appears to be mediated, at least in part, by the soluble guanylate pathway.
|
