| Budget Amount *help |
¥11,900,000 (Direct Cost: ¥11,900,000)
Fiscal Year 2004: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2003: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥5,600,000 (Direct Cost: ¥5,600,000)
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| Research Abstract |
We found that reactive oxygen (ROS) and nitrogen species (NOx) play important roles in the regulation of circulation, energy metabolism, defence against pathogens, regulation of development and remodeling of tissues in mammals and that this super system is widely preserved among various species. The aim of the present work is to elucidate the full scope of this super system and to establish new strategy by which various diseases including cancer could be prevented and/or treated successfully.
We succeeded to establish the system for the analysis and control of unstable reactive oxygen and nitrogen species in vivo. For example, enzymes, such as SOD, ascorvate oxidase, and cytochrome c were chemically modified to obtain proteinacious probes that can be selectively targeted to ischemic tissues, vascular endothelial cells, hepatocytes, renal proximal tubule cells, and reticuloendothelial cells and tissues. Using these site-directed protein probes, we successfully revealed that the super-system driven by ROS and NOx cooperatively regulates the circulation and mitochondrial energy production, and plays critical roles in the etiology of hypertension and shock. We also succeeded to control mitochondria-dependent apoptosis of a wide variety of cells in vitro and in vivo. We also analized the mechanism of metamorphosis of tadopoles, beatles and of silk worms and fund that the super-system also operates in the regulation of their metamorphosis.
Based on these information, we succeeded to control the time and velocity of apoptosis of various cells in a wide variety of animals including rodents. We also found that L-carnitine which inhibits the mitochondria-dependent apoptosis of cells successfully suppressed the occurrence of degeneration of motor neurons and skeletal muscle in mutant SOD-expressing transgenic mice, an animal model of familiar amyotropic lateral sclerosis.
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