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Hypoxia-inducible factor 1 (HIF-1) plays a central role in cellular adaptation to changes in oxygen availability. Recently, prolyl hydroxylation was identified as a key regulatory event that targets the HIF-1alpha subunit for proteasomal degradation via the pVHL ubiquitination complex. In this report, we reveal an important function for ARD1 in mammalian(More)
D-raf, a Drosophila homolog of Raf-1, plays key roles in multiple signal transduction pathways. Dsor1, a putative factor downstream of D-raf, was genetically identified by screening of dominant suppressors of D-raf. Dsor1Su1 mapped on X chromosome significantly suppressed the D-raf mutant phenotypes, and the loss-of-function mutations of Dsor1 showed(More)
The purpose of this paper was to characterize cytochrome P450 (CYP) enzymes involved in N-dealkylation of a new oral erectogenic, DA-8159 to DA-8164, a major circulating active metabolite, in human liver microsomes and to investigate the inhibitory potential of DA-8159 on CYP enzymes. CYP3A4 was identified as the major enzyme responsible for DA-8159(More)
Hypoxia is a well-known signal for angiogenesis, but the recent proposal that hypoxia exists in developing embryonic tissues and that it induces vascular development remains to be proven. In the present study, we demonstrate the presence of hypoxia in normal developing embryos by means of a hypoxia marker, pimonidazole, and its associated antibody. Our data(More)
Insulin-like growth factor (IGF)-binding protein-4 (IGFBP-4), a consistent inhibitor of IGF action, is subject to proteolytic cleavage by the IGF-II-dependent IGFBP-4 protease. However, regulation of the IGF-II-dependent IGFBP-4 protease in vivo is not known. As IGFBP proteases are known to be triggered during pregnancy, we systematically evaluated the(More)
Previous results indicate that ursolic acid (UA), a pentacyclic triterpene acid, has strong cytotoxic activity and effectively induces growth arrest in a variety of systems. However, the molecular mechanisms underlying anti-tumorigenic or chemopreventive activities of UA are poorly understood. To further determine the mechanism of UA, we investigated the(More)
The structural, physicochemical, and biological properties of sulfated oat beta-glucan were characterized. The degree of substitution of the sulfated oat-beta glucan was obtained by elemental analysis, which was 0.68. Compared to native oat beta-glucan, the FT-IR spectra of the derivative showed two new absorption bands at 1250 and 810 cm(-)(1), which would(More)
The Drosophila raf (D-raf) gene promoter contains a recognition consensus sequence for Drosophila STAT (D-STAT). By band mobility shift assay, we detected a factor binding to the D-STAT-recognition sequence in extracts of cultured Drosophila cells treated with vanadate peroxide. UV-cross-linking analyses suggested the size of the binding factor to be almost(More)
It has been proposed that uric acid is an important scavenger of deleterious oxygen species and peroxynitrite in biological systems. The cellular sources responsible for the generation of damage-causing reactive oxygen species (ROS) are widespread. Xanthine dehydrogenase (XDH) / oxidase (XOD) catalyzes the oxidation of xanthine to uric acid. The rosy (ry)(More)
One of the potential causes of age-related neuronal damage can be reactive oxygen species (ROS), as the brain is particularly sensitive to oxidative damage. In the present study, we investigated the effects of aging and dietary restriction (DR) on ROS generation, lipid peroxidation, and antioxidant enzymes in cerebrum, hippocampus, and cerebellum of 6-,(More)