Cloning and characterization of the rat TIS11 gene |
| |
Authors: | Kaneda Norio Murata Tomiyasu Niimi Yoshiro Minamiyama Makoto |
| |
Institution: | (1) Department of Analytical Neurobiology, Faculty of Pharmacy, Meijo University, Nagoya, 468-8503, Japan;(2) Department of Analytical Neurobiology, Faculty of Pharmacy, Meijo University, Nagoya, 468-8503, Japan;(3) Department of Biochemistry, Nagoya University School of Medicine, Nagoya, 466-8550, Japan |
| |
Abstract: | Pirfenidone (Pf), a new broad-spectrum anti-fibrotic agent, is known to offer protection against lung fibrosis in vivo in laboratory animals, and against mitogenesis and collagen formation by human lung fibroblasts in vitro. Because reactive oxygen species are thought to be involved in these events, we investigated the mechanism(s) by which Pf ameliorates oxidative stress and its effects on NADPH-dependent lipid peroxidation. Pf has been shown to cause inhibit NADPH-dependent lipid peroxidation in sheep liver microsomes in a dose-dependent manner. The concentration of Pf required to cause 50% inhibition of lipid peroxidation was ~ 6 mM. Pf was found to be ineffective as a superoxide radical scavenger. Pf was also ineffective in decomposing H2O2 and chelating iron. In deoxyribose degradation assays, Pf was a potent scavenger of hydroxyl radicals with a rate constant of 5.4 × 109 M-1 sec-1. EPR spectroscopy in combination with spin trapping techniques, using a Fenton type reaction and DMPO as a spin-trapping agent, Pf scavenged hydroxyl radicals in a dose-dependent manner. The concentration of Pf required to inhibit 50% signal height was ~ 2.5 mM. Because iron was used in the Fenton reaction, the ability of Pf in chelating iron was verified in a fluorescent competitive assay using calcein as the fluorescent probe. Pf up to 10 mM concentration was ineffective in chelating either Fe2+ or Fe3+ in this system. We propose that Pf exerts its beneficial effects, at least in part, through its ability to scavenge toxic hydroxyl radicals. |
| |
Keywords: | TIS11 an immediate early gene gene cloning gene expression gene organization promoter |
本文献已被 PubMed SpringerLink 等数据库收录! |
|