title: The novel antioxidant TA293 reveals the role of cytoplasmic hydroxyl radicals in oxidative stress-induced senescence and inflammation.
abstract: The hydroxyl radical (OH) possesses the strongest oxidation potential among reactive oxygen species (ROS). Hydroxyl radicals react nonpreferentially with proteins, lipids, and nucleic acids. Additionally, mitochondrial localization of OH causes dysfunction in the mitochondria. The cytoplasmic targets of OH-induced oxidation are unknown. No cytoplasm-specific OH scavenger is available; thus, elucidating the cytoplasmic targets of OH-induced oxidation has proven difficult. Accordingly, we developed a cytoplasm-specific OH-targeted scavenger, TA293, and a mitochondrion-specific scavenger, mitoTA293. Both TA293 and mitoTA293 scavenged OH but not O2-or H2O2. We then examined the intracellular localization of both scavengers in vitro and in vivo. TA293 scavenged pyocyanin-induced cytoplasmic OH but not antimycin A-induced mitochondrial oxidation. mitoTA293 scavenged antimycin A-induced mitochondrial OH but not cytoplasmic OH. TA293 but not mitoTA293 suppressed pyocyanin-induced oxidative damage in the lungs and kidneys of mice. Additionally, TA293 suppressed the expression of inflammatory signaling pathway components and mediators and suppressed OH-induced cellular senescence and apoptosis. These data suggested that TA293 could be used as a novel tool for studying the effects of hydroxyl radical damage within the cytoplasm.
authors.affiliation: Laboratory of Cell Physiology and Chemistry, Faculty of Pharmacy, Takasaki University of Health and Welfare, 60 Nakaorui-machi, Takasaki, Gunma 370-0033, Japan. Electronic address: sakai@takasaki-u.ac.jp.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Sakai
authors.affiliation: Laboratory of Cell Physiology and Chemistry, Faculty of Pharmacy, Takasaki University of Health and Welfare, 60 Nakaorui-machi, Takasaki, Gunma 370-0033, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Imai
authors.affiliation: Graduate School of Science and Engineering, Yamagata University, 4-3-16 Jonan, Yonezawa, Yamagata 992-8510, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Ito
authors.affiliation: Laboratory of Cell Physiology and Chemistry, Faculty of Pharmacy, Takasaki University of Health and Welfare, 60 Nakaorui-machi, Takasaki, Gunma 370-0033, Japan.
authors.forename: Hidetsugu
authors.initials: H
authors.lastname: Takagaki
authors.affiliation: Laboratory of Cell Physiology and Chemistry, Faculty of Pharmacy, Takasaki University of Health and Welfare, 60 Nakaorui-machi, Takasaki, Gunma 370-0033, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Ui
authors.affiliation: Laboratory of Cell Physiology and Chemistry, Faculty of Pharmacy, Takasaki University of Health and Welfare, 60 Nakaorui-machi, Takasaki, Gunma 370-0033, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Hatta
mesh_terms: D000818:Animals; D000968:Antimycin A / Q000737:chemistry; D017209:Apoptosis; D049109:Cell Proliferation; D016922:Cellular Senescence; D003374:Coumarins / Q000737:chemistry*; D003593:Cytoplasm / Q000378:metabolism*; D004578:Electron Spin Resonance Spectroscopy; D005347:Fibroblasts / Q000378:metabolism; D016166:Free Radical Scavengers / Q000737:chemistry*; D017665:Hydroxyl Radical / Q000737:chemistry*; D007249:Inflammation; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism; D018384:Oxidative Stress; D011710:Pyocyanine / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D003374:Coumarins; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; C000619949:TA293 compound; D017665:Hydroxyl Radical; D000968:Antimycin A; D011710:Pyocyanine; D008156:Luciferases
keywords: Antioxidant; Cytoplasmic hydroxyl radicals; Inflammation; Oxidative stress; Senescence