| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
Singlet oxygen exerted deteriorating effects on cells and induced cytochrome c (cyt-c) release from mitochondria. Although cyt-c generally induces apoptosis, singlet oxygen suppressed the apoptotic pathway. One reason is that singlet oxygen induced oxidation of cyt-c. Singlet oxygen also inactivated caspases and cathepsins that are involved in the apoptotic pathway.
Although markers for oxidative modification of DNA and lipids are established, there is no proper marker for that of proteins. We examined oxidative products of four amino acids, Trp His, Met, and Tyr, N-formylkynurenine (NFK) was generated from Trp as a major product. Antibody against NFK was raised and found to be reactive to kynurenine, an intermediate of Trp oxidation, as well as NFK. This is the first report on the anti-NFK antibody and could be useful for detection of Trp oxidation and kynurenine in situ. We also established a system to detect glutathionylated proteins using biotinylated GST as a probe, which enabled simple detection of glutathionylated proteins.
We found splenomegaly and anemia in SOD1-deficient mice during long-time breeding of them. In addition, almost all mice developed inflammation in facial skin, which is markedly delayed by administration of an antioxidant, N-acetylcysteine. Primary culture of keratinocytes isolated from neonatal mice indicated the decrease in adhering capability and requirement of serum component for culture. Although only minor phenotype has been reported for SOD1-deficient mice under conventional breeding conditions, long-term observation let us know that SOD1-deficient mice actually show symptoms that are similar to aged mice.
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